Skin and Seborrhea
Generic Name: arsenic trioxide, oyster shell calcium carbonate, crude, graphite, delphinium staphisagria seed and sulfur liquid
Dosage Form: FOR ANIMAL USE ONLY
Skin and Seborrhea
Homeopathic remedy provides relief from the symptoms of skin
conditions causing smelly skin and ears, dull, greasy coat and dandruff.
1-20lbs/5 drops 3 times daily.
21-60lbs/10 drops 3 times daily.
61-100lbs/15 drops 3 times daily.
Over 100lbs/20 drops 3 times daily.
Pets Under 1lb, 2 drops in water 3 times daily.
Remedy may be dosed directly into mouth, on food/treat or in water.
Birds: Add 2 drops to at least 8oz of drinking water daily.
When symptoms improve, reduce dosing to twice daily, then once daily.
When symptoms clear up, discontinue use. If symptoms reappear repeat
the original dose.
Visit www.homeopet.com for detailed dosing and information.
Contact Veterinarian if problems persist.
Ingredients HPUS:
Sulphur, Staphysagria, Calcarea Carbonicum, Graphites, Arsenicum
Album 6c and 30c
Alcohol, Purified Water
Skin and Seborrhea
sulphur, staphysagria, calcarea carbonicum, graphites, arsenicum album liquid Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 61571-557 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ARSENIC TRIOXIDE (ARSENIC TRIOXIDE) ARSENIC TRIOXIDE 6 [hp_C] in 15 mL OYSTER SHELL CALCIUM CARBONATE, CRUDE (OYSTER SHELL CALCIUM CARBONATE, CRUDE) OYSTER SHELL CALCIUM CARBONATE, CRUDE 6 [hp_C] in 15 mL GRAPHITE (GRAPHITE) GRAPHITE 6 [hp_C] in 15 mL DELPHINIUM STAPHISAGRIA SEED (DELPHINIUM STAPHISAGRIA SEED) DELPHINIUM STAPHISAGRIA SEED 6 [hp_C] in 15 mL SULFUR (SULFUR) SULFUR 6 [hp_C] in 15 mL Inactive Ingredients Ingredient Name Strength ALCOHOL WATER Product Characteristics Color Score Shape Size Flavor Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 61571-557-02 15 mL In 1 BOTTLE, DROPPER None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved homeopathic 04/15/1995
Labeler - HomeoPet, LLC (121272657) Registrant - HomeoPet, LLC (121272657) Establishment Name Address ID/FEI Operations Washington Homeopathic Products, Inc. 084929389 manufacture Revised: 09/2010HomeoPet, LLC
Sentry HC Dermasphere Medicated Shampoo
Dosage Form: FOR ANIMAL USE ONLY
Medicated Shampoo For Dogs
Indications and Usage for Sentry HC Dermasphere Medicated Shampoo
Sentry HC Dermasphere Medicated Shampoo For Dogs is an antiseborrheic shampoo that aids in the removal of scales, crust, and excessive skin oil associated with seborrhea and other non-specific skin conditions. Combines the proven benefits of oatmeal, sulfur and salicylic acid. Contains Dermaspheres, a micro encapsulation technology that holds key ingredients in miscroscopic spheres and improves th effectiveness of the shampoo.
SIGNS: Recommended for dogs with oily skin and coat.
Specially formulated for seborrhea and other skin conditions
Medicated Dermaspheres attach to skin and coat and release over time
Aids in the removal of scales, crust and excessive skin oil
DIRECTIONS FOR USE
Shake well before use. Wet the hair coat with warm water. Apply a thin line of shampoo from the base of the neck to the base of the tail. Massage the shampoo into wet hair coat. Rinse and repeat. May be used two to three times a week. Discontinue use and consult a veterinarian if undue skin irritation develops or increases, or if the condition persists or recurs, as symptoms may be indicative of an underlying serious condition.
CAUTION
For Animal Use Only. FOR EXTERNAL USE ONLY. Avoid contact with eyes or mucous membranes. In case of contact, flush eyes with water and seek medical attention if irritation persists.
KEEP OUT OF REACH OF CHILDREN
Warnings
Wash hands after use. In case if accidental ingestion, seek professional assistance or contact a Poison Control Center immediately.
ACTIVE INGREDIENTS
Salicylic Acid 2%, Solubilized Sulfur 2%.
OTHER INGREDIENTS
Water, Sodium Lauryl Sulfate, Lauramide DEA, Glycerin, Colloidal Oatmeal, Dermaspheres, Magnesium Aluminum Silicate, Sodium Hydroxide, Fragrance, Hydroxypropyl Cellulosa, FD and C Blue #1. May also contain sodium chloride and/or sodium hydroxide.
How is Sentry HC Dermasphere Medicated Shampoo Supplied
Net 12 fl oz (354 mL)
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Distributed by: Sergeant's Pet Care Products, Inc., Omaha NE 68130
Made in USA
PATENTED DERMASPHERE TECHNOLOGY
Patent #6,277,404
Sentry HC Dermasphere Medicated Shampoo FOR DOGS
salicylic acid, solubilized sulfur lotion/shampoo
Product Information
Product Type
OTC ANIMAL DRUG
NDC Product Code (Source)
21091-074
Route of Administration
TOPICAL
DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name
Basis of Strength
Strength
SALICYLIC ACID (SALICYLIC ACID)
SALICYLIC ACID
7.08 mL in 354 mL
SULFUR (SULFUR)
SULFUR
7.08 mL in 354 mL
Inactive Ingredients
Ingredient Name
Strength
No Inactive Ingredients Found
Product Characteristics
Color
blue (Aqua Blue)
Score
Shape
Size
Flavor
Imprint Code
Contains
Packaging
#
NDC
Package Description
Multilevel Packaging
1
21091-074-12
354 mL In 1 BOTTLE, PUMP
None
Marketing Information
Marketing Category
Application Number or Monograph Citation
Marketing Start Date
Marketing End Date
unapproved drug other
11/19/2008
Labeler - Sergeant's Pet Care Products, Inc. (876995171)
Revised: 04/2010Sergeant's Pet Care Products, Inc.
Selenium/Urea/Zinc Pyrithione
Pronunciation: se-LEE-nee-um/ue-REE-a/zink PIR-i-THYE-one
Generic Name: Selenium/Urea/Zinc Pyrithione
Brand Name: Examples include Selonos and Selseb
Selenium/Urea/Zinc Pyrithione is used for:
Treating dandruff, seborrhea, or tinea versicolor (a fungal infection). It may also be used for other conditions as determined by your doctor.
Selenium/Urea/Zinc Pyrithione is an antiseborrheic, antifungal medicine. It decreases skin cell growth associated with flaking and itching. It also kills sensitive fungi.
Do NOT use Selenium/Urea/Zinc Pyrithione if: you are allergic to any ingredient in Selenium/Urea/Zinc PyrithioneContact your doctor or health care provider right away if any of these apply to you.
Before using Selenium/Urea/Zinc Pyrithione:Some medical conditions may interact with Selenium/Urea/Zinc Pyrithione. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have broken, irritated, inflamed, or oozing skin at the application siteSome MEDICINES MAY INTERACT with Selenium/Urea/Zinc Pyrithione. Because little, if any, of Selenium/Urea/Zinc Pyrithione is absorbed into the blood, the risk of it interacting with another medicine is low.
Ask your health care provider if Selenium/Urea/Zinc Pyrithione may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Selenium/Urea/Zinc Pyrithione:Use Selenium/Urea/Zinc Pyrithione as directed by your doctor. Check the label on the medicine for exact dosing instructions.
To treat dandruff or seborrhea, massage Selenium/Urea/Zinc Pyrithione into the wet scalp as directed by your doctor. Rinse scalp and hair well after treatment. To treat tinea versicolor, apply a sufficient amount to cover affected areas. Lather well with a small amount of water. Leave the medicine on the skin for 10 minutes, then rinse well. Wash your hands right away after using Selenium/Urea/Zinc Pyrithione, unless your hands are part of the treated area. Continue to use Selenium/Urea/Zinc Pyrithione as directed by your doctor even if your condition begins to improve. Do not miss any doses. If you miss a dose of Selenium/Urea/Zinc Pyrithione, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at onceAsk your health care provider any questions you may have about how to use Selenium/Urea/Zinc Pyrithione.
Important safety information: Selenium/Urea/Zinc Pyrithione is for external use only. Do not get Selenium/Urea/Zinc Pyrithione in your eyes, nose, mouth, or in the genital area. If you get it in any of these areas, rinse right away with cool water. Do not apply Selenium/Urea/Zinc Pyrithione in skin folds; irritation may occur. Do not use Selenium/Urea/Zinc Pyrithione on broken, blistered, or inflamed skin. Do not use more often or for longer than prescribed without checking with your doctor. If you use topical products too often, some conditions may become worse. Do not use Selenium/Urea/Zinc Pyrithione for another skin condition at a later time. Selenium/Urea/Zinc Pyrithione may discolor the hair. This effect can be decreased or avoided by rinsing your hair well after you use Selenium/Urea/Zinc Pyrithione. Selenium/Urea/Zinc Pyrithione may cause your scalp to become dry or oily. If these side effects occur and become bothersome, contact your doctor. Selenium/Urea/Zinc Pyrithione may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away. Selenium/Urea/Zinc Pyrithione should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed. PREGNANCY and BREAST-FEEDING: It is not known if Selenium/Urea/Zinc Pyrithione can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Selenium/Urea/Zinc Pyrithione while you are pregnant. It is not known if Selenium/Urea/Zinc Pyrithione is found in breast milk. If you are or will be breast-feeding while you use Selenium/Urea/Zinc Pyrithione, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Selenium/Urea/Zinc Pyrithione:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
No COMMON side effects have been reported with Selenium/Urea/Zinc Pyrithione.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); severe skin irritation.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Selenium/Urea/Zinc Pyrithione side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Selenium/Urea/Zinc Pyrithione may be harmful if swallowed.
Proper storage of Selenium/Urea/Zinc Pyrithione:Store Selenium/Urea/Zinc Pyrithione at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Do not freeze. Store away from heat and light. Keep Selenium/Urea/Zinc Pyrithione out of the reach of children and away from pets.
General information: If you have any questions about Selenium/Urea/Zinc Pyrithione, please talk with your doctor, pharmacist, or other health care provider. Selenium/Urea/Zinc Pyrithione is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Selenium/Urea/Zinc Pyrithione. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Selenium/Urea/Zinc Pyrithione resources Selenium/Urea/Zinc Pyrithione Side Effects (in more detail) Selenium/Urea/Zinc Pyrithione Use in Pregnancy & Breastfeeding Selenium/Urea/Zinc Pyrithione Support Group 3 Reviews for Selenium/Urea/Zinc Pyrithione - Add your own review/rating Compare Selenium/Urea/Zinc Pyrithione with other medications Seborrheic Dermatitis Tinea VersicolorSelsun Blue 2 in 1
Generic Name: selenium sulfide topical (se LEE nee um SUL fide TOP ik al)
Brand Names: Dandrex, Head & Shoulders Intensive Treatment, Selenos, Selseb, Selsun Blue, Selsun Blue 2 in 1, Selsun Blue Balanced Treatment, Selsun Blue Moisturizing Treatment, Tersi Foam
Selenium sulfide is an antifungal medication. It prevents fungus from growing on your skin.
Selenium sulfide topical (for the skin) is used to treat dandruff, seborrhea, and tinea versicolor (a fungus that discolors the skin).
Selenium sulfide topical may also be used for other purposes not listed in this medication guide.
What is the most important information I should know about Selsun Blue 2 in 1 (selenium sulfide topical)? Avoid getting this medication in your eyes, nose, or mouth. If it does get into any of these areas, rinse with water. Do not use selenium sulfide topical on sunburned, windburned, dry, chapped, or broken skin.Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.
Do not cover treated skin with a bandage or other dressing unless your doctor has told you to. A light cotton-gauze bandage may be used to protect clothing. Wear loose-fitting clothing made of cotton and other natural fibers until your infection is healed.
Stop using selenium sulfide and call your doctor if you have unusual or severe blistering, itching, redness, peeling, dryness, or irritation of the skin. What should I discuss with my healthcare provider before using Selsun Blue 2 in 1 (selenium sulfide topical)? You should not use this medication if you are allergic to selenium sulfide. FDA pregnancy category C. It is not known whether selenium sulfide is harmful to an unborn baby. Before using selenium sulfide topical, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether selenium sulfide passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I use Selsun Blue 2 in 1 (selenium sulfide topical)?Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.
Shake the selenium sulfide foam well just before each use. Wash your hands after applying this medication.Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.
Do not cover treated skin with a bandage or other dressing unless your doctor has told you to. A light cotton-gauze bandage may be used to protect clothing.
Store this medication at room temperature away from moisture and heat. Keep the medicine canister away from open flame, and do not puncture the can. What happens if I miss a dose?Apply the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not apply extra medicine to make up the missed dose.
What happens if I overdose? Seek emergency medical attention if you think you have used too much of this medicine.An overdose of selenium sulfide topical is not likely to produce life-threatening side effects.
What should I avoid while using Selsun Blue 2 in 1 (selenium sulfide topical)? Avoid getting this medication in your eyes, nose, mouth, rectum, or vagina. If it does get into any of these areas, rinse with water. Do not use selenium sulfide topical on sunburned, windburned, dry, chapped, or broken skin.Avoid covering treated skin areas with tight-fitting, synthetic clothing that doesn't allow air circulation. Wear loose-fitting clothing made of cotton and other natural fibers until your infection is healed.
Selsun Blue 2 in 1 (selenium sulfide topical) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using selenium sulfide and call your doctor if you have unusual or severe blistering, itching, redness, peeling, dryness, or irritation of the skin.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect Selsun Blue 2 in 1 (selenium sulfide topical)?Avoid using other topical medications at the same time you apply selenium sulfide topical, unless your doctor approves. Other skin medications may affect the absorption or effectiveness of selenium sulfide topical.
More Selsun Blue 2 in 1 resources Selsun Blue 2 in 1 Side Effects (in more detail) Selsun Blue 2 in 1 Use in Pregnancy & Breastfeeding Selsun Blue 2 in 1 Support Group 0 Reviews for Selsun Blue 2 in - Add your own review/rating Dandrex Topical Advanced Consumer (Micromedex) - Includes Dosage Information Dandrex Lotion MedFacts Consumer Leaflet (Wolters Kluwer) Selseb MedFacts Consumer Leaflet (Wolters Kluwer) Tersi Foam Prescribing Information (FDA) Tersi Foam MedFacts Consumer Leaflet (Wolters Kluwer) Compare Selsun Blue 2 in 1 with other medications Seborrheic Dermatitis Tinea Versicolor Where can I get more information? Your pharmacist can provide more information about selenium sulfide topical.See also: Selsun Blue 2 in side effects (in more detail)
Selsun Blue Moisturizing Treatment
Generic Name: selenium sulfide topical (se LEE nee um SUL fide TOP ik al)
Brand Names: Dandrex, Head & Shoulders Intensive Treatment, Selenos, Selseb, Selsun Blue, Selsun Blue 2 in 1, Selsun Blue Balanced Treatment, Selsun Blue Moisturizing Treatment, Tersi Foam
Selenium sulfide is an antifungal medication. It prevents fungus from growing on your skin.
Selenium sulfide topical (for the skin) is used to treat dandruff, seborrhea, and tinea versicolor (a fungus that discolors the skin).
Selenium sulfide topical may also be used for other purposes not listed in this medication guide.
What is the most important information I should know about Selsun Blue Moisturizing Treatment (selenium sulfide topical)? Avoid getting this medication in your eyes, nose, or mouth. If it does get into any of these areas, rinse with water. Do not use selenium sulfide topical on sunburned, windburned, dry, chapped, or broken skin.Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.
Do not cover treated skin with a bandage or other dressing unless your doctor has told you to. A light cotton-gauze bandage may be used to protect clothing. Wear loose-fitting clothing made of cotton and other natural fibers until your infection is healed.
Stop using selenium sulfide and call your doctor if you have unusual or severe blistering, itching, redness, peeling, dryness, or irritation of the skin. What should I discuss with my healthcare provider before using Selsun Blue Moisturizing Treatment (selenium sulfide topical)? You should not use this medication if you are allergic to selenium sulfide. FDA pregnancy category C. It is not known whether selenium sulfide is harmful to an unborn baby. Before using selenium sulfide topical, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether selenium sulfide passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. How should I use Selsun Blue Moisturizing Treatment (selenium sulfide topical)?Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.
Shake the selenium sulfide foam well just before each use. Wash your hands after applying this medication.Use this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.
Do not cover treated skin with a bandage or other dressing unless your doctor has told you to. A light cotton-gauze bandage may be used to protect clothing.
Store this medication at room temperature away from moisture and heat. Keep the medicine canister away from open flame, and do not puncture the can. What happens if I miss a dose?Apply the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not apply extra medicine to make up the missed dose.
What happens if I overdose? Seek emergency medical attention if you think you have used too much of this medicine.An overdose of selenium sulfide topical is not likely to produce life-threatening side effects.
What should I avoid while using Selsun Blue Moisturizing Treatment (selenium sulfide topical)? Avoid getting this medication in your eyes, nose, mouth, rectum, or vagina. If it does get into any of these areas, rinse with water. Do not use selenium sulfide topical on sunburned, windburned, dry, chapped, or broken skin.Avoid covering treated skin areas with tight-fitting, synthetic clothing that doesn't allow air circulation. Wear loose-fitting clothing made of cotton and other natural fibers until your infection is healed.
Selsun Blue Moisturizing Treatment (selenium sulfide topical) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using selenium sulfide and call your doctor if you have unusual or severe blistering, itching, redness, peeling, dryness, or irritation of the skin.This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect Selsun Blue Moisturizing Treatment (selenium sulfide topical)?Avoid using other topical medications at the same time you apply selenium sulfide topical, unless your doctor approves. Other skin medications may affect the absorption or effectiveness of selenium sulfide topical.
More Selsun Blue Moisturizing Treatment resources Selsun Blue Moisturizing Treatment Side Effects (in more detail) Selsun Blue Moisturizing Treatment Use in Pregnancy & Breastfeeding Selsun Blue Moisturizing Treatment Support Group 0 Reviews for Selsun Blue Moisturizing Treatment - Add your own review/rating Dandrex Topical Advanced Consumer (Micromedex) - Includes Dosage Information Dandrex Lotion MedFacts Consumer Leaflet (Wolters Kluwer) Selseb MedFacts Consumer Leaflet (Wolters Kluwer) Tersi Foam Prescribing Information (FDA) Tersi Foam MedFacts Consumer Leaflet (Wolters Kluwer) Compare Selsun Blue Moisturizing Treatment with other medications Seborrheic Dermatitis Tinea Versicolor Where can I get more information? Your pharmacist can provide more information about selenium sulfide topical.See also: Selsun Blue Moisturizing Treatment side effects (in more detail)
Tersi Foam
Pronunciation: se-LEE-nee-um
Generic Name: Selenium
Brand Name: Tersi Foam
Tersi Foam is used for:
Treating scalp and skin conditions such as seborrhea or tinea versicolor (a fungal infection). It may also be used for other conditions as determined by your doctor.
Tersi Foam is a antiseborrheic and antifungal combination. It decreases skin cell growth associated with flaking and itching. It also kills sensitive fungi.
Do NOT use Tersi Foam if: you are allergic to any ingredient in Tersi FoamContact your doctor or health care provider right away if any of these apply to you.
Before using Tersi Foam:Some medical conditions may interact with Tersi Foam. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have broken, irritated, inflamed, or oozing skin at the application siteSome MEDICINES MAY INTERACT with Tersi Foam. Because little, if any, of Tersi Foam is absorbed into the blood, the risk of it interacting with another medicine is low.
Ask your health care provider if Tersi Foam may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Tersi Foam:Use Tersi Foam as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Remove jewelry before using Tersi Foam. Shake well before each use. Turn the container upside down to dispense medicine. Apply enough medicine to cover the affected area as directed by your doctor. Rub the medicine in until it is completely absorbed. Wash your hands immediately after using Tersi Foam. If you miss a dose of Tersi Foam, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Tersi Foam.
Important safety information: Tersi Foam is for external use only. Do not get Tersi Foam in your eyes, nose, mouth, or in the genital area. If you get it in any of these areas, rinse right away with cool water. If your symptoms do not get better or if they get worse, check with your doctor. Do not use more often or for longer than prescribed without checking with your doctor. If you use topical products too often, some conditions may become worse. Do not use Tersi Foam for another skin condition at a later time. Do not use Tersi Foam on broken, blistered, or inflamed skin. Tersi Foam may cause harm if it is swallowed. If you may have taken it by mouth, contact your poison control center or emergency room right away. Tersi Foam should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Tersi Foam while you are pregnant. It is not known if Tersi Foam is found in breast milk after topical use. If you are or will be breast-feeding while you use Tersi Foam, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Tersi Foam:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Temporary mild stinging, burning, itching, or irritation of the skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); severe redness, stinging, burning, or irritation.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Tersi side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Tersi Foam may be harmful if swallowed.
Proper storage of Tersi Foam:Store Tersi Foam at room temperature, between 59 and 77 degrees F (15 and 25 degrees C). Store away from heat and direct sunlight. Do not puncture, break, or burn the canister even if it appears to be empty. Keep Tersi Foam out of the reach of children and away from pets.
General information: If you have any questions about Tersi Foam, please talk with your doctor, pharmacist, or other health care provider. Tersi Foam is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Tersi Foam. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Tersi resources Tersi Side Effects (in more detail) Tersi Use in Pregnancy & Breastfeeding Tersi Support Group 0 Reviews for Tersi - Add your own review/rating Tersi Foam Concise Consumer Information (Cerner Multum) Tersi Foam Topical Advanced Consumer (Micromedex) - Includes Dosage Information Tersi Foam Prescribing Information (FDA) Selsun Concise Consumer Information (Cerner Multum) Compare Tersi with other medications Seborrheic Dermatitis Tinea VersicolorSumadan Wash
Pronunciation: SUL-fa-SEET-a-mide/SUL-fur
Generic Name: Sulfacetamide/Sulfur
Brand Name: Examples include Sumadan and Sumaxin
Sumadan Wash is used for:
Treating acne, rosacea, and seborrhea. It may also be used for other conditions as determined by your doctor.
Sumadan Wash is a sulfonamide antibiotic and keratolytic. It works by killing bacteria and shedding the top layer of skin to help treat acne.
Do NOT use Sumadan Wash if: you are allergic to any ingredient in Sumadan Wash you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide you have kidney diseaseContact your doctor or health care provider right away if any of these apply to you.
Before using Sumadan Wash:Some medical conditions may interact with Sumadan Wash. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have eczema or a history of lupusSome MEDICINES MAY INTERACT with Sumadan Wash. Because little, if any, of Sumadan Wash is absorbed into the blood, the risk of it interacting with another medicine is low.
Ask your health care provider if Sumadan Wash may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Sumadan Wash:Use Sumadan Wash as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Wash your hands before and after using Sumadan Wash. Wet the affected area. Apply a generous amount of Sumadan Wash. Massage gently into the skin for 10 to 20 seconds, working into a full lather. Rinse well, then pat dry. Continue to use Sumadan Wash even if your condition improves. Do not miss any doses. If you miss a dose of Sumadan Wash, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Sumadan Wash.
Important safety information: It may take several days for Sumadan Wash to work fully. Avoid getting Sumadan Wash in your eyes, nose, or mouth. If you get Sumadan Wash in any of these areas, rinse immediately with cool tap water. Talk with your doctor before you use any other medicines or cleansers on your skin. Do not apply Sumadan Wash to open wounds or to damaged or burned skin without first checking with your doctor. If you use topical products too often, your condition may become worse. Sumadan Wash should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Sumadan Wash while you are pregnant. It is not known if Sumadan Wash is found in breast milk after topical use. If you are or will be breast-feeding while you use Sumadan Wash, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Sumadan Wash:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Mild irritation, stinging, redness, dryness, or burning of the skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); cracked or extremely dry skin; fever; joint pain; red, swollen, scaling, or blistered skin; severe diarrhea; severe or persistent skin irritation; sores in the mouth; unusual bruising or spots on the skin; unusual tiredness or weakness; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Sumadan side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.
Proper storage of Sumadan Wash:Store Sumadan Wash at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not freeze. Keep Sumadan Wash out of the reach of children and away from pets.
General information: If you have any questions about Sumadan Wash, please talk with your doctor, pharmacist, or other health care provider. Sumadan Wash is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Sumadan Wash. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Sumadan resources Sumadan Side Effects (in more detail) Sumadan Use in Pregnancy & Breastfeeding Sumadan Drug Interactions Sumadan Support Group 0 Reviews for Sumadan - Add your own review/rating Sumadan Wash Prescribing Information (FDA) Avar Cleanser Concise Consumer Information (Cerner Multum) Clarifoam EF Prescribing Information (FDA) Plexion Prescribing Information (FDA) Prascion Cleanser Prescribing Information (FDA) Rosaderm Cleanser Prescribing Information (FDA) Rosanil Cleanser Prescribing Information (FDA) Rosula Prescribing Information (FDA) Sumaxin Wash Prescribing Information (FDA) Zencia Wash Prescribing Information (FDA) Compare Sumadan with other medications Acne Rosacea Seborrheic DermatitisSumaxin TS Emulsion
Pronunciation: sul-fa-SEE-ta-mide/SULL-fer
Generic Name: Sulfacetamide/Sulfur
Brand Name: Examples include Plexion TS and Sumaxin TS
Sumaxin TS Emulsion is used for:
Treating acne, rosacea, and seborrhea. It may also be used for other conditions as determined by your doctor.
Sumaxin TS Emulsion is a sulfonamide antibiotic and keratolytic. It works by killing bacteria and shedding the top layer of skin to help treat acne.
Do NOT use Sumaxin TS Emulsion if: you are allergic to any ingredient in Sumaxin TS Emulsion you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide you have kidney diseaseContact your doctor or health care provider right away if any of these apply to you.
Before using Sumaxin TS Emulsion:Some medical conditions may interact with Sumaxin TS Emulsion. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have eczema or a history of lupusSome MEDICINES MAY INTERACT with Sumaxin TS Emulsion. Tell your health care provider if you are taking any other medicines, especially any of the following:
Silver-containing products (eg, silver sulfadiazine) because they may decrease Sumaxin TS Emulsion's effectiveness Methenamine because it may increase the risk of Sumaxin TS Emulsion's side effectsThis may not be a complete list of all interactions that may occur. Ask your health care provider if Sumaxin TS Emulsion may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Sumaxin TS Emulsion:Use Sumaxin TS Emulsion as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Sumaxin TS Emulsion is for use on the skin only. Sumaxin TS Emulsion may stain clothing and the skin if too much is used. Wash hands before and after using Sumaxin TS Emulsion. Gently wash and dry the affected area. Apply a small amount of Sumaxin TS Emulsion to the affected area. Rub in gently. To clear up your infection completely, continue using Sumaxin TS Emulsion for the full course of treatment even if you feel better in a few days. Sumaxin TS Emulsion works best if it is used at the same time each day. Continue to use Sumaxin TS Emulsion even if you feel well. Do not miss any doses. If you miss a dose of Sumaxin TS Emulsion, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Sumaxin TS Emulsion.
Important safety information: Avoid getting Sumaxin TS Emulsion in your eyes, nose, or mouth. If you get Sumaxin TS Emulsion in your eyes, rinse immediately with cool tap water. Talk with your doctor before you use any other medicines or cleansers on your skin. Do not apply Sumaxin TS Emulsion to open wounds or to damaged or burned skin without first checking with your doctor. If you use topical products too often, your condition may become worse. Sumaxin TS Emulsion only works against bacteria; it does not treat viral infections. Be sure to use Sumaxin TS Emulsion for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future. Long-term or repeated use of Sumaxin TS Emulsion may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this. Sumaxin TS Emulsion should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Sumaxin TS Emulsion while you are pregnant. It is not known if Sumaxin TS Emulsion is found in breast milk after topical use. If you are or will be breast-feeding while you use Sumaxin TS Emulsion, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Sumaxin TS Emulsion:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Mild irritation, stinging, or burning of the skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); cracked or extremely dry skin; fever; joint pain; red, swollen, scaling, or blistered skin; severe diarrhea; sores in the mouth; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Sumaxin TS side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Sumaxin TS Emulsion may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.
Proper storage of Sumaxin TS Emulsion:Store Sumaxin TS Emulsion at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Do not freeze. Keep Sumaxin TS Emulsion out of the reach of children and away from pets.
General information: If you have any questions about Sumaxin TS Emulsion, please talk with your doctor, pharmacist, or other health care provider. Sumaxin TS Emulsion is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Sumaxin TS Emulsion. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Sumaxin TS resources Sumaxin TS Side Effects (in more detail) Sumaxin TS Use in Pregnancy & Breastfeeding Sumaxin TS Drug Interactions 0 Reviews for Sumaxin TS - Add your own review/rating Compare Sumaxin TS with other medications Acne Rosacea Seborrheic DermatitisZetacet Emulsion
Pronunciation: sul-fa-SEE-ta-mide/SULL-fer
Generic Name: Sulfacetamide/Sulfur
Brand Name: Examples include Plexion TS and Sumaxin TS
Zetacet Emulsion is used for:
Treating acne, rosacea, and seborrhea. It may also be used for other conditions as determined by your doctor.
Zetacet Emulsion is a sulfonamide antibiotic and keratolytic. It works by killing bacteria and shedding the top layer of skin to help treat acne.
Do NOT use Zetacet Emulsion if: you are allergic to any ingredient in Zetacet Emulsion you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide you have kidney diseaseContact your doctor or health care provider right away if any of these apply to you.
Before using Zetacet Emulsion:Some medical conditions may interact with Zetacet Emulsion. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have eczema or a history of lupusSome MEDICINES MAY INTERACT with Zetacet Emulsion. Tell your health care provider if you are taking any other medicines, especially any of the following:
Silver-containing products (eg, silver sulfadiazine) because they may decrease Zetacet Emulsion's effectiveness Methenamine because it may increase the risk of Zetacet Emulsion's side effectsThis may not be a complete list of all interactions that may occur. Ask your health care provider if Zetacet Emulsion may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Zetacet Emulsion:Use Zetacet Emulsion as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Zetacet Emulsion is for use on the skin only. Zetacet Emulsion may stain clothing and the skin if too much is used. Wash hands before and after using Zetacet Emulsion. Gently wash and dry the affected area. Apply a small amount of Zetacet Emulsion to the affected area. Rub in gently. To clear up your infection completely, continue using Zetacet Emulsion for the full course of treatment even if you feel better in a few days. Zetacet Emulsion works best if it is used at the same time each day. Continue to use Zetacet Emulsion even if you feel well. Do not miss any doses. If you miss a dose of Zetacet Emulsion, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Zetacet Emulsion.
Important safety information: Avoid getting Zetacet Emulsion in your eyes, nose, or mouth. If you get Zetacet Emulsion in your eyes, rinse immediately with cool tap water. Talk with your doctor before you use any other medicines or cleansers on your skin. Do not apply Zetacet Emulsion to open wounds or to damaged or burned skin without first checking with your doctor. If you use topical products too often, your condition may become worse. Zetacet Emulsion only works against bacteria; it does not treat viral infections. Be sure to use Zetacet Emulsion for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future. Long-term or repeated use of Zetacet Emulsion may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this. Zetacet Emulsion should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Zetacet Emulsion while you are pregnant. It is not known if Zetacet Emulsion is found in breast milk after topical use. If you are or will be breast-feeding while you use Zetacet Emulsion, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Zetacet Emulsion:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Mild irritation, stinging, or burning of the skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); cracked or extremely dry skin; fever; joint pain; red, swollen, scaling, or blistered skin; severe diarrhea; sores in the mouth; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Zetacet side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Zetacet Emulsion may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.
Proper storage of Zetacet Emulsion:Store Zetacet Emulsion at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Do not freeze. Keep Zetacet Emulsion out of the reach of children and away from pets.
General information: If you have any questions about Zetacet Emulsion, please talk with your doctor, pharmacist, or other health care provider. Zetacet Emulsion is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Zetacet Emulsion. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Zetacet resources Zetacet Side Effects (in more detail) Zetacet Use in Pregnancy & Breastfeeding Zetacet Drug Interactions Zetacet Support Group 0 Reviews for Zetacet - Add your own review/rating Compare Zetacet with other medications Acne Rosacea Seborrheic DermatitisAvar LS Cleanser
Pronunciation: SUL-fa-SEET-a-mide SOE-dee-um/SUL-fur
Generic Name: Sulfacetamide Sodium/Sulfur
Brand Name: Avar LS Cleanser
Avar LS Cleanser is used for:
Treating acne, rosacea, and oily, flaky skin (seborrhea). It may also be used for other conditions as determined by your doctor.
Avar LS Cleanser is a sulfonamide antibiotic and keratolytic combination. The sulfonamide works by killing bacteria and the keratolytic works by shedding the top layer of skin.
Do NOT use Avar LS Cleanser if: you are allergic to any ingredient in Avar LS Cleanser you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide you have kidney diseaseContact your doctor or health care provider right away if any of these apply to you.
Before using Avar LS Cleanser:Some medical conditions may interact with Avar LS Cleanser. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have eczema or a history of lupusSome MEDICINES MAY INTERACT with Avar LS Cleanser. Because little, if any, of Avar LS Cleanser is absorbed into the blood, the risk of it interacting with another medicine is low.
Ask your health care provider if Avar LS Cleanser may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Avar LS Cleanser:Use Avar LS Cleanser as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Avar LS Cleanser is for use on the skin only. Avar LS Cleanser may stain clothing and the skin if too much is used. Wash your hands before and immediately after using Avar LS Cleanser. Wet the skin and apply a generous amount of medicine to the affected area. Massage gently into the skin for 10 to 20 seconds, working into a full lather. Rinse well and pat dry. If the affected area becomes excessively dry, check with your doctor. You may need to rinse the medicine off the skin sooner or use it less often. Avar LS Cleanser works best if it is used at the same time(s) each day. Continue to use Avar LS Cleanser even if your condition improves. Do not miss any doses. If you miss a dose of Avar LS Cleanser, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Avar LS Cleanser.
Important safety information: Avar LS Cleanser is for external use only. Do not get it in your eyes, nose, or mouth. If you get it in any of these areas, rinse right away with cool tap water. Talk with your doctor before you use any other medicines or cleansers on your skin. Do not apply Avar LS Cleanser to open wounds or to damaged or burned skin without first checking with your doctor. If you use topical products too often, your condition may become worse. Avar LS Cleanser should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Avar LS Cleanser while you are pregnant. It is not known if Avar LS Cleanser is found in breast milk after topical use. If you are or will be breast-feeding while you use Avar LS Cleanser, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Avar LS Cleanser:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Mild dryness, redness, scaling, stinging, or burning of the skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); butterfly-shaped rash on the face; cracked or extremely dry skin; fever, chills, or sore throat; joint pain; red, swollen, blistered, or peeling skin; seizures; severe skin redness or scaling; skin inflammation or irritation; unusual tiredness or weakness; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Avar LS side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Avar LS Cleanser may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.
Proper storage of Avar LS Cleanser:Store Avar LS Cleanser at room temperature, between 59 and 77 degrees F (15 and 25 degrees C). Keep the container tightly closed. Store away from heat and light. Do not freeze. Keep Avar LS Cleanser out of the reach of children and away from pets.
General information: If you have any questions about Avar LS Cleanser, please talk with your doctor, pharmacist, or other health care provider. Avar LS Cleanser is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Avar LS Cleanser. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Avar LS resources Avar LS Side Effects (in more detail) Avar LS Use in Pregnancy & Breastfeeding Avar LS Drug Interactions 0 Reviews for Avar LS - Add your own review/rating Avar LS Cleanser Concise Consumer Information (Cerner Multum) Clarifoam EF Prescribing Information (FDA) Plexion Prescribing Information (FDA) Prascion Cleanser Prescribing Information (FDA) Rosaderm Cleanser Prescribing Information (FDA) Rosanil Cleanser Prescribing Information (FDA) Rosula Prescribing Information (FDA) Sumadan Wash Prescribing Information (FDA) Sumaxin Wash Prescribing Information (FDA) Zencia Wash Prescribing Information (FDA) Compare Avar LS with other medications Acne Rosacea Seborrheic DermatitisSulfacetamide/Sulfur Emulsion
Pronunciation: sul-fa-SEE-ta-mide/SULL-fer
Generic Name: Sulfacetamide/Sulfur
Brand Name: Examples include Plexion TS and Sumaxin TS
Sulfacetamide/Sulfur Emulsion is used for:
Treating acne, rosacea, and seborrhea. It may also be used for other conditions as determined by your doctor.
Sulfacetamide/Sulfur Emulsion is a sulfonamide antibiotic and keratolytic. It works by killing bacteria and shedding the top layer of skin to help treat acne.
Do NOT use Sulfacetamide/Sulfur Emulsion if: you are allergic to any ingredient in Sulfacetamide/Sulfur Emulsion you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide you have kidney diseaseContact your doctor or health care provider right away if any of these apply to you.
Before using Sulfacetamide/Sulfur Emulsion:Some medical conditions may interact with Sulfacetamide/Sulfur Emulsion. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have eczema or a history of lupusSome MEDICINES MAY INTERACT with Sulfacetamide/Sulfur Emulsion. Tell your health care provider if you are taking any other medicines, especially any of the following:
Silver-containing products (eg, silver sulfadiazine) because they may decrease Sulfacetamide/Sulfur Emulsion's effectiveness Methenamine because it may increase the risk of Sulfacetamide/Sulfur Emulsion's side effectsThis may not be a complete list of all interactions that may occur. Ask your health care provider if Sulfacetamide/Sulfur Emulsion may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Sulfacetamide/Sulfur Emulsion:Use Sulfacetamide/Sulfur Emulsion as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Sulfacetamide/Sulfur Emulsion is for use on the skin only. Sulfacetamide/Sulfur Emulsion may stain clothing and the skin if too much is used. Wash hands before and after using Sulfacetamide/Sulfur Emulsion. Gently wash and dry the affected area. Apply a small amount of Sulfacetamide/Sulfur Emulsion to the affected area. Rub in gently. To clear up your infection completely, continue using Sulfacetamide/Sulfur Emulsion for the full course of treatment even if you feel better in a few days. Sulfacetamide/Sulfur Emulsion works best if it is used at the same time each day. Continue to use Sulfacetamide/Sulfur Emulsion even if you feel well. Do not miss any doses. If you miss a dose of Sulfacetamide/Sulfur Emulsion, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Sulfacetamide/Sulfur Emulsion.
Important safety information: Avoid getting Sulfacetamide/Sulfur Emulsion in your eyes, nose, or mouth. If you get Sulfacetamide/Sulfur Emulsion in your eyes, rinse immediately with cool tap water. Talk with your doctor before you use any other medicines or cleansers on your skin. Do not apply Sulfacetamide/Sulfur Emulsion to open wounds or to damaged or burned skin without first checking with your doctor. If you use topical products too often, your condition may become worse. Sulfacetamide/Sulfur Emulsion only works against bacteria; it does not treat viral infections. Be sure to use Sulfacetamide/Sulfur Emulsion for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future. Long-term or repeated use of Sulfacetamide/Sulfur Emulsion may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this. Sulfacetamide/Sulfur Emulsion should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed. PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Sulfacetamide/Sulfur Emulsion while you are pregnant. It is not known if Sulfacetamide/Sulfur Emulsion is found in breast milk after topical use. If you are or will be breast-feeding while you use Sulfacetamide/Sulfur Emulsion, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Sulfacetamide/Sulfur Emulsion:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Mild irritation, stinging, or burning of the skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); cracked or extremely dry skin; fever; joint pain; red, swollen, scaling, or blistered skin; severe diarrhea; sores in the mouth; yellowing of the skin or eyes.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Sulfacetamide/Sulfur side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Sulfacetamide/Sulfur Emulsion may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.
Proper storage of Sulfacetamide/Sulfur Emulsion:Store Sulfacetamide/Sulfur Emulsion at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Do not freeze. Keep Sulfacetamide/Sulfur Emulsion out of the reach of children and away from pets.
General information: If you have any questions about Sulfacetamide/Sulfur Emulsion, please talk with your doctor, pharmacist, or other health care provider. Sulfacetamide/Sulfur Emulsion is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Sulfacetamide/Sulfur Emulsion. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Sulfacetamide/Sulfur resources Sulfacetamide/Sulfur Side Effects (in more detail) Sulfacetamide/Sulfur Use in Pregnancy & Breastfeeding Sulfacetamide/Sulfur Drug Interactions Sulfacetamide/Sulfur Support Group 18 Reviews for Sulfacetamide/Sulfur - Add your own review/rating Compare Sulfacetamide/Sulfur with other medications Acne Rosacea Seborrheic DermatitisSeb-Prev Gel
sodium sulfacetamide
Dosage Form: gel
SEB-PREV™ GEL (SODIUM SULFACETAMIDE 10%)
Seb-Prev Gel
(Sodium Sulfacetamide 10%)
Rx Only
FOR DERMATOLOGIC USE ONLY
NOT FOR OPHTHALMIC USE
Seb-Prev Gel DescriptionEach gram of Seb-Prev™ Gel contains 100 mg of Sulfacetamide Sodium USP in a vehicle consisting of edetate disodium, glycerin, methylparaben, propylene glycol, purified water, sodium thiosulfate, and xanthan gum.
Sulfacetamide sodium is C8H9N2NaO3S•H2O with a molecular weight of 254.24. Chemically, it is Acetamide N-[(4-aminophenyl)sulfonyl]-, monosodium salt, monohydrate, with the following structural formula:
Sulfacetamide sodium is an odorless, white, crystalline powder with a bitter taste. It is freely soluble in water, sparingly soluble in alcohol, while practically insoluble in benzene, in chloroform, and in ether.
Seb-Prev Gel - Clinical PharmacologySulfacetamide sodium exerts a bacteriostatic effect against sulfonamide sensitive Gram-positive and Gram-negative microorganisms commonly isolated from secondary cutaneous pyogenic infections. It acts by restricting the synthesis of folic acid required by bacteria for growth, by its competition with para-aminobenzoic acid. There are no clinical data available on the degree and rate of systemic absorption of Seb-Prev™ Gel when applied to the skin or scalp. However, significant absorption of sulfacetamide sodium through the skin has been reported.
The following in vitro data are available but their clinical significance is unknown. Organisms which show susceptibility to sulfacetamide sodium are: Streptococci, Staphylococci, E. coli, Klebsiella pneumoniae, Pseudomonas pyocyanea, Salmonella species, Proteus vulgaris, Nocardia and Actinomyces.
Indications and Usage for Seb-Prev GelSeb-Prev™ Gel is intended for topical application in the following scaling dermatoses: seborrheic dermatitis and seborrhea sicca (dandruff). It also is indicated for the treatment of secondary bacterial infections of the skin due to organisms susceptible to sulfonamides.
ContraindicationsSeb-Prev™ Gel is contraindicated in persons with known or suspected hypersensitivity to sulfonamides or to any of the ingredients of the product.
WarningsSulfonamides are known to cause Stevens-Johnson syndrome in hypersensitive individuals. Stevens-Johnson syndrome also has been reported following the use of sulfacetamide sodium topically. Cases of drug-induced systemic lupus erythematosus from topical sulfacetamide also have been reported. In one of these cases, there was a fatal outcome.
Precautions GeneralNonsusceptible organisms, including fungi, may proliferate with the use of this preparation. Hypersensitivity reactions may recur when a sulfonamide is readministered, irrespective of the route of administration, and cross hypersensitivity between different sulfonamides may occur. If Seb-Prev™ Gel produces signs of hypersensitivity or other untoward reactions, discontinue use of the preparation. Systemic absorption of topical sulfonamides is greater following application to large, infected, abraded, denuded, or severely burned areas. Under these circumstances, potentially any of the adverse effects produced by the systemic administration of these agents could occur and appropriate observations and laboratory determinations should be performed.
Information For PatientsPatients should discontinue Seb-Prev™ Gel if the condition becomes worse, or if a rash develops in the area being treated or elsewhere. Seb-Prev™ Gel also should be discontinued promptly and the physician notified if any arthritis, fever, or sores in the mouth develop. For external use only. Avoid contact with eyes and mucous membranes. Keep this and all medications out of reach of children. In case of accidental ingestion, call a physician or poison control center immediately (see OVERDOSAGE).
Drug InteractionsSeb-Prev™ Gel is incompatible with silver preparations.
Carcinogenesis, Mutagenesis, and Impairment of FertilityLong-term animal studies for carcinogenic potential have not been performed on Seb-Prev™ Gel to date. Studies on reproduction and fertility also have not been performed. One author detected chromosomal nondisjunction in the yeast, Saccharomyces cerevisiae, following application of sulfacetamide sodium. The significance of this finding to the topical use of sulfacetamide sodium in the human is unknown.
Pregnancy Teratogenic effects Pregnancy Category CAnimal reproduction studies have not been conducted with Seb-Prev™ Gel. It also is not known whether Seb-Prev™ Gel can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Seb-Prev™ Gel should be given to a pregnant woman only if clearly needed.
Nursing MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Seb-Prev™ Gel is administered to a nursing woman.
Pediatric UseSafety and effectiveness in children under the age of 12 years have not been established.
Adverse ReactionsReports of irritation and hypersensitivity to sulfacetamide sodium are uncommon. The following adverse reactions, reported after administration of sterile ophthalmic sulfacetamide sodium, are noteworthy: instances of Stevens-Johnson syndrome and instances of local hypersensitivity which progressed to a syndrome resembling systemic lupus erythematosus; in one case a fatal outcome has been reported (see WARNINGS).
OverdosageThe oral LD50 of sulfacetamide in mice is 16.5 g/kg. The LD50 for topical administration of sulfacetamide has not been determined. Oral overdosage may cause nausea and vomiting. Large oral overdosage may cause hematuria, crystalluria, and renal shutdown due to the precipitation of sulfa crystals in the renal tubules and the urinary tract. In the event of overdosage, call a physician or poison control center; emergency treatment should be started immediately.
Treatment: The patient should be induced to vomit, even if emesis has occurred spontaneously. Pharmacologic vomiting by the administration of ipecac syrup is a preferred method. However, vomiting should not be induced in patients with impaired consciousness. The action of ipecac is facilitated by physical activity and by the administration of eight to twelve fluid ounces of water. If emesis does not occur within 15 minutes, the dose of ipecac should be repeated. Precautions against aspiration must be taken, especially in infants and children. Following emesis, any drug remaining in the stomach may be absorbed by activated charcoal administered as a slurry with water. If vomiting is unsuccessful or contraindicated, gastric lavage should
be performed. Isotonic and one-half isotonic saline are the lavage solutions of choice. Saline cathartics, such as milk of magnesia, draw water into the bowel by osmosis and, therefore, may be valuable for their action in rapid dilution of bowel content. After emergency treatment, the patient should continue to be medically monitored.
Observe kidney function for up to 1 week and have the patient ingest copious amounts of fluid during this period. Mannitol infusions may be helpful at the first sign of oliguria. Alkalinization of the urine by ingestion of bicarbonate is very helpful in preventing crystallization of sulfa drug in the kidney.
Seb-Prev Gel Dosage and AdministrationSeborrheic dermatitis including seborrhea sicca: Apply to affected areas twice daily (morning and evening), or as directed by your physician. Avoid contact with eyes or mucous membranes. Repeat application as described for eight to ten days.
As the condition subsides, the interval between applications may be lengthened. Applications once or twice weekly or every other week may prevent recurrence. Should the condition recur after stopping therapy, the application of Seb-Prev™ Gel should be reinitiated as at the beginning of treatment.
Secondary cutaneous bacterial infections: Apply to affected areas twice daily for eight to ten days.
How is Seb-Prev Gel SuppliedSeb-Prev™ Gel is available as follows:
30 g tube (NDC 45802-960-94)
60 g tube (NDC 45802-960-96)
Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Do not freeze.
Occasionally, a slight yellowish discoloration may occur when an excessive amount of the product is used and comes in contact with white fabrics. This discoloration is readily removed by ordinary laundering without bleaches.
MANUFACTURED BY
STIEFEL LABORATORIES, INC.
CORAL GABLES, FL 33134
DISTRIBUTED BY
PERRIGO®
ALLEGAN, MI 49010
Rev. 10/07
81084
: 5P600 RC J1
Principal Display Panel - 30 g CartonSeb-Prev™ Gel
(Sodium Sulfacetamide 10%)
For Dermatologic Use Only. Not for Ophthalmic Use.
Rx Only
Seb-Prev(tm) Gel - 30 g Carton
Principal Display Panel - 30 g TubeSeb-Prev™ Gel
(Sodium Sulfacetamide 10%)
For Dermatologic Use Only. Not for Ophthalmic Use.
Rx Only
Seb-Prev(tm) Gel - 30 g Tube
Principal Display Panel - 60 g CartonSeb-Prev™ Gel
(Sodium Sulfacetamide 10%)
For Dermatologic Use Only. Not for Ophthalmic Use.
Rx Only
Seb-Prev(tm) Gel - 60 g Carton
Principal Display Panel - 60 g TubeSeb-Prev™ Gel
(Sodium Sulfacetamide 10%)
For Dermatologic Use Only. Not for Ophthalmic Use.
Rx Only
Seb-Prev(tm) Gel - 60 g Tube
PERRIGO SEB PREV
sodium sulfacetamide gel Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 45802-960 Route of Administration TOPICAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SULFACETAMIDE SODIUM (SULFACETAMIDE) SULFACETAMIDE SODIUM 100 mg in 1 g Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color YELLOW (clear to pale yellow) Score Shape Size Flavor Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 45802-960-94 1 TUBE In 1 CARTON contains a TUBE 1 30 g In 1 TUBE This package is contained within the CARTON (45802-960-94) 2 45802-960-96 1 TUBE In 1 CARTON contains a TUBE 2 60 g In 1 TUBE This package is contained within the CARTON (45802-960-96)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date Unapproved drug other 08/19/2008
Labeler - Perrigo New York Inc (078846912) Revised: 11/2009Perrigo New York Inc More Seb-Prev Gel resources Seb-Prev Gel Side Effects (in more detail) Seb-Prev Gel Use in Pregnancy & Breastfeeding Seb-Prev Gel Support Group 0 Reviews for Seb-Prev - Add your own review/rating Compare Seb-Prev Gel with other medications Seborrheic Dermatitis Secondary Cutaneous Bacterial Infections
Neutrogena Healthy Scalp Shampoo
Pronunciation: sal-ih-SILL-ik AS-id
Generic Name: Salicylic Acid
Brand Name: Examples include Ionil Plus and Neutrogena Healthy Scalp
Neutrogena Healthy Scalp Shampoo is used for:
Relieving scalp itching, flaking, irritation, redness, and scaling due to psoriasis or seborrhea. It may also be used for other conditions as determined by your doctor.
Neutrogena Healthy Scalp Shampoo is a topical salicylate. It works by causing the skin to swell, soften, and then slough or peel in areas where it is applied.
Do NOT use Neutrogena Healthy Scalp Shampoo if: you are allergic to any ingredient in Neutrogena Healthy Scalp ShampooContact your doctor or health care provider right away if any of these apply to you.
Before using Neutrogena Healthy Scalp Shampoo:Some medical conditions may interact with Neutrogena Healthy Scalp Shampoo. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines, foods, or other substances if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to aspirin or a nonsteroidal anti-inflammatory drug (NSAID) (eg, ibuprofen, naproxen, celecoxib) if you have liver or kidney problems, a skin infection, skin irritation, diabetes, or poor blood circulationSome MEDICINES MAY INTERACT with Neutrogena Healthy Scalp Shampoo. Tell your health care provider if you are taking any other medicines, especially any of the following:
Anticoagulants, (eg, heparin, warfarin), aspirin, methotrexate, or sulfonylureas (eg, glipizide) because the risk of side effects may be increased by Neutrogena Healthy Scalp ShampooThis may not be a complete list of all interactions that may occur. Ask your health care provider if Neutrogena Healthy Scalp Shampoo may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
How to use Neutrogena Healthy Scalp Shampoo:Use Neutrogena Healthy Scalp Shampoo as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Wet hair, apply Neutrogena Healthy Scalp Shampoo to scalp, and massage vigorously. Rinse and repeat. Be sure to wash your hands after each use. If you miss a dose of Neutrogena Healthy Scalp Shampoo, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.Ask your health care provider any questions you may have about how to use Neutrogena Healthy Scalp Shampoo.
Important safety information: Neutrogena Healthy Scalp Shampoo is for external use only. Avoid getting Neutrogena Healthy Scalp Shampoo in your eyes, nose, or mouth, or on the genitals. If contact with your eyes occurs, flush with water for 15 minutes. Do not inhale the vapors of Neutrogena Healthy Scalp Shampoo. Overuse of topical products may worsen your condition. Do not use Neutrogena Healthy Scalp Shampoo longer or more often than recommended by your doctor or on the package label. Check with your doctor before use if you have a condition that covers a large area of the body. Be sure to apply Neutrogena Healthy Scalp Shampoo only to the affected area and not to normal healthy skin. Do not use Neutrogena Healthy Scalp Shampoo on skin that is irritated, infected, or reddened. Do not use Neutrogena Healthy Scalp Shampoo on open skin wounds, moles, birthmarks, genital warts, warts on the face, or warts growing hair. Do not use any other medicines or drying products on your skin unless your doctor instructs you otherwise. Neutrogena Healthy Scalp Shampoo may interfere with certain lab test results. Make sure your doctor and lab personnel know you are using Neutrogena Healthy Scalp Shampoo. Neutrogena Healthy Scalp Shampoo is extremely flammable. Do not store or use Neutrogena Healthy Scalp Shampoo near a fire or other open flame. Neutrogena Healthy Scalp Shampoo may be harmful if swallowed. If you may have taken Neutrogena Healthy Scalp Shampoo by mouth, contact your local poison control center or emergency room immediately. Neutrogena Healthy Scalp Shampoo contains a salicylate, which has been linked to Reye syndrome. Do not use Neutrogena Healthy Scalp Shampoo on children or teenagers during or after chickenpox, flu, or other viral infections without checking with your doctor or pharmacist. Use of Neutrogena Healthy Scalp Shampoo is not recommended in CHILDREN younger than 2 years of age without a doctor's instructions. Caution is advised when using Neutrogena Healthy Scalp Shampoo in CHILDREN because they may be more sensitive to its effects. PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Neutrogena Healthy Scalp Shampoo during pregnancy. It is unknown if Neutrogena Healthy Scalp Shampoo is excreted in breast milk. Do not breast-feed while you are using Neutrogena Healthy Scalp Shampoo. Possible side effects of Neutrogena Healthy Scalp Shampoo:All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Dry, peeling, red, or scaling skin.
Seek medical attention right away if any of these SEVERE side effects occur:Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); severe irritation.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Neutrogena Healthy Scalp side effects (in more detail)
If OVERDOSE is suspected:Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include agitation; diarrhea; dizziness; loss of appetite; loss of hearing; mental disturbances; nausea; rapid or difficult breathing; ringing in the ears; seizures; sluggishness; vomiting; yellowing of the skin or eyes.
Proper storage of Neutrogena Healthy Scalp Shampoo:Store Neutrogena Healthy Scalp Shampoo at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not freeze. Do not store in the bathroom. Keep Neutrogena Healthy Scalp Shampoo out of the reach of children and away from pets.
General information: If you have any questions about Neutrogena Healthy Scalp Shampoo, please talk with your doctor, pharmacist, or other health care provider. Neutrogena Healthy Scalp Shampoo is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.This information is a summary only. It does not contain all information about Neutrogena Healthy Scalp Shampoo. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Neutrogena Healthy Scalp resources Neutrogena Healthy Scalp Side Effects (in more detail) Neutrogena Healthy Scalp Use in Pregnancy & Breastfeeding Neutrogena Healthy Scalp Drug Interactions Neutrogena Healthy Scalp Support Group 0 Reviews for Neutrogena Healthy Scalp - Add your own review/rating Compare Neutrogena Healthy Scalp with other medications Acne Dermatological DisordersProlixin Oral Concentrate
Generic Name: fluphenazine hydrochloride
Dosage Form: Oral Concentrate
Prolixin Description
Prolixin (fluphenazine hydrochloride) is a trifluoromethyl phenothiazine derivative intended for the management of schizophrenia. Prolixin Oral Concentrate (Fluphenazine Hydrochloride Oral Solution) contains 5 mg fluphenazine hydrochloride per mL. Inactive ingredients: alcohol 14%, glycerin, purified water, and sodium benzoate.
Prolixin - Clinical PharmacologyProlixin has activity at all levels of the central nervous system as well as on multiple organ systems. The mechanism whereby its therapeutic action is exerted is unknown.
Indications and Usage for ProlixinProlixin is indicated in the management of manifestations of psychotic disorders.
Prolixin has not been shown effective in the management of behavioral complications in patients with mental retardation.
ContraindicationsPhenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. The presence of blood dyscrasia or liver damage precludes the use of fluphenazine hydrochloride. Prolixin (fluphenazine hydrochloride) is contraindicated in patients who have shown hypersensitivity to fluphenazine; cross-sensitivity to phenothiazine derivatives may occur.
Warnings Tardive DyskinesiaTardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.
Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long- term course of the syndrome is unknown.
Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatment are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
(For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Tardive Dyskinesia.)
Neuroleptic Malignant Syndrome (NMS)A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
The use of this drug may impair the mental and physical abilities required for driving a car or operating heavy machinery.
Potentiation of the effects of alcohol may occur with the use of this drug.
Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established.
Usage in PregnancyThe safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.
Precautions GeneralBecause of the possibility of cross-sensitivity, fluphenazine hydrochloride should be used cautiously in patients who have developed cholestatic jaundice, dermatoses or other allergic reactions to phenothiazine derivatives.
Psychotic patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, it should be remembered that reduced amounts of anesthetics or central nervous system depressants may be necessary.
The effects of atropine may be potentiated in some patients receiving fluphenazine because of added anticholinergic effects.
Fluphenazine hydrochloride should be used cautiously in patients exposed to extreme heat or phosphorus insecticides; in patients with a history of convulsive disorders, since grand mal convulsions have been known to occur; and in patients with special medical disorders, such as mitral insufficiency or other cardiovascular diseases and pheochromocytoma.
The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesia should be remembered when patients are on prolonged therapy.
Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
Information for PatientsGiven the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.
Abrupt WithdrawalIn general, phenothiazines do not produce psychic dependence; however, gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high dose therapy. Reports suggest that these symptoms can be reduced if concomitant antiparkinsonian agents are continued for several weeks after phenothiazine is withdrawn.
Facilities should be available for periodic checking of hepatic function, renal function and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN (blood urea nitrogen) becomes abnormal, treatment should be discontinued.
As with any phenothiazine, the physician should be alert to the possible development of “silent pneumonias” in patients under treatment with fluphenazine hydrochloride.
Adverse Reactions Central Nervous SystemThe side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants.
Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as Benztropine Mesylate or intravenous Caffeine and Sodium Benzoate injection, and by subsequent reduction in dosage.
Tardive DyskinesiaSee WARNINGS. The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely.
The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drugs should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome.
Other CNS EffectsOccurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS, Neuroleptic Malignant Syndrome); leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS.
Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered.
Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams.
Autonomic Nervous SystemHypertension and fluctuation in blood pressure have been reported with fluphenazine hydrochloride.
Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency such as mitral insufficiency appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Levarterenol Bitartrate Injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure.
Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage.
In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.
Metabolic and EndocrineWeight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.
Allergic ReactionsSkin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind.
HematologicRoutine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.
HepaticLiver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving fluphenazine hydrochloride who have had no clinical evidence of liver damage.
OthersSudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions.
Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesic, antihistamines, barbiturates, alcohol) may occur.
The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use — skin pigmentation, and lenticular and corneal opacities.
Prolixin Dosage and AdministrationDepending on the severity and duration of symptoms, total daily dosage for adult psychotic patients may range initially from 2.5 to 10.0 mg and should be divided and given at six- to eight-hour intervals.
The smallest amount that will produce the desired results must be carefully determined for each individual, since optimal dosage levels of this potent drug vary from patient to patient. In general, the oral dose has been found to be approximately two to three times the parenteral dose of fluphenazine. Treatment is best instituted with a low initial dosage, which may be increased, if necessary, until the desired clinical effects are achieved. Therapeutic effect is often achieved with doses under 20 mg daily. Patients remaining severely disturbed or inadequately controlled may require upward titration of dosage. Daily doses up to 40 mg may be necessary; controlled clinical studies have not been performed to demonstrate safety of prolonged administration of such doses.
When symptoms are controlled, dosage can generally be reduced gradually to daily maintenance doses of 1.0 or 5.0 mg, often given as a single daily dose. Continued treatment is needed to achieve maximum therapeutic benefits; further adjustments in dosage may be necessary during the course of therapy to meet the patient's requirements.
For psychotic patients who have been stabilized on a fixed daily dosage of orally administered Prolixin (fluphenazine hydrochloride) dosage forms, conversion to the long-acting injectable Prolixin Decanoate may be indicated [see package insert for Prolixin Decanoate (Fluphenazine Decanoate Injection) for conversion information].
For geriatric patients, the suggested starting dose is 1.0 to 2.5 mg daily, adjusted according to the response of the patient.
When the Oral Concentrate dosage form is to be used, the desired dose (measured by a calibrated device only) should be added to at least 60 mL (2 fl oz) of a suitable diluent just prior to administration to insure palatability and stability. Suggested diluents include tomato or fruit juice, milk, and uncaffeinated soft drinks. The Oral Concentrate should not be mixed with beverages containing caffeine (coffee, cola), tannics (tea), or pectinates (apple juice) because of potential incompatibility.
Prolixin Injection (Fluphenazine Hydrochloride Injection USP) is useful when psychotic patients are unable or unwilling to take oral therapy.
How is Prolixin Supplied120 mL bottle with a 1 mL safety-cap dropper calibrated at 0.1 mL and in 0.2 mL increments. 5 mg fluphenazine hydrochloride per mL. NDC 0003-0801-10.
Prolixin (Fluphenazine Hydrochloride) is also available as a sterile aqueous solution for intramuscular use, plus tablets and elixir for oral administration. See specific package insert for complete information.
StorageStore at room temperature; avoid freezing. Protect from light. Keep tightly closed.
Bristol-Myers Squibb Company
Princeton, NJ 08540
1017856A1
P5369-01
Prolixin
fluphenazine hydrochloride solution, concentrate Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0003-0801 Route of Administration ORAL DEA Schedule INGREDIENTS Name (Active Moiety) Type Strength fluphenazine hydrochloride (fluphenazine) Active 5 MILLIGRAM In 1 MILLILITER alcohol Inactive glycerin Inactive water Inactive sodium benzoate Inactive Product Characteristics Color Score Shape Size Flavor Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 0003-0801-10 120 mL (MILLILITER) In 1 BOTTLE, DROPPER None
Revised: 01/2006Bristol-Myers Squibb Company More Prolixin resources Prolixin Side Effects (in more detail)Prolixin DosageProlixin Use in Pregnancy & BreastfeedingProlixin Drug InteractionsProlixin Support Group2 Reviews for Prolixin - Add your own review/rating Compare Prolixin with other medications Psychosis
Prolixin
Generic Name: fluphenazine hydrochloride
Dosage Form: Tablets USP and Elixir USP
Prolixin Description
Prolixin is a trifluoromethyl phenothiazine derivative intended for the management of schizophrenia. Fluphenazine hydrochloride is described chemically as 4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl] propyl]-1-piperazineethanol dihydrochloride and its molecular formula is C22H28F3N3OS2HCl. The molecular structure is shown below:
Prolixin Tablets (Fluphenazine Hydrochloride Tablets) contain 5 and 10 mg fluphenazine hydrochloride per tablet. Inactive ingredients: Aluminum Lakes of the following colorants: [D&C Red No. 27 and D&C Red No. 30 for 10 mg only; FD&C Blue No. 1 for 5 mg only; FD&C Blue No.2 for 10 mg only; FD&C Yellow No. 5 (tartrazine) for 5 mg only; FD&C Yellow No. 6 for 10 mg only], croscarmellose sodium; hydroxypropyl methylcellulose, lactose monohydrate; polyethylene glycol; polysorbate 80, povidone, stearic acid, and titanium dioxide.
Prolixin Elixir (Fluphenazine Hydrochloride Elixir) contains 0.5 mg fluphenazine hydrochloride per mL. Inactive ingredients: alcohol [14% v/v], colorant (FD&C Yellow No. 6), flavors, glycerin, polysorbate 40, purified water, sodium benzoate, and sucrose.
Prolixin - Clinical PharmacologyProlixin has activity at all levels of the central nervous system as well as on multiple organ systems. The mechanism whereby its therapeutic action is exerted is unknown.
Indications and Usage for ProlixinProlixin is indicated in the management of manifestations of psychotic disorders.
Prolixin has not been shown effective in the management of behavioral complications in patients with mental retardation.
ContraindicationsPhenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. The presence of blood dyscrasia or liver damage precludes the use of fluphenazine hydrochloride. Prolixin (fluphenazine hydrochloride) is contraindicated in patients who have shown hypersensitivity to fluphenazine; cross-sensitivity to phenothiazine derivatives may occur.
Warnings Tardive DyskinesiaTardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (anti-psychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.
Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long- term course of the syndrome is unknown.
Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
(For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Tardive Dyskinesia.)
Neuroleptic Malignant Syndrome (NMS)A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).
The diagnosis evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
The use of this drug may impair the mental and physical abilities required for driving or operating heavy machinery.
Potentiation of the effects of alcohol may occur with the use of this drug.
Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established.
Usage in PregnancyThe safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.
Precautions GeneralBecause of the possibility of cross-sensitivity, fluphenazine hydrochloride should be used cautiously in patients who have developed cholestatic jaundice, dermatoses or other allergic reactions to phenothiazine derivatives.
Prolixin Tablets (Fluphenazine Hydrochloride Tablets) 5 mg only contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Psychotic patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, it should be remembered that reduced amounts of anesthetics or central nervous system depressants may be necessary.
The effects of atropine may be potentiated in some patients receiving fluphenazine because of added anticholinergic effects.
Fluphenazine hydrochloride should be used cautiously in patients exposed to extreme heat or phosphorus insecticides; in patients with a history of convulsive disorders, since grand mal convulsions have been known to occur; and in patients with special medical disorders, such as mitral insufficiency or other cardiovascular diseases and pheochromocytoma.
The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesia should be remembered when patients are on prolonged therapy.
Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
Information for PatientsGiven the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.
Abrupt WithdrawalIn general, phenothiazines do not produce psychic dependence; however, gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high dose therapy. Reports suggest that these symptoms can be reduced if concomitant antiparkinsonian agents are continued for several weeks after phenothiazine is withdrawn.
Facilities should be available for periodic checking of hepatic function, renal function and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN (blood urea nitrogen) becomes abnormal, treatment should be discontinued.
As with any phenothiazine, the physician should be alert to the possible development of “silent pneumonias” in patients under treatment with fluphenazine hydrochloride.
Adverse Reactions Central Nervous SystemThe side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants.
Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as benztropine mesylate or intravenous caffeine and sodium benzoate injection, and by subsequent reduction in dosage.
Tardive DyskinesiaSee WARNINGS. The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusions of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely.
The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drugs should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome.
Other CNS EffectsOccurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS, Neuroleptic Malignant Syndrome). Leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS.
Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered.
Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams.
Autonomic Nervous SystemHypertension and fluctuation in blood pressure have been reported with fluphenazine hydrochloride.
Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency (such as mitral insufficiency) appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Levarterenol Bitartrate Injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure.
Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage.
In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.
Metabolic and EndocrineWeight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.
Allergic ReactionsSkin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind.
HematologicRoutine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.
HepaticLiver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving fluphenazine hydrochloride who have had no clinical evidence of liver damage.
OthersSudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions.
Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesic, antihistamines, barbiturates, alcohol) may occur.
The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use — skin pigmentation, and lenticular and corneal opacities.
Prolixin Dosage and AdministrationProlixin Elixir should be inspected prior to use. Upon standing a slight wispy precipitate or globular material may develop due to the flavoring oils separating from the solution (potency is not affected). Gentle shaking redisperses the oils and the solution becomes clear. Solutions that do not clarify should not be used.
Depending on the severity and duration of symptoms, total daily dosage for adult psychotic patients may range initially from 2.5 to 10.0 mg and should be divided and given at six- to eight-hour intervals.
The smallest amount that will produce the desired results must be carefully determined for each individual, since optimal dosage levels of this potent drug vary from patient to patient. In general, the oral dose has been found to be approximately two to three times the parenteral dose of fluphenazine. Treatment is best instituted with a low initial dosage, which may be increased, if necessary, until the desired clinical effects are achieved. Therapeutic effect is often achieved with doses under 20 mg daily. Patients remaining severely disturbed or inadequately controlled may require upward titration of dosage. Daily doses up to 40 mg may be necessary; controlled clinical studies have not been performed to demonstrate safety of prolonged administration of such doses.
When symptoms are controlled, dosage can generally be reduced gradually to daily maintenance doses of 1.0 or 5.0 mg, often given as a single daily dose. Continued treatment is needed to achieve maximum therapeutic benefits; further adjustments in dosage may be necessary during the course of therapy to meet the patient’s requirements.
For psychotic patients who have been stabilized on a fixed daily dosage or orally administered Prolixin (fluphenazine hydrochloride) dosage forms, conversion to the long-acting injectable Prolixin Decanoate may be indicated [see package insert for Prolixin Decanoate (Fluphenazine Decanoate Injection) for conversion information].
For geriatric patients, the suggested starting dose is 1.0 to 2.5 mg daily, adjusted according to the response of the patient.
Prolixin® Injection (Fluphenazine Hydrochloride Injection USP) is useful when psychotic patients are unable or unwilling to take oral therapy.
How is Prolixin SuppliedProlixin® Tablets (Fluphenazine Hydrochloride Tablets USP)
5 mg:each film-coated tablet is green, round, biconvex, debossed with PPP over 877
bottles of 100 NDC 0003-0877-50
10 mg:each film-coated tablet is pink, round, biconvex, debossed with PPP over 956
bottles of 100 NDC 0003-0956-50
Prolixin® Elixir (Fluphenazine Hydrochloride Elixir USP)
0.5 mg/mL (2.5 mg per 5 mL teaspoonful)
60 mL bottle with
calibrated dropper NDC 0003-0820-30
473 mL bottle NDC 0003-0820-50
Prolixin (Fluphenazine Hydrochloride) is also available as an oral solution concentrate and a sterile aqueous solution for intramuscular use. See specific package inserts for complete information.
StorageStore tablets and elixir at room temperature. Protect from light. Keep tightly closed.
Tablets: Avoid excessive heat.
Elixir: Avoid freezing.
APOTHECON®
A Bristol-Myers Squibb Company
Princeton, NJ 08540 USA
1017859A1+
Prolixin
fluphenazine hydrochloride tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0003-0877 Route of Administration ORAL DEA Schedule INGREDIENTS Name (Active Moiety) Type Strength fluphenazine hydrochloride (fluphenazine) Active 5 MILLIGRAM In 1 TABLET FD&C Blue No.1 Inactive FD&C Yellow No. 5 (tartrazine) Inactive croscarmellose sodium Inactive hydroxypropyl methylcellulose Inactive lactose monohydrate Inactive polyethylene glycol Inactive polysorbate 80 Inactive povidone Inactive stearic acid Inactive titanium dioxide Inactive Product Characteristics Color GREEN Score no score Shape ROUND Size 8MM Flavor Imprint Code PPP;877 Contains Coating true Symbol false Packaging # NDC Package Description Multilevel Packaging 1 0003-0877-50 100 TABLET In 1 BOTTLE None
Prolixin
fluphenazine hydrochloride tablet, film coated Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0003-0956 Route of Administration ORAL DEA Schedule INGREDIENTS Name (Active Moiety) Type Strength fluphenazine hydrochloride (fluphenazine) Active 10 MILLIGRAM In 1 TABLET D&C Red No. 27 Aluminum Lake Inactive D&C Red No. 30 Aluminum Lake Inactive FD&C Blue No. 2 Aluminum Lake Inactive FD&C Yellow No. 6 Aluminum Lake Inactive croscarmellose sodium Inactive hydroxypropyl methylcellulose Inactive lactose monohydrate Inactive polyethylene glycol Inactive polysorbate 80 Inactive povidone Inactive stearic acid Inactive titanium dioxide Inactive Product Characteristics Color PINK Score no score Shape ROUND Size 10MM Flavor Imprint Code PPP;956 Contains Coating true Symbol false Packaging # NDC Package Description Multilevel Packaging 1 0003-0956-50 100 TABLET In 1 BOTTLE None
Prolixin
fluphenazine hydrochloride elixir Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0003-0820 Route of Administration ORAL DEA Schedule INGREDIENTS Name (Active Moiety) Type Strength fluphenazine hydrochloride (fluphenazine) Active 0.5 MILLIGRAM In 1 MILLILITER alcohol Inactive 0.14 MILLILITER In 1 MILLILITER FD&C Yellow No. 6 Inactive flavors Inactive glycerin Inactive polysorbate 40 Inactive purified water Inactive sodium benzoate Inactive sucrose Inactive Product Characteristics Color Score Shape Size Flavor Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 0003-0820-30 60 mL (MILLILITER) In 1 BOTTLE, DROPPER None 2 0003-0820-50 473 mL (MILLILITER) In 1 BOTTLE None
Revised: 01/2006APOTHECON More Prolixin resources Prolixin Side Effects (in more detail) Prolixin Dosage Prolixin Use in Pregnancy & Breastfeeding Prolixin Drug Interactions Prolixin Support Group 2 Reviews for Prolixin - Add your own review/rating Prolixin Concise Consumer Information (Cerner Multum) Fluphenazine MedFacts Consumer Leaflet (Wolters Kluwer) Fluphenazine Professional Patient Advice (Wolters Kluwer) fluphenazine Concise Consumer Information (Cerner Multum) fluphenazine decanoate Monograph (AHFS DI) Compare Prolixin with other medications Psychosis
Fluphenazine Elixir
Dosage Form: elixir
Fluphenazine Hydrochloride
Elixir USP
Rx ONLY
Increased Mortality in Elderly Patients with Dementia-Related PsychosisElderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Fluphenazine Hydrochloride Elixir USP is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).
Fluphenazine Elixir DescriptionFluphenazine hydrochloride is a trifluoromethyl phenothiazine derivative intended for the management of schizophrenia. Fluphenazine hydrochloride is described chemically as 4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]-1-piperazineethanol dihydrochloride and its molecular formula is C22H26F3N3OS • 2HCl.
The structural formula is shown below:
MW = 510.44
Each mL of fluphenazine hydrochloride elixir for oral administration, contains 0.5 mg fluphenazine hydrochloride and alcohol 14% (v/v). Inactive ingredients: colorant (FD&C Yellow No. 6), flavor, glycerin, purified water, sodium benzoate, and sucrose. The pH range is 5.3 to 5.8.
Fluphenazine Elixir - Clinical PharmacologyFluphenazine hydrochloride has activity at all levels of the central nervous system as well as on multiple organ systems. The mechanism whereby its therapeutic action is exerted is unknown.
Indications and Usage for Fluphenazine ElixirFluphenazine hydrochloride elixir is indicated in the management of manifestations of psychotic disorders.
Fluphenazine hydrochloride has not been shown effective in the management of behavioral complications in patients with mental retardation.
ContraindicationsPhenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. The presence of blood dyscrasia or liver damage precludes the use of fluphenazine hydrochloride. Fluphenazine hydrochloride is contraindicated in patients who have shown hypersensitivity to fluphenazine; cross sensitivity to phenothiazine derivatives may occur.
Warnings Increased Mortality in Elderly Patients with Dementia-Related PsychosisElderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Fluphenazine Hydrochloride Elixir USP is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING).
Tardive DyskinesiaTardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.
Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
(For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Tardive Dyskinesia.)
Neuroleptic Malignant Syndrome (NMS)A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
The use of this drug may impair the mental and physical abilities required for driving or operating heavy machinery.
Potentiation of the effects of alcohol may occur with the use of this drug.
Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established.
Usage In Pregnancy Non-teratogenic EffectsNeonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.
Fluphenazine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.
Precautions GeneralBecause of the possibility of cross-sensitivity, fluphenazine hydrochloride should be used cautiously in patients who have developed cholestatic jaundice, dermatoses or other allergic reactions to phenothiazine derivatives.
Psychotic patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, it should be remembered that reduced amounts of anesthetics or central nervous system depressants may be necessary.
The effects of atropine may be potentiated in some patients receiving fluphenazine because of added anticholinergic effects.
Fluphenazine hydrochloride should be used cautiously in patients exposed to extreme heat or phosphorous insecticides; in patients with a history of convulsive disorders, since grand mal convulsions have been known to occur; and in patients with special medical disorders, such as mitral insufficiency or other cardiovascular diseases and pheochromocytoma.
The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesia should be remembered when patients are on prolonged therapy.
Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
Leukopenia, Neutropenia and AgranulocytosisIn clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents.
Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Fluphenazine Hydrochloride Elixir USP at the first sign of a decline in WBC in the absence of other causative factors.
Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue Fluphenazine Hydrochloride Elixir USP and have their WBC followed until recovery.
Information for PatientsGiven the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.
Abrupt WithdrawalIn general, phenothiazines do not provide psychic dependence; however, gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high dose therapy. Reports suggest that these symptoms can be reduced if concomitant antiparkinsonian agents are continued for several weeks after the phenothiazine is withdrawn.
Facilities should be available for periodic checking of hepatic function, renal function and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN (blood urea nitrogen) becomes abnormal, treatment should be discontinued.
As with any phenothiazine, the physician should be alert to the possible development of "silent pneumonias" in patients under treatment with fluphenazine hydrochloride.
Adverse Reactions Central Nervous SystemThe side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants.
Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as Benztropine Mesylate or Intravenous Caffeine and Sodium Benzoate Injection, and by subsequent reduction in dosage.
Tardive DyskinesiaSee WARNINGS. The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely.
The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome.
Other CNS EffectsOccurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS, Neuroleptic Malignant Syndrome). Leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS.
Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered.
Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams.
Autonomic Nervous SystemHypertension and fluctuation in blood pressure have been reported with fluphenazine hydrochloride.
Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency (such as mitral insufficiency) appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Levarterenol Bitartrate Injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure.
Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage.
In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.
Metabolic and EndocrineWeight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.
Allergic ReactionsSkin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind.
HematologicRoutine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.
HepaticLiver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving fluphenazine hydrochloride who have had no clinical evidence of liver damage.
OthersSudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions.
Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol) may occur.
The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use - skin pigmentation, and lenticular and corneal opacities.
Fluphenazine Elixir Dosage and AdministrationDepending on the severity and duration of symptoms, total daily dosage for adult psychotic patients may range initially from 2.5 to 10.0 mg and should be divided and given at six- to eight-hour intervals.
The smallest amount that will produce the desired results must be carefully determined for each individual, since optimal dosage levels of this potent drug may vary from patient to patient. In general, the oral dose has been found to be approximately two to three times the parenteral dose of fluphenazine. Treatment is best instituted with a low initial dosage, which may be increased, if necessary, until the desired clinical effects are achieved. Therapeutic effect is often achieved with doses under 20 mg daily. Patients remaining severely disturbed or inadequately controlled may require upward titration of dosage. Daily doses up to 40 mg may be necessary; controlled clinical studies have not been performed to demonstrate safety of prolonged administration of such doses.
When symptoms are controlled, dosage can generally be reduced gradually to daily maintenance doses of 1 or 5 mg, often given as a single daily dose. Continued treatment is needed to achieve maximum therapeutic benefits; further adjustments in dosage may be necessary during the course of therapy to meet the patient's requirements.
For psychotic patients who have been stabilized on a fixed daily dosage of orally administered fluphenazine hydrochloride dosage forms, conversion to the long-acting injectable fluphenazine decanoate may be indicated (see package insert for fluphenazine decanoate injection for conversion information).
For geriatric patients, the suggested starting dose is 1 to 2.5 mg daily, adjusted according to the response of the patient.
Fluphenazine hydrochloride injection is useful when psychotic patients are unable or unwilling to take oral therapy.
How is Fluphenazine Elixir SuppliedFluphenazine Hydrochloride Elixir USP 0.5 mg/mL (2.5 mg per 5 mL teaspoonful), available as an orange-colored, raspberry flavored elixir and is supplied in the following sizes:
60 mL bottle with calibrated dropper NDC 0121-0654-02
473 mL bottle NDC 0121-0654-16
StorageStore at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature].
Avoid freezing.
Dispense in tight, light-resistant containers only.
Pharmaceutical Associates, Inc.
Greenville, SC 29605
www.paipharma.com
R08/10
PRINCIPAL DISPLAY PANEL - 60 mL Bottle Label60 mL
NDC 0121-0654-02
Fluphenazine
Hydrochloride
Elixir USP
0.5 mg per mL
(2.5 mg/5 mL)
Rx ONLY
pai
Pharmaceutical
Associates, Inc.
Greenville, SC 29605
R09/05
LOT:
EXP:
FLUPHENAZINE HYDROCHLORIDE
fluphenazine hydrochloride elixir Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0121-0654 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fluphenazine Hydrochloride (Fluphenazine) Fluphenazine Hydrochloride 0.5 mg in 1 mL Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found Product Characteristics Color ORANGE Score Shape Size Flavor RASPBERRY Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 0121-0654-02 60 mL In 1 BOTTLE None 2 0121-0654-16 473 mL In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA040106 08/31/2010
Labeler - Pharmaceutical Associates, Inc. (044940096) Establishment Name Address ID/FEI Operations Pharmaceutical Associates, Inc. 044940096 MANUFACTURE Revised: 09/2010Pharmaceutical Associates, Inc. More Fluphenazine Elixir resources Fluphenazine Elixir Side Effects (in more detail)Fluphenazine Elixir DosageFluphenazine Elixir Use in Pregnancy & BreastfeedingDrug ImagesFluphenazine Elixir Drug InteractionsFluphenazine Elixir Support Group2 Reviews for Fluphenazine - Add your own review/rating Compare Fluphenazine Elixir with other medications Psychosis
Evoclin
clindamycin phosphate
Dosage Form: aerosol, foam
FULL PRESCRIBING INFORMATION
Indications and Usage for Evoclin
Evoclin Foam is indicated for topical application in the treatment of acne vulgaris in patients 12 years and older.
Evoclin Dosage and AdministrationEvoclin Foam is for topical use only, and not for oral, ophthalmic, or intravaginal use.
Apply Evoclin Foam once daily to affected areas after the skin is washed with mild soap and allowed to fully dry. Use enough to cover the entire affected area.
The contents of Evoclin Foam are flammable; avoid fire, flame and/or smoking during and immediately following application.
Dosage Forms and StrengthsWhite to off-white thermolabile foam. Each gram of Evoclin Foam contains, as dispensed, 12 mg (1.2%) of clindamycin phosphate, equivalent to 10 mg (1%) of clindamycin.
ContraindicationsEvoclin Foam is contraindicated in individuals with a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.
Warnings and Precautions ColitisSystemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. If significant diarrhea occurs, Evoclin Foam should be discontinued. [See Adverse Reactions (6.2).]
Severe colitis has occurred following oral or parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.
Studies indicate a toxin(s) produced by Clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.
IrritationEvoclin Foam can cause irritation.
Avoid contact of Evoclin Foam with eyes. If contact occurs, rinse eyes thoroughly with water.
Evoclin Foam should be prescribed with caution in atopic individuals.
Adverse Reactions Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
A total of 439 subjects with mild to moderate acne vulgaris were treated once daily for 12 weeks with Evoclin Foam.
The incidence of adverse reactions occurring in ?1% of the subjects in clinical trials comparing Evoclin Foam, and its vehicle is presented in Table 1.
Table 1: Adverse Reactions Occurring in ?1% of Subjects Adverse Reactions Number (%) of Subjects Evoclin Foam Vehicle Foam N = 439 N = 154 Headache 12 (3%) 1 (1%) Application site burning 27 (6%) 14 (9%) Application site pruritus 5 (1%) 5 (3%) Application site dryness 4 (1%) 5 (3%) Application site reaction, not otherwise specified 3 (1%) 4 (3%)In a contact sensitization study, none of the 203 subjects developed evidence of allergic contact sensitization to Evoclin Foam.
Postmarketing ExperienceThe following adverse reactions have been identified during post approval use of Evoclin Foam: application site pain, application site erythema, diarrhea, urticaria, abdominal pain, hypersensitivity, rash, abdominal discomfort, nausea, seborrhea, application site rash, dizziness, and pain of skin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Abdominal pain and gastrointestinal disturbances, as well as gram-negative folliculitis, have also been reported in association with the use of topical formulations of clindamycin. Orally and parenterally administered clindamycin have been associated with severe colitis, which may end fatally.
Drug Interactions ErythromycinEvoclin Foam should not be used in combination with topical or oral erythromycin-containing products due to possible antagonism to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.
Neuromuscular Blocking AgentsClindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Evoclin Foam should be used with caution in patients receiving such agents.
USE IN SPECIFIC POPULATIONS PregnancyPregnancy Category B: There are no adequate and well-controlled studies in pregnant women treated with Evoclin Foam. Evoclin Foam should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.
Reproduction studies have been performed in rats and mice using subcutaneous and oral doses of clindamycin phosphate, clindamycin hydrochloride and clindamycin palmitate hydrochloride. These studies revealed no evidence of fetal harm. The highest dose used in the rat and mouse teratogenicity studies was equivalent to a clindamycin phosphate dose of 432 mg/kg. For a rat, this dose is 84 fold higher, and for a mouse 42 fold higher, than the anticipated human dose of clindamycin phosphate from Evoclin Foam based on a mg/m2 comparison.
Nursing MothersIt is not known whether clindamycin is excreted in human milk following use of Evoclin Foam. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
If used during lactation and Evoclin Foam is applied to the chest, care should be taken to avoid accidental ingestion by the infant.
Pediatric UseSafety and effectiveness of Evoclin Foam in children under the age of 12 have not been studied.
Geriatric UseThe clinical study with Evoclin Foam did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently than younger subjects.
Evoclin DescriptionEvoclin (clindamycin phosphate) Foam contains clindamycin (1%) as clindamycin phosphate.
Clindamycin phosphate is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic, lincomycin.
The chemical name for clindamycin phosphate is methyl 7 - chloro - 6,7,8 - trideoxy - 6 - (1 - methyl - trans - 4 - propyl - L - 2 - pyrrolidinecarboxamido) - 1 - thio - L - threo - ? - D - galacto - octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:
Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97 g/mol
Evoclin Foam contains clindamycin (1%) as clindamycin phosphate, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.
Evoclin - Clinical Pharmacology Mechanism of ActionMechanism of action in acne vulgaris is unknown. [See Microbiology (12.4)]
PharmacodynamicsPharmacodynamics of Evoclin Foam is unknown.
PharmacokineticsIn an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of Evoclin Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a clindamycin gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for Evoclin Foam than for the clindamycin gel, 1%.
Following multiple applications of Evoclin Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.
MicrobiologyNo microbiology studies were conducted in the clinical trials with this product.
Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with Evoclin Foam. P. acnes resistance to clindamycin has been documented.
Inducible Clindamycin Resistance
The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.
Cross Resistance
Resistance to clindamycin is often associated with resistance to erythromycin.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of FertilityThe carcinogenicity of a 1.2% clindamycin phosphate gel similar to Evoclin Foam was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 3 and 15 times higher than the human dose of clindamycin phosphate from 5 milliliters of Evoclin Foam, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals.
A 1.2% clindamycin phosphate gel similar to Evoclin Foam caused a statistically significant shortening of the median time to tumor onset in a study in hairless mice in which tumors were induced by exposure to simulated sunlight.
Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Reproduction studies in rats using oral doses of clindamycin hydrochloride and clindamycin palmitate hydrochloride have revealed no evidence of impaired fertility.
Clinical StudiesIn one multicenter, randomized, double-blind, vehicle-controlled clinical trial, subjects with mild to moderate acne vulgaris used Evoclin Foam or the vehicle Foam once daily for twelve weeks. Treatment response, defined as the proportion of subjects clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in Table 2.
Table 2: Efficacy Results at Week 12 * P < 0.05 Efficacy ParametersEvoclin Foam
N=386Vehicle Foam
N=127 Treatment response (ISGA) 31% 18%* Percent reduction in lesion counts Inflammatory Lesions 49% 35%* Noninflammatory Lesions 38% 27%* Total Lesions 43% 31%* How Supplied/Storage and Handling How SuppliedEvoclin Foam containing clindamycin phosphate equivalent to 10 mg clindamycin per gram, is white to off-white in color and thermolabile. It is available in the following sizes:
100 gram aerosol can - NDC 0145-0061-00 50 gram aerosol can - NDC 0145-0061-50 Storage and HandlingStore at controlled room temperature between 68° to 77°F (20° to 25°C).
Flammable. Avoid fire, flame or smoking during and immediately following application.
Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperature above 120°F (49°C).
Keep out of reach of children.
Patient Counseling InformationSee FDA-Approved patient labeling (Patient Information).
Instructions for Use Patients should be advised to wash their skin with mild soap and allow it to dry before applying Evoclin Foam. Patients should use enough Evoclin Foam to cover the face and to apply once daily. Patients should dispense Evoclin Foam directly into the cap or onto a cool surface. Patients should wash their hands after applying Evoclin Foam. Skin IrritationEvoclin Foam may cause irritation such as erythema, scaling, itching, burning, or stinging.
ColitisIn the event a patient treated with Evoclin Foam experiences severe diarrhea or gastrointestinal discomfort, Evoclin Foam should be discontinued and a physician should be contacted.
EVC:2PI
Patient Information
Evoclin (Ev-o-clin)
(clindamycin phosphate) Foam
Important: For skin use only. Do not use Evoclin Foam in your eyes, mouth or vagina.Read the Patient Information that comes with Evoclin Foam before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment.
What is Evoclin Foam?
Evoclin Foam is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older.
It is not known if Evoclin Foam is safe and effective in children under 12 years of age.
Who should not use Evoclin Foam?
Do not use Evoclin Foam if you:
have Crohn’s disease have ulcerative colitis have had inflammation of the colon (colitis) or severe diarrhea with past antibiotic useTell your doctor if you are not sure if you have any of the conditions listed above.
What should I tell my doctor before using Evoclin Foam?
Before you use Evoclin Foam, tell your doctor if you:
have a history of eczema are planning to have surgery. Evoclin Foam may affect how certain medicines work that may be given during surgery. have any other medical conditions are pregnant or planning to become pregnant. It is not known if Evoclin Foam may harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if Evoclin Foam passes through your breast milk. You and your doctor should decide if you will use Evoclin Foam or breastfeed. If you use Evoclin Foam while breastfeeding and Evoclin Foam is applied on the chest, take care to avoid getting Evoclin Foam into your baby’s mouth.Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Evoclin Foam may affect the way other medicines work and other medicines may affect how Evoclin Foam works.
Especially tell your doctor if you take erythromycin or use products on your skin that contain erythromycin.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I use Evoclin Foam?
Evoclin Foam is for use on the skin only. Do not get Evoclin Foam in your eyes, mouth or vagina. Use Evoclin Foam exactly as your doctor tells you to use it. See the “Instructions for Applying Evoclin Foam” below. Apply Evoclin Foam 1 time a day. Wash your skin with mild soap and water and dry before applying Evoclin Foam. Do not dispense Evoclin Foam directly onto your hands or face, because the foam will begin to melt on contact with warm skin.Instructions for Applying Evoclin Foam.
Remove the clear cap from the Evoclin Foam can (See Figure A).Figure A: Remove clear cap.
Line up the black circle with the nozzle (See Figure B).Figure B: Line up the black circle with the nozzle.
Hold the can upright and firmly press the nozzle to dispense Evoclin Foam (See Figure C).Figure C: Hold can upright and press nozzle firmly to dispense.
Dispense Evoclin Foam into the clear cap or onto a cool surface (see Figure D).
Figure D: Dispense Evoclin Foam into clear cap.
Dispense enough Evoclin Foam to cover the affected area (see Figure E).Figure E: Dispense enough Evoclin Foam to cover affected area.
If the can seems warm or the foam seems runny, run the can under cold water (See Figure F).Figure F: If the can seems warm or the foam is runny, run the can under cold water.
Pick up small amounts of Evoclin Foam with your fingertips and gently rub the foam into the affected area until the foam disappears (See Figure G).Figure G: Pick up a small amount of Evoclin Foam on your fingertips and gently rub into the affected area until the foam disappears.
Wash your hands after applying Evoclin.Throw away any of the unused medicine that you dispensed out of the can.
What should I avoid while using Evoclin Foam?
Evoclin Foam is flammable. Avoid fire, flames, or smoking during and right after you apply Evoclin Foam to your skin. Avoid getting Evoclin Foam in or near your eyes. If you get Evoclin Foam in your eyes, rinse your eyes well with water.What are possible side effects with Evoclin Foam?
Evoclin Foam can cause serious side effects including:
Inflammation of the colon (colitis). Clindamycin can cause severe colitis that may lead to death. Stop using Evoclin Foam and call your doctor right away if you have severe watery diarrhea, or bloody diarrhea.The most common side effects of Evoclin Foam include:
Skin irritation. Evoclin Foam may cause skin irritation such as burning, itching, or dryness. Headache.Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the side effects of Evoclin Foam. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to Stiefel at 1-888-784-3335 (1-888- STIEFEL).
How should I store Evoclin Foam?
Store Evoclin Foam at room temperature between 68° to 77°F (20° to 25°C). Keep Evoclin Foam away from heat. Never throw the can into a fire, even if the can is empty. Do not store Evoclin Foam at temperatures above 120°F (49°C). Do not break through (puncture) the Evoclin Foam can.Keep Evoclin Foam and all medicines out of the reach of children.
General information about the safe and effective use of Evoclin Foam:
Medicines are sometimes prescribed for purposes other than those listed in Patient Information. Do not use Evoclin Foam for a condition for which it was not prescribed. Do not give Evoclin Foam to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about Evoclin Foam. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about Evoclin Foam that is written for health professionals.
What are the ingredients in Evoclin Foam?
Active ingredient: clindamycin phosphate
Inactive ingredients: cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol. The can is pressurized with a hydrocarbon (propane/butane) propellant.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Manufactured for:
Stiefel Laboratories, Inc.
Research Triangle Park, NC 27709
EVC:2PIL
Evoclin is a registered trademark of Stiefel Laboratories, Inc.
©2010 Stiefel Laboratories, Inc.
December/2010
Principal Display Panel
NDC 0145-0061-50
Evoclin®
(clindamycin phosphate)
Foam, 1%
50 g
Rx only
FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.
Description: Evoclin® (clindamycin phosphate) Foam 1%, contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram in a thermolabile hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol (58%), polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.
Dosage: Use only as prescribed by your physician. See package insert for full prescribing information.
Warning: FLAMMABLE. AVOID FIRE, FLAME, OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION.
Keep out of reach of children. Avoid contact with eyes.
Contents under pressure. Do not puncture or incinerate container. Do not expose to heat or store at temperatures above 120°F (49°C).
Store at controlled room temperature, 68°-77°F (20°-25°C).
CFC FREE
Manufactured for
Stiefel Laboratories, Inc.
Research Triangle Park, NC 27709
For additional information:
1-888-784-3335 (1-888-STIEFEL)
or visit www.Evoclin.com
111674
©2011 Stiefel Laboratories, Inc.
Evoclin is a registered trademark of Stiefel Laboratories, Inc.
Made in China
10000000090860
Evoclin
clindamycin phosphate aerosol, foam Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0145-0061 Route of Administration TOPICAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CLINDAMYCIN PHOSPHATE (CLINDAMYCIN) CLINDAMYCIN PHOSPHATE 10 mg in 1 g Inactive Ingredients Ingredient Name Strength CETYL ALCOHOL ALCOHOL POLYSORBATE 60 POTASSIUM HYDROXIDE PROPYLENE GLYCOL WATER STEARYL ALCOHOL Product Characteristics Color Score Shape Size Flavor Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 0145-0061-00 1 CAN In 1 CARTON contains a CAN 1 100 g In 1 CAN This package is contained within the CARTON (0145-0061-00) 2 0145-0061-61 6 CAN In 1 CARTON contains a CAN (0145-0061-10) 2 0145-0061-10 10 g In 1 CAN This package is contained within the CARTON (0145-0061-61) 3 0145-0061-50 1 CAN In 1 CARTON contains a CAN 3 50 g In 1 CAN This package is contained within the CARTON (0145-0061-50)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA050801 10/05/2009
Labeler - Stiefel Laboratories Inc (808842343) Revised: 07/2011Stiefel Laboratories Inc More Evoclin resources Evoclin Side Effects (in more detail) Evoclin Use in Pregnancy & Breastfeeding Evoclin Drug Interactions Evoclin Support Group 0 Reviews for Evoclin - Add your own review/rating Evoclin Foam MedFacts Consumer Leaflet (Wolters Kluwer) Evoclin Consumer Overview Evoclin Topical Advanced Consumer (Micromedex) - Includes Dosage Information Cleocin T Gel MedFacts Consumer Leaflet (Wolters Kluwer) Cleocin Vaginal Advanced Consumer (Micromedex) - Includes Dosage Information ClindaMax Cream MedFacts Consumer Leaflet (Wolters Kluwer) Clindesse Consumer Overview Clindesse Cream MedFacts Consumer Leaflet (Wolters Kluwer) Compare Evoclin with other medications Acne Perioral Dermatitis
Cetirizine
Dosage Form: oral syrup
Cetirizine HYDROCHLORIDE SYRUP
For Oral Use
6300
Rx only
Cetirizine Description
Cetirizine hydrochloride is an orally active and selective H1-receptor antagonist. The chemical name is (±)-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid, dihydrochloride. Cetirizine hydrochloride is a racemic compound and its structural formula is:
C21H25ClN2O3•2HCl M.W. 461.82
Cetirizine hydrochloride is a white, crystalline powder and is water soluble. Cetirizine hydrochloride syrup is a colorless to slightly yellow syrup containing Cetirizine hydrochloride at a concentration of 1 mg/mL (5 mg/5 mL) for oral administration. The pH is between 4 and 5. The inactive ingredients of the syrup are: artificial banana flavor, glacial acetic acid, glycerin, methylparaben, propylene glycol, propylparaben, purified water, saccharin sodium, sodium acetate, and sucrose.
Cetirizine - Clinical Pharmacology Mechanism of ActionsCetirizine, a human metabolite of hydroxyzine, is an antihistamine; its principal effects are mediated via selective inhibition of peripheral H1 receptors. The antihistaminic activity of Cetirizine has been clearly documented in a variety of animal and human models. In vivo and ex vivo animal models have shown negligible anticholinergic and antiserotonergic activity. In clinical studies, however, dry mouth was more common with Cetirizine than with placebo. In vitro receptor binding studies have shown no measurable affinity for other than H1 receptors. Autoradiographic studies with radiolabeled Cetirizine in the rat have shown negligible penetration into the brain. Ex vivo experiments in the mouse have shown that systemically administered Cetirizine does not significantly occupy cerebral H1 receptors.
Pharmacokinetics AbsorptionCetirizine was rapidly absorbed with a time to maximum concentration (Tmax) of approximately 1 hour following oral administration of tablets or syrup in adults. Comparable bioavailability was found between the tablet and syrup dosage forms. When healthy volunteers were administered multiple doses of Cetirizine (10 mg tablets once daily for 10 days), a mean peak plasma concentration (Cmax) of 311 ng/mL was observed. No accumulation was observed. Cetirizine pharmacokinetics were linear for oral doses ranging from 5 to 60 mg. Food had no effect on the extent of Cetirizine exposure (AUC) but Tmax was delayed by 1.7 hours and Cmax was decreased by 23% in the presence of food.
DistributionThe mean plasma protein binding of Cetirizine is 93%, independent of concentration in the range of 25 to 1000 ng/mL, which includes the therapeutic plasma levels observed.
MetabolismA mass balance study in 6 healthy male volunteers indicated that 70% of the administered radioactivity was recovered in the urine and 10% in the feces. Approximately 50% of the radioactivity was identified in the urine as unchanged drug. Most of the rapid increase in peak plasma radioactivity was associated with parent drug, suggesting a low degree of first-pass metabolism. Cetirizine is metabolized to a limited extent by oxidative O-dealkylation to a metabolite with negligible antihistaminic activity. The enzyme or enzymes responsible for this metabolism have not been identified.
EliminationThe mean elimination half-life in 146 healthy volunteers across multiple pharmacokinetic studies was 8.3 hours and the apparent total body clearance for Cetirizine was approximately 53 mL/min.
Interaction StudiesPharmacokinetic interaction studies with Cetirizine in adults were conducted with pseudoephedrine, antipyrine, ketoconazole, erythromycin and azithromycin. No interactions were observed. In a multiple dose study of theophylline (400 mg once daily for 3 days) and Cetirizine (20 mg once daily for 3 days), a 16% decrease in the clearance of Cetirizine was observed. The disposition of theophylline was not altered by concomitant Cetirizine administration.
Special Populations Pediatric PatientsIn pediatric patients aged 2 to 5 years who received 5 mg of Cetirizine, the mean Cmax was 660 ng/mL. Based on cross study comparisons, the weight normalized, apparent total body clearance was 81 to 111% greater and the elimination half life was 33 to 41% shorter in the pediatric population than in adults. In pediatric patients aged 6 to 23 months who received a single dose of 0.25 mg/kg Cetirizine oral solution (mean dose 2.3 mg), the mean Cmax was 390 ng/mL. Based on cross-study comparisons, the weight-normalized, apparent total body clearance was 304% greater and the elimination half-life was 63% shorter in this pediatric population compared to adults. The average AUC(0-t) in children 6 months to < 2 years of age receiving the maximum dose of Cetirizine solution (2.5 mg twice a day) is expected to be two-fold higher than that observed in adults receiving a dose of 10 mg Cetirizine tablets once a day.
Effect of GenderThe effect of gender on Cetirizine pharmacokinetics has not been adequately studied.
Effect of RaceNo race-related differences in the kinetics of Cetirizine have been observed.
PharmacodynamicsCetirizine hydrochloride at doses of 5 and 10 mg strongly inhibited the wheal and flare caused by intradermal injection of histamine in 19 pediatric volunteers (aged 5 to 12 years) and the activity persisted for at least 24 hours. In a 35 day study in children aged 5 to 12, no tolerance to the antihistaminic (suppression of wheal and flare response) effects of Cetirizine hydrochloride was found. In 10 infants 7 to 25 months of age who received 4 to 9 days of Cetirizine in an oral solution (0.25 mg/kg bid), there was a 90% inhibition of histamine-induced (10 mg/mL) cutaneous wheal and 87% inhibition of the flare 12 hours after administration of the last dose. The clinical relevance of this suppression of histamine-induced wheal and flare response on skin testing is unknown.
The effects of intradermal injection of various other mediators or histamine releasers were also inhibited by Cetirizine, as was response to a cold challenge in patients with cold-induced urticaria. In mildly asthmatic subjects, Cetirizine hydrochloride at 5 to 20 mg blocked bronchoconstriction due to nebulized histamine, with virtually total blockade after a 20 mg dose. In studies conducted for up to 12 hours following cutaneous antigen challenge, the late phase recruitment of eosinophils, neutrophils and basophils, components of the allergic inflammatory response, was inhibited by Cetirizine hydrochloride at a dose of 20 mg.
In four clinical studies in healthy adult males, no clinically significant mean increases in QTc were observed in Cetirizine hydrochloride treated subjects. In the first study, a placebo-controlled crossover trial, Cetirizine hydrochloride was given at doses up to 60 mg per day, 6 times the maximum clinical dose, for 1 week, and no significant mean QTc prolongation occurred. In the second study, a crossover trial, Cetirizine hydrochloride 20 mg and erythromycin (500 mg every 8 hours) were given alone and in combination. There was no significant effect on QTc with the combination or with Cetirizine hydrochloride alone. In the third trial, also a crossover study, Cetirizine hydrochloride 20 mg and ketoconazole (400 mg per day) were given alone and in combination. Cetirizine hydrochloride caused a mean increase in QTc of 9.1 msec from baseline after 10 days of therapy. Ketoconazole also increased QTc by 8.3 msec. The combination caused an increase of 17.4 msec, equal to the sum of the individual effects. Thus, there was no significant drug interaction on QTc with the combination of Cetirizine hydrochloride and ketoconazole. In the fourth study, a placebo-controlled parallel trial, Cetirizine hydrochloride 20 mg was given alone or in combination with azithromycin (500 mg as a single dose on the first day followed by 250 mg once daily). There was no significant increase in QTc with Cetirizine hydrochloride 20 mg alone or in combination with azithromycin.
In a four-week clinical trial in pediatric patients aged 6 to 11 years, results of randomly obtained ECG measurements before treatment and after 2 weeks of treatment showed that Cetirizine hydrochloride 5 or 10 mg did not increase QTc versus placebo. In a one week clinical trial (N = 86) of Cetirizine hydrochloride syrup (0.25 mg/kg bid) compared with placebo in pediatric patients 6 to 11 months of age, ECG measurements taken within 3 hours of the last dose did not show any ECG abnormalities or increases in QTc interval in either group compared to baseline assessments. Data from other studies where Cetirizine hydrochloride was administered to patients 6 to 23 months of age were consistent with the findings in this study.
The effects of Cetirizine hydrochloride on the QTc interval at doses higher than 10 mg have not been studied in children less than 12 years of age.
In a six-week, placebo-controlled study of 186 patients (aged 12 to 64 years) with allergic rhinitis and mild to moderate asthma, Cetirizine hydrochloride 10 mg once daily improved rhinitis symptoms and did not alter pulmonary function. In a two-week, placebo-controlled clinical trial, a subset analysis of 65 pediatric (aged 6 to 11 years) allergic rhinitis patients with asthma showed Cetirizine hydrochloride did not alter pulmonary function. These studies support the safety of administering Cetirizine hydrochloride to pediatric and adult allergic rhinitis patients with mild to moderate asthma.
Clinical StudiesMulticenter, randomized, double-blind, clinical trials comparing Cetirizine 5 to 20 mg to placebo in patients 12 years and older with perennial allergic rhinitis were conducted in the United States. Two of these showed significant reductions in symptoms of perennial allergic rhinitis for up to 8 weeks in duration. Two 4 week multicenter, randomized, double-blind, clinical trials comparing Cetirizine 5 to 20 mg to placebo in patients with chronic idiopathic urticaria were also conducted and showed significant improvement in symptoms of chronic idiopathic urticaria. In general, the 10 mg dose was more effective than the 5 mg dose and the 20 mg dose gave no added effect. Some of these trials included pediatric patients aged 12 to 16 years. In addition, four multicenter, randomized, placebo-controlled, double-blind 2 to 4 week trials in 534 pediatric patients aged 6 to 11 years with seasonal allergic rhinitis were conducted in the United States at doses up to 10 mg.
Indications and Usage for Cetirizine Perennial Allergic RhinitisCetirizine hydrochloride is indicated for the relief of symptoms associated with perennial allergic rhinitis due to allergens such as dust mites, animal dander and molds in children 6 to 23 months of age. Symptoms treated effectively include sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, and tearing.
Chronic UrticariaCetirizine hydrochloride is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in children 6 months to 5 years of age. It significantly reduces the occurrence, severity, and duration of hives and significantly reduces pruritus.
ContraindicationsCetirizine hydrochloride syrup is contraindicated in those patients with a known hypersensitivity to Cetirizine hydrochloride or any of its ingredients or hydroxyzine.
Precautions Activities Requiring Mental AlertnessIn clinical trials, the occurrence of somnolence has been reported in some patients taking Cetirizine hydrochloride; due caution should therefore be exercised when driving a car or operating potentially dangerous machinery. Concurrent use of Cetirizine hydrochloride with alcohol or other CNS depressants should be avoided because additional reductions in alertness and additional impairment of CNS performance may occur.
Drug-Drug InteractionsNo clinically significant drug interactions have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin. There was a small decrease in the clearance of Cetirizine caused by a 400 mg dose of theophylline; it is possible that larger theophylline doses could have a greater effect.
Carcinogenesis, Mutagenesis, Impairment of FertilityIn a 2 year carcinogenicity study in rats, Cetirizine was not carcinogenic at dietary doses up to 20 mg/kg (approximately 15 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 7 times the maximum recommended daily oral dose in infants on a mg/m2 basis). In a 2 year carcinogenicity study in mice, Cetirizine caused an increased incidence of benign liver tumors in males at a dietary dose of 16 mg/kg (approximately 6 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 3 times the maximum recommended daily oral dose in infants on a mg/m2 basis). No increase in the incidence of liver tumors was observed in mice at a dietary dose of 4 mg/kg (approximately 2 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately equivalent to the maximum recommended daily oral dose in infants on a mg/m2 basis). The clinical significance of these findings during long-term use of Cetirizine hydrochloride is not known.
Cetirizine was not mutagenic in the Ames test, and not clastogenic in the human lymphocyte assay, the mouse lymphoma assay, and in vivo micronucleus test in rats.
In a fertility and general reproductive performance study in mice, Cetirizine did not impair fertility at an oral dose of 64 mg/kg (approximately 25 times the maximum recommended daily oral dose in adults on a mg/m2 basis).
Pediatric UseThe safety of Cetirizine hydrochloride has been demonstrated in pediatric patients aged 6 months to 5 years. The safety of Cetirizine has been demonstrated in 168 patients aged 2 to 5 years in placebo controlled trials of up to 4 weeks duration. On a mg/kg basis, most of the 168 patients received between 0.2 and 0.4 mg/kg of Cetirizine HCl. The safety of Cetirizine in 399 patients aged 12 to 24 months has been demonstrated in a placebo-controlled 18 month trial, in which the average dose was 0.25 mg/kg bid, corresponding to a range of 4 to 11 mg/day. The safety of Cetirizine hydrochloride syrup has been demonstrated in 42 patients aged 6 to 11 months in a placebo-controlled 7 day trial. The prescribed dose was 0.25 mg/kg bid, which corresponded to a mean of 4.5 mg/day, with a range of 3.4 to 6.2 mg/day.
The effectiveness of Cetirizine hydrochloride for the treatment of allergic rhinitis and chronic idiopathic urticaria in pediatric patients aged 6 months to 5 years is based on an extrapolation of the demonstrated efficacy of Cetirizine hydrochloride in adults with these conditions and the likelihood that the disease course, pathophysiology and the drug’s effect are substantially similar between these two populations. Efficacy is extrapolated down to 6 months of age for perennial allergic rhinitis because this disease is thought to occur down to these ages in children. The recommended doses for the pediatric population are based on cross-study comparisons of the pharmacokinetics and pharmacodynamics of Cetirizine in adult and pediatric subjects and on the safety profile of Cetirizine in both adult and pediatric patients at doses equal to or higher than the recommended doses. The Cetirizine AUC and Cmax in pediatric subjects aged 6 to 23 months who received a mean of 2.3 mg in a single dose and in subjects aged 2 to 5 years who received a single dose of 5 mg of Cetirizine syrup, was estimated to be intermediate between that observed in adults who received a single dose of 10 mg of Cetirizine tablets and those who received a single dose of 20 mg of Cetirizine tablets.
The safety and effectiveness of Cetirizine in pediatric patients under the age of 6 months have not been established.
Adverse ReactionsPediatric studies were conducted with Cetirizine hydrochloride. More than 1300 pediatric patients aged 6 to 11 years with more than 900 treated with Cetirizine hydrochloride at doses of 1.25 to 10 mg per day were included in controlled and uncontrolled clinical trials conducted in the United States. The duration of treatment ranged from 2 to 12 weeks. Placebo-controlled trials up to 4 weeks duration included 168 pediatric patients aged 2 to 5 years who received Cetirizine, the majority of whom received single daily doses of 5 mg. A placebo-controlled trial 18 months in duration included 399 patients aged 12 to 24 months treated with Cetirizine (0.25 mg/kg bid), and another placebo-controlled trial of 7 days duration included 42 patients aged 6 to 11 months who were treated with Cetirizine (0.25 mg/kg bid).
The majority of adverse reactions reported in pediatric patients aged 2 to 11 years with Cetirizine hydrochloride were mild or moderate. In placebo-controlled trials, the incidence of discontinuations due to adverse reactions in pediatric patients receiving up to 10 mg of Cetirizine hydrochloride was uncommon (0.4% on Cetirizine hydrochloride vs. 1.0% on placebo).
Table 1 lists adverse experiences which were reported for Cetirizine hydrochloride 5 and 10 mg in pediatric patients aged 6 to 11 years in placebo-controlled clinical trials in the United States and were more common with Cetirizine hydrochloride than placebo. Of these, abdominal pain was considered treatment-related and somnolence appeared to be dose-related, 1.3% in placebo, 1.9% at 5 mg and 4.2% at 10 mg. The adverse experiences reported in pediatric patients aged 2 to 5 years in placebo-controlled trials were qualitatively similar in nature and generally similar in frequency to those reported in trials with children aged 6 to 11 years.
In the placebo-controlled trials of pediatric patients 6 to 24 months of age, the incidences of adverse experiences, were similar in the Cetirizine and placebo treatment groups in each study. Somnolence occurred with essentially the same frequency in patients who received Cetirizine and patients who received placebo. In a study of 1 week duration in children 6 to 11 months of age, patients who received Cetirizine exhibited greater irritability/fussiness than patients on placebo. In a study of 18 months duration in patients 12 months and older, insomnia occurred more frequently in patients who received Cetirizine compared to patients who received placebo (9.0% v. 5.3%). In those patients who received 5 mg or more per day of Cetirizine as compared to patients who received placebo, fatigue (3.6% v. 1.3%) and malaise (3.6% v. 1.8%) occurred more frequently.
Table 1. Adverse Experiences Reported in Pediatric Patients Aged 6 to 11 Years in Placebo-Controlled United States Cetirizine Hydrochloride Trials (5 or 10 mg Dose) Which Occurred at a Frequency of ? 2% in Either the 5 mg or the 10 mg Cetirizine Hydrochloride Group, and More Frequently Than in the Placebo Group Adverse Experiences Placebo (N = 309) Cetirizine Hydrochloride 5 mg (N = 161) 10 mg (N = 215) Headache 12.3% 11.0% 14.0% Pharyngitis 2.9% 6.2% 2.8% Abdominal pain 1.9% 4.4% 5.6% Coughing 3.9% 4.4% 2.8% Somnolence 1.3% 1.9% 4.2% Diarrhea 1.3% 3.1% 1.9% Epistaxis 2.9% 3.7% 1.9% Bronchospasm 1.9% 3.1% 1.9% Nausea 1.9% 1.9% 2.8% Vomiting 1.0% 2.5% 2.3%The following events were observed infrequently (less than 2%), in either 3982 adults and children 12 years and older or in 659 pediatric patients aged 6 to 11 years who received Cetirizine hydrochloride in U.S. trials, including an open adult study of six months duration. A causal relationship of these infrequent events with Cetirizine hydrochloride administration has not been established.
Autonomic Nervous System: anorexia, flushing, increased salivation, urinary retention.
Cardiovascular: cardiac failure, hypertension, palpitation, tachycardia.
Central and Peripheral Nervous Systems: abnormal coordination, ataxia, confusion, dysphonia, hyperesthesia, hyperkinesia, hypertonia, hypoesthesia, leg cramps, migraine, myelitis, paralysis, paresthesia, ptosis, syncope, tremor, twitching, vertigo, visual field defect.
Gastrointestinal: abnormal hepatic function, aggravated tooth caries, constipation, dyspepsia, eructation, flatulence, gastritis, hemorrhoids, increased appetite, melena, rectal hemorrhage, stomatitis including ulcerative stomatitis, tongue discoloration, tongue edema.
Genitourinary: cystitis, dysuria, hematuria, micturition frequency, polyuria, urinary incontinence, urinary tract infection.
Hearing and Vestibular: deafness, earache, ototoxicity, tinnitus.
Metabolic/Nutritional: dehydration, diabetes mellitus, thirst.
Musculoskeletal: arthralgia, arthritis, arthrosis, muscle weakness, myalgia.
Psychiatric: abnormal thinking, agitation, amnesia, anxiety, decreased libido, depersonalization, depression, emotional lability, euphoria, impaired concentration, insomnia, nervousness, paroniria, sleep disorder.
Respiratory System: bronchitis, dyspnea, hyperventilation, increased sputum, pneumonia, respiratory disorder, rhinitis, sinusitis, upper respiratory tract infection.
Reproductive: dysmenorrhea, female breast pain, intermenstrual bleeding, leukorrhea, menorrhagia, vaginitis.
Reticuloendothelial: lymphadenopathy.
Skin: acne, alopecia, angioedema, bullous eruption, dermatitis, dry skin, eczema, erythematous rash, furunculosis, hyperkeratosis, hypertrichosis, increased sweating, maculopapular rash, photosensitivity reaction, photosensitivity toxic reaction, pruritus, purpura, rash, seborrhea, skin disorder, skin nodule, urticaria.
Special Senses: parosmia, taste loss, taste perversion.
Vision: blindness, conjunctivitis, eye pain, glaucoma, loss of accommodation, ocular hemorrhage, xerophthalmia.
Body as a Whole: accidental injury, asthenia, back pain, chest pain, enlarged abdomen, face edema, fever, generalized edema, hot flashes, increased weight, leg edema, malaise, nasal polyp, pain, pallor, periorbital edema, peripheral edema, rigors.
Occasional instances of transient, reversible hepatic transaminase elevations have occurred during Cetirizine therapy. Hepatitis with significant transaminase elevation and elevated bilirubin in association with the use of Cetirizine hydrochloride has been reported.
Postmarketing ExperienceIn the postmarketing period, the following additional rare, but potentially severe adverse events have been reported: aggressive reaction, anaphylaxis, cholestasis, convulsions, glomerulonephritis, hallucinations, hemolytic anemia, hepatitis, orofacial dyskinesia, severe hypotension, stillbirth, suicidal ideation, suicide and thrombocytopenia.
Drug Abuse and DependenceThere is no information to indicate that abuse or dependency occurs with Cetirizine hydrochloride.
OverdosageOverdosage has been reported with Cetirizine hydrochloride. In one adult patient who took 150 mg of Cetirizine hydrochloride, the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematology results. In an 18 month old pediatric patient who took an overdose of Cetirizine hydrochloride (approximately 180 mg), restlessness and irritability were observed initially; this was followed by drowsiness. Should overdose occur, treatment should be symptomatic or supportive, taking into account any concomitantly ingested medications. There is no known specific antidote to Cetirizine hydrochloride. Cetirizine hydrochloride is not effectively removed by dialysis, and dialysis will be ineffective unless a dialyzable agent has been concomitantly ingested. The acute minimal lethal oral doses were 237 mg/kg in mice (approximately 95 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 40 times the maximum recommended daily oral dose in infants on a mg/m2 basis) and 562 mg/kg in rats (approximately 460 times the maximum recommended daily oral dose in adults on a mg/m2 basis, or approximately 190 times the maximum recommended daily oral dose in infants on a mg/m2 basis). In rodents, the target of acute toxicity was the central nervous system, and the target of multiple-dose toxicity was the liver.
Cetirizine Dosage and AdministrationCetirizine hydrochloride syrup can be taken without regard to food consumption.
Children 2 to 5 Years for Chronic UrticariaThe recommended initial dose of Cetirizine hydrochloride syrup in children aged 2 to 5 years is 2.5 mg (? teaspoonful) syrup once daily. The dosage in this age group can be increased to a maximum dose of 5 mg per day given as 1 teaspoonful syrup once a day, or one ? teaspoonful syrup given every 12 hours.
Children 6 months to < 2 years for Perennial Allergic Rhinitis and Chronic UrticariaThe recommended dose of Cetirizine hydrochloride syrup in children 6 months to 23 months of age is 2.5 mg (? teaspoonful) once daily. The dose in children 12 to 23 months of age can be increased to a maximum dose of 5 mg per day, given as ? teaspoonful (2.5 mg) every 12 hours.
How is Cetirizine SuppliedCetirizine hydrochloride syrup is colorless to slightly yellow with a banana flavor. Each teaspoonful (5 mL) contains 5 mg Cetirizine hydrochloride. Cetirizine hydrochloride syrup is available in 4 ounce and 16 ounce bottles.
Store at 20° to 25°C (68° to 77°F)[See USP Controlled Room Temperature].
Manufactured By:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Rev. C 5/2008
PRINCIPAL DISPLAY PANEL Cetirizine Hydrochloride Syrup 1 mg/mL 4 oz Label TextNDC 0093-6300-12
Cetirizine
HYDROCHLORIDE
Syrup
1 mg/mL*
FOR ORAL USE ONLY
Rx only
4 OZ
TEVA
Cetirizine HYDROCHLORIDE
Cetirizine hydrochloride syrup Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0093-6300 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Cetirizine HYDROCHLORIDE (Cetirizine) Cetirizine HYDROCHLORIDE 1 mg in 1 mL Inactive Ingredients Ingredient Name Strength ACETIC ACID GLYCERIN METHYLPARABEN PROPYLENE GLYCOL PROPYLPARABEN WATER SACCHARIN SODIUM SODIUM ACETATE SUCROSE Product Characteristics Color Score Shape Size Flavor BANANA Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 0093-6300-12 120 mL In 1 BOTTLE None 2 0093-6300-16 473 mL In 1 BOTTLE None
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077279 01/15/2012
Labeler - Teva Pharmaceuticals USA Inc (118234421) Revised: 01/2012Teva Pharmaceuticals USA Inc
Stavzor
valproic acid
Dosage Form: capsule, delayed release
FULL PRESCRIBING INFORMATION
WARNING: LIFE-THREATENING ADVERSE REACTIONS
Hepatotoxicity
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Children under the age of 2 years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When Stavzor is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. The incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
These incidents usually have occurred during the first 6 months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first 6 months [see Warnings and Precautions (5.1)].
Teratogenicity
Valproate can produce teratogenic effects such as neural tube defects (eg. spina bifida). Accordingly, the use of Stavzor in women of childbearing potential requires that the benefits of its use be weighed against the risk of injury to the fetus. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (eg. migraine) is contemplated. [see Warnings and Precautions (5.2)].
An information sheet describing the teratogenic potential of valproate is available for patients. [see Patient Counseling Information (17)].
Pancreatitis
Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with a rapid progression from initial symptoms to death. Cases have been reported shortly after initial use as well as after several years of use. Patients and guardians should be warned that abdominal pain, nausea, vomiting and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated [see warnings and precautions (5.3)] .
Indications and Usage for Stavzor ManiaStavzor™ (valproic acid) delayed release capsules are indicated for the treatment of the manic episodes associated with bipolar disorder. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility.
The efficacy of valproate was established in 3-week trials with patients meeting DSM-III-R criteria for bipolar disorder who were hospitalized for acute mania [see Clinical Studies (14.1)].
The safety and effectiveness of valproate for long-term use in mania, i.e., more than 3 weeks, has not been systematically evaluated in controlled clinical trials. Therefore, physicians who elect to use Stavzor (valproic acid) delayed release capsules for extended periods should continually reevaluate the long-term usefulness of the drug for the individual patient.
EpilepsyStavzor is indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. Stavzor is also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.
Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present.
MigraineStavzor is indicated for prophylaxis of migraine headaches. There is no evidence that Stavzor is useful in the acute treatment of migraine headaches. Because it may be a hazard to the fetus, Stavzor should be considered for women of childbearing potential only after this risk has been thoroughly discussed with the patient and weighed against the potential benefits of treatment [see Warnings and Precautions (5.2), Patient Counseling Information (17.3)].
DOSAGE & ADMINISTRATION ManiaStavzor (valproic acid) delayed release capsules are administered orally, and must be swallowed whole. The recommended initial dose is 750 mg daily in divided doses. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose which produces the desired clinical effect or the desired range of plasma concentrations. In placebo-controlled clinical trials of acute mania, patients were dosed to a clinical response with a trough plasma concentration between 50 and 125 mcg/mL. Maximum concentrations were generally achieved within 14 days. The maximum recommended dosage is 60 mg/kg/day.
There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during Stavzor treatment of an acute manic episode. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the benefits of Stavzor in such longer-term treatment. Although there are no efficacy data that specifically address longer-term antimanic treatment with Stavzor, the safety of Stavzor in long-term use is supported by data from record reviews involving approximately 360 patients treated with valproate for greater than 3 months.
EpilepsyStavzor (valproic acid) delayed release capsules are administered orally, and must be swallowed whole. As Stavzor dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions (7.2)] .
Complex Partial Seizures
For adults and children 10 years of age or older.
Monotherapy (Initial Therapy)
Valproate has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made.
The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 mcg/mL in females and 135 mcg/mL in males. The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
Conversion to Monotherapy
Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 - 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. Concomitant antiepilepsy drug (AED) dosage can ordinarily be reduced by approximately 25% every 2 weeks. This reduction may be started at initiation of Stavzor therapy, or delayed by 1 to 2 weeks if there is a concern that seizures are likely to occur with a reduction. The speed and duration of withdrawal of the concomitant AED can be highly variable, and patients should be monitored closely during this period for increased seizure frequency.
Adjunctive Therapy
Stavzor may be added to the patient's regimen at a dosage of 10 to 15 mg/kg/day. The dosage may be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 mcg/mL). No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. If the total daily dose exceeds 250 mg, it should be given in 2 to 3 doses.
In a study of adjunctive therapy for complex partial seizures in which patients were receiving either carbamazepine or phenytoin in addition to valproate, no adjustment of carbamazepine or phenytoin dosage was needed [see Clinical studies Studies (14.3)] . However, since valproate may interact with these or other concurrently administered AEDs as well as other drugs, periodic plasma concentration determinations of concomitant AEDs are recommended during the early course of therapy [see Drug Interactions (7)].
Simple and Complex Absence Seizures
The recommended initial dose is 15 mg/kg/day, increasing at 1-week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. The maximum recommended dosage is 60 mg/kg/day. If the total daily dose exceeds 250 mg, it should be given in 2 to 3 doses.
A good correlation has not been established between daily dose, serum concentrations, and therapeutic effect. However, therapeutic valproate serum concentrations for most patients with absence seizures are considered to range from 50 to 100 mcg/mL. Some patients may be controlled with lower or higher serum concentrations [see Clinical Pharmacology (12.3)].
As Stavzor dosage is titrated upward, blood concentrations of phenobarbital and/or phenytoin may be affected [see Drug Interactions (7.2)].
Antiepilepsy drugs should not be abruptly discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.
In epileptic patients previously receiving Depakene (valproic acid) therapy, Stavzor should be initiated at the same daily dose and dosing schedule. After the patient is stabilized on Stavzor, a dosing schedule of 2 or 3 times a day may be elected in selected patients.
MigraineStavzor (valproic acid) delayed release capsules are administered orally, and must be swallowed whole. The recommended starting dose is 250 mg twice daily. Some patients may benefit from doses up to 1000 mg/day. In clinical trials, there was no evidence that higher doses led to greater efficacy.
General Dosing AdviceDosing in Elderly Patients
Due to a decrease in unbound clearance of valproate and possibly a greater sensitivity to somnolence in the elderly, the starting dose should be reduced in these patients. Dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence. The ultimate therapeutic dose should be achieved on the basis of both tolerability and clinical response [see Warnings and Precautions (5.12)].
Dose-Related Adverse Reactions
The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose- related. The probability of thrombocytopenia appears to increase significantly at total valproate concentrations of ? 110 mcg/mL (females) or ? 135 mcg/mL (males) [see Warnings and Precautions (5.6)] . The benefit of improved therapeutic effect with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
G.I. Irritation
Patients who experience G.I. irritation may benefit from administration of the drug with food or by slowly building up the dose from an initial low level.
DOSAGE FORMS & STRENGTHS 125-mg orange-colored, oval-shaped capsules with NVN in black print 250-mg orange-colored, oval-shaped capsules with NVN1 in black print 500-mg orange-colored, oval-shaped capsules with NVN2 in black print Contraindications Stavzor should not be administered to patients with hepatic disease or significant hepatic dysfunction. [see Warnings and Precautions (5.1)]. Stavzor is contraindicated in patients with known hypersensitivity to the drug. [see Warnings and Precautions (5.10)]. Stavzor is contraindicated in patients with known urea cycle disorders [see Warnings and Precautions (5.4)]. Warnings and Precautions HepatotoxicityHepatic failure resulting in fatalities has occurred in patients receiving valproic acid. These incidents usually have occurred during the first 6 months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six 6 months. However, physicians should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination.
Caution should be observed when administering valproic acid products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. Experience has indicated that children under the age of two 2 years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions. When Stavzor is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of drug. [see Boxed Warning and Contraindications (4)] .
Teratogenicity/Usage in PregnancyUse of Stavzor during pregnancy can cause congenital malformations including neural tube defects. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Stavzor should be considered for women of childbearing potential only after the risks have been thoroughly discussed with the patient and weighed against the potential benefits of treatment.
Data suggest that there is an increased incidence of congenital malformations associated with the use of valproate by women with seizure disorders during pregnancy when compared to the incidence in women with seizure disorders who do not use antiepileptic drugs during pregnancy, the incidence in women with seizure disorders who use other antiepileptic drugs, and the background incidence for the general population.
There are multiple reports in the clinical literature that indicate the use of antiepileptic drugs during pregnancy results in an increased incidence of congenital malformations in offspring. Antiepileptic drugs, including valproate, should be administered to women of childbearing potential only if they are clearly shown to be essential in the management of their medical condition.
Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. [see Boxed Warning and Contraindications (8.1)].
PancreatitisCases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. Some cases have occurred shortly after initial use as well as after several years of use. The rate based upon the reported cases exceeds that expected in the general population and there have been cases in which pancreatitis recurred after rechallenge with valproate. In clinical trials, there were 2 cases of pancreatitis without alternative etiology in 2416 patients, representing 1044 patient-years experience. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, Stavzor should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated. [see Boxed Warning].
Urea cycle DisordersStavzor is contraindicated in patients with known urea cycle disorders (UCD). Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with UCD, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of Stavzor therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low blood urea nitrogen (BUN), or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs or symptoms of UCD. Patients who develop symptoms of unexplained hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment (including discontinuation of valproate therapy) and be evaluated for underlying UCD. [see Contraindications (4) and Warnings and Precautions (5.8)].
Suicidal Behavior and IdeationAntiepileptic drugs (AEDs), including Stavzor, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
Table 1 Risk by indication for antiepileptic drugs in the pooled analysis Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Stavzor or any other AED must balance the risk of suicidal thoughts and behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
ThrombocytopeniaThe frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose- related. In a clinical trial of valproate as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ?75 x 109%L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ? 110 mcg/mL (females) or ? 135 mcg%mL (males). The therapeutic benefit which may accompany the higher doses should therefore be weighed against the possibility of a greater incidence of adverse effects.
Because of reports of thrombocytopenia [see Warnings and Precautions (5.6)] , inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (eg, low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving Stavzor be monitored for platelet count and coagulation parameters prior to planned surgery. In a clinical trial of valproate as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ? 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ?110 mcg/mL (females) or ?135 mcg/mL (males). Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy.
HyperammonemiaHyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. Hyperammonemia should also be considered in patients who present with hypothermia [see Warnings and Precautions (5.9)]
If ammonia is increased, valproate therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders [see Contraindications (4) and Warnings and Precautions (5.4, 5.7)].
Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered .
Hyperammonemia and Encephalopathy Associated With Concomitant Topiramate UseConcomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. Clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. Hypothermia can also be a manifestation of hyperammonemia [see Warnings and Precautions (5.9)].
In most cases, symptoms and signs abated with discontinuation of either drug. This adverse event is not due to a pharmacokinetic interaction. It is not known if topiramate monotherapy is associated with hyperammonemia. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy. Although not studied, an interaction of topiramate and valproic acid may exacerbate existing defects or unmask deficiencies in susceptible persons. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured [see Contraindications (4) and Warnings and Precautions (5.7)].
5.9 HypothermiaHypothermia, defined as an unintentional drop in body core temperature to <35° C (95° F), has been reported in association with valproate therapy both in conjunction with and in the absence of hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate with valproate after starting topiramate treatment or after increasing the daily dose of topiramate [see Drug Interactions (7.3)] . Consideration should be given to stopping valproate in patients who develop hypothermia, which may be manifested by a variety of clinical abnormalities including lethargy, confusion, coma, and significant alterations in other major organ systems such as the cardiovascular and respiratory systems. Clinical management and assessment should include examination of blood ammonia levels.
Multi-Organ Hypersensitivity ReactionsMulti-organ hypersensitivity reactions have been rarely reported in close temporal association to the initiation of valproate therapy in adult and pediatric patients (median time to detection 21 days: range 1 to 40 days). Although there have been a limited number of reports, many of these cases resulted in hospitalization and at least one death has been reported. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations may include lymphadenopathy, hepatitis, liver function test abnormalities, hematological abnormalities (eg. eosinophilia, thrombocytopenia, neutropenia), pruritus, nephritis, oliguria, hepato-renal syndrome, arthralgia, and asthenia. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, valproate should be discontinued and an alternative treatment started. Although the existence of cross sensitivity with other drugs that produce this syndrome is unclear, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility.
5.11 Interaction with Carbapenem AntibioticsCarbapenem antibiotics (ertapenem, imipenem, meropenem) may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations drop significantly or seizure control deteriorates [see Drug Interactions (7.1)] .
Somnolence in the ElderlyIn a double-blind, multicenter trial of valproate in elderly patients with dementia (mean age = 83 years), doses were increased by 125 mg/day to a target dose of 20 mg/kg/day. A significantly higher proportion of valproate patients had somnolence compared to placebo, and although not statistically significant, there was a higher proportion of patients with dehydration. Discontinuations for somnolence were also significantly higher than with placebo. In some patients with somnolence (approximately one-half), there was associated reduced nutritional intake and weight loss. There was a trend for the patients who experienced these events to have a lower baseline albumin concentration, lower valproate clearance, and a higher BUN. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse reactions. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence [see Dosage and Administration (2.4)].
Monitoring: Drug Plasma ConcentrationSince valproic acid may interact with concurrently administered drugs which are capable of enzyme induction, periodic plasma concentration determinations of valproate and concomitant drugs are recommended during the early course of therapy [see Drug Interactions (7)] .
5.14 Effect on Ketone and Thyroid Function TestsValproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test.
There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown.
Effect on HIV and CMV Viruses ReplicationThere are in vitro studies that suggest valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequence, if any, is not known. Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. Nevertheless, these data should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV-infected patients receiving valproate or when following CMV-infected patients clinically.
Adverse ReactionsBecause clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
6.1 ManiaThe incidence of treatment-emergent events has been ascertained based on combined data from 2 placebo-controlled clinical trials of valproate in the treatment of manic episodes associated with bipolar disorder. The adverse events were usually mild or moderate in intensity, but sometimes were serious enough to interrupt treatment. In clinical trials, the rates of premature termination due to intolerance were not statistically different between placebo, valproate, and lithium carbonate. A total of 4%, 8% and 11% of patients discontinued therapy due to intolerance in the placebo, valproate , and lithium carbonate groups, respectively.
Table 2 summarizes those adverse events reported for patients in these trials where the incidence rate in the valproate -treated group was greater than 5% and greater than the placebo incidence, or where the incidence in the valproate -treated group was statistically significantly greater than the placebo group. Vomiting was the only event that was reported by significantly (p ? 0.05) more patients receiving valproate compared to placebo.
Table 2.Adverse Reactions Reported by > 5% of Valproate –Treated Patients During Placebo –Controlled Trials of Acute Maniaa Adverse Event Valproate(n=89) Placebo
(n=97) a. The following adverse events occurred at an equal or greater incidence for placebo than for valproate: back pain, headache, constipation, diarrhea, tremor, and pharyngitis. Nausea 22% 15% Somnolence 19% 12% Dizziness 12% 4% Vomiting 12% 3% Asthenia 10% 7% Abdominal Pain 9% 8% Dyspepsia 9% 8% Rash 6% 3%
The following additional adverse events were reported by greater than 1% but not more than 5% of the 89 valproate-treated patients in controlled clinical trials:
Body as a Whole: Chest pain, chills, chills and fever, fever, neck pain, neck rigidity.
Cardiovascular System: Hypertension, hypotension, palpitations, postural hypotension, tachycardia, vasodilation.
Digestive System: Anorexia, fecal incontinence, flatulence, gastroenteritis, glossitis, periodontal abscess.
Hemic and Lymphatic System: Ecchymosis.
Metabolic and Nutritional Disorders: Edema, peripheral edema.
Musculoskeletal System: Arthralgia, arthrosis, leg cramps, twitching.
Nervous System: Abnormal dreams, abnormal gait, agitation, ataxia, catatonic reaction, confusion, depression, diplopia, dysarthria, hallucinations, hypertonia, hypokinesia, insomnia, paresthesia, reflexes increased, tardive dyskinesia, thinking abnormalities, vertigo.
Respiratory System: Dyspnea, rhinitis.
Skin and Appendages: Alopecia, discoid lupus erythematosis, dry skin, furunculosis, maculopapular rash, seborrhea.
Special Senses: Amblyopia, conjunctivitis, deafness, dry eyes, ear pain, eye pain, tinnitus.
Urogenital System: Dysmenorrhea, dysuria, urinary incontinence.
6.2 EpilepsyBased on a placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures, valproate was generally well tolerated with most adverse events rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the valproate -treated patients (6%), compared to 1% of placebo-treated patients.
Table 3 lists treatment-emergent adverse events which were reported by ? 5% of valproate -treated patients and for which the incidence was greater than in the placebo group, in the placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse events can be ascribed to valproate alone, or the combination of valproate and other antiepilepsy drugs.
Table 3. Adverse Reactions Reported by > 5% of Patients Treated with Valproate During Placebo-Controlled Trial of Adjunctive Therapy for Complex Partial Seizures Body System/Event Valproate (%)(n = 77) Placebo (%)
(n = 70) Body as a Whole Headache 31 21 Asthenia 27 7 Fever 6 4 Gastrointestinal System Nausea 48 14 Vomiting 27 7 Abdominal pain 23 6 Diarrhea 13 6 Anorexia 12 0 Dyspepsia 8 4 Constipation 5 1 Nervous System Somnolence 27 11 Tremor 25 6 Dizziness 25 13 Diplopia 16 9 Amblyopia/Blurred Vision 12 9 Ataxia 8 1 Nystagmus 8 1 Emotional Lability 6 4 Thinking Abnormal 6 0 Amnesia 5 1 Respiratory System Flu Syndrome 12 9 Infection 12 6 Bronchitis 5 1 Rhinitis 5 4 Other Alopecia 6 1 Weight Loss 6 0
Table 4 lists treatment-emergent adverse events which were reported by ? 5% of patients in the high dose valproate group, and for which the incidence was greater than in the low dose group, in a controlled trial of valproate monotherapy treatment of complex partial seizures. Since patients were being titrated off another antiepilepsy drug during the first portion of the trial, it is not possible, in many cases, to determine whether the following adverse events can be ascribed to valproate alone, or the combination of valproate and other antiepilepsy drugs.
Table 4. Adverse Reactions Reported by > 5% of Patients in the High-Dose Group in the Controlled Trial of Valproate Monotherapy for Complex Partial Seizuresa Body System/Event High Dose (%)(n = 131) Low Dose (%)
(n = 134) a. Headache was the only adverse event that occurred in ? 5% of patients in the high-dose group and at an equal or greater incidence in the low-dose group. Body as a Whole Asthenia 21 10 Digestive System Nausea 34 26 Diarrhea 23 19
Zoladex 3-Month
Dosage Form: implant 10.8 mg - 12 week
FULL PRESCRIBING INFORMATION
Indications and Usage for Zoladex 3-Month
Stage B2-C Prostatic Carcinoma
ZOLADEX is indicated for use in combination with flutamide for the management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate. Treatment with ZOLADEX and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy [see Dosage and Administration (2.1) and Clinical Studies (14.1)].
Prostatic CarcinomaZOLADEX is indicated in the palliative treatment of advanced carcinoma of the prostate [see Dosage and Administration (2.2) and Clinical Studies (14.2)].
In controlled studies of patients with advanced prostatic cancer comparing ZOLADEX 3.6 mg to orchiectomy, the long-term endocrine responses and objective responses were similar between the two treatment arms. Additionally, duration of survival was similar between the two treatment arms in a major comparative trial.
In controlled studies of patients with advanced prostatic cancer, ZOLADEX 10.8 mg implant produced pharmacodynamically similar effect in terms of suppression of serum testosterone to that achieved with ZOLADEX 3.6 mg implant. Clinical outcome similar to that produced with the use of the ZOLADEX 3.6 mg implant administered every 28 days is predicted with the ZOLADEX 10.8 mg implant administered every 12 weeks.
The automatic safety feature of the syringe aids in the prevention of needlestick injury.
Zoladex 3-Month Dosage and AdministrationZOLADEX, at a dose of 10.8 mg, should be administered subcutaneously every 12 weeks into the anterior abdominal wall below the navel line using an aseptic technique under the supervision of a physician [see Dosage and Administration (2.5)].
While a delay of a few days is permissible, every effort should be made to adhere to the 12-week schedule.
Stage B2-C Prostatic CarcinomaWhen ZOLADEX is given in combination with radiotherapy and flutamide for patients with Stage T2b-T4 (Stage B2-C) prostatic carcinoma, treatment should be started 8 weeks prior to initiating radiotherapy and should continue during radiation therapy. A treatment regimen using one ZOLADEX 3.6 mg depot, followed in 28 days by one ZOLADEX 10.8 mg depot, should be administered.
Prostatic CarcinomaFor the management of advanced prostate cancer, ZOLADEX is intended for long-term administration unless clinically inappropriate.
Renal or Hepatic ImpairmentNo dosage adjustment is necessary for patients with renal or hepatic impairment.
WomenZOLADEX 10.8 mg implant is not indicated in women as the data are insufficient to support reliable suppression of serum estradiol. For female patients requiring treatment with goserelin, refer to prescribing information for ZOLADEX 3.6 mg implant.
Administration TechniqueThe proper method of administration of ZOLADEX is described in the instructions that follow.
1. Put the patient in a comfortable position with the upper part of the body slightly raised. Prepare an area of the anterior abdominal wall below the navel line with an alcohol swab.
2. Examine the foil pouch and syringe for damage. Remove the syringe from the opened foil pouch and hold the syringe at a slight angle to the light. Check that at least part of the ZOLADEX implant is visible.
3. Grasp the blue plastic safety tab and pull away from the syringe, and discard. Remove needle cover. Unlike liquid injections, there is no need to remove air bubbles as attempts to do so may displace the ZOLADEX implant.
4. Holding the syringe around the protective sleeve, using an aseptic technique, pinch the skin of the patient’s anterior abdominal wall below the navel line. With the bevel of the needle facing up, insert the needle at a 30 to 45 degree angle to the skin in one continuous deliberate motion until the protective sleeve touches the patient’s skin.
NOTE: The ZOLADEX syringe cannot be used for aspiration. If the hypodermic needle penetrates a large vessel, blood will be seen instantly in the syringe chamber. If a vessel is penetrated, withdraw the needle and inject with a new syringe elsewhere.
5. Do not penetrate into muscle or peritoneum.
6. To administer the ZOLADEX implant and to activate the protective sleeve, grasp the barrel at the finger grip and depress the plunger until you cannot depress it any further. If the plunger is not depressed fully, the protective sleeve will NOT activate. When the protective sleeve ‘clicks’, the protective sleeve will automatically begin to slide to cover the needle.
NOTE: The needle does not retract.
7. Withdraw the needle and allow protective sleeve to slide and cover needle. Dispose of the syringe in an approved sharps collector.
NOTE: In the unlikely event of the need to surgically remove ZOLADEX, it may be localized by ultrasound.
Dosage Forms and StrengthsZOLADEX 10.8 mg implant is supplied as a sterile and totally biodegradable D,L-lactic and glycolic acids copolymer (12.82-14.76 mg/dose) impregnated with goserelin acetate equivalent to 10.8 mg of goserelin in a disposable syringe device fitted with a 14-gauge x 36 +/- 0.5 mm hypodermic siliconized needle with protective needle sleeve [SafeSystem™ Syringe] (NDC 0310-0951-30).
Contraindications HypersensitivityAnaphylactic reactions to ZOLADEX have been reported in the medical literature. ZOLADEX is contraindicated in those patients who have a known hypersensitivity to GnRH, GnRH agonist analogues or any of the components in ZOLADEX [see Warnings and Precautions (5.2) and Adverse Reactions (6.5)].
PregnancyExpected hormonal changes that occur with ZOLADEX treatment increase the risk for pregnancy loss. ZOLADEX may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
Warnings and Precautions Tumor Flare PhenomenonInitially, ZOLADEX, like other GnRH agonists, causes transient increases in serum levels of testosterone. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostatic cancer, may occasionally develop during the first few weeks of ZOLADEX treatment. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other GnRH agonists, isolated cases of ureteral obstruction and spinal cord compression have been observed. If spinal cord compression or renal impairment secondary to ureteral obstruction develops, standard treatment of these complications should be instituted, and in extreme cases an immediate orchiectomy [see Adverse Reactions (6.1) and Patient Counseling Information (17.1)].
HypersensitivityHypersensitivity, antibody formation and acute anaphylactic reactions have been reported with GnRH agonist analogues [see Contraindications (4.1) and Adverse Reactions (6.5)].
Of 115 women worldwide treated with ZOLADEX and tested for development of binding to goserelin following treatment with ZOLADEX, one patient showed low-titer binding to goserelin. On further testing of this patient's plasma obtained following treatment, her goserelin binding component was found not to be precipitated with rabbit antihuman immunoglobulin polyvalent sera. These findings suggest the possibility of antibody formation.
Hyperglycemia and DiabetesHyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes [see Adverse Reactions (6.5) and Patient Counseling Information (17.1)].
Cardiovascular DiseasesIncreased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice [see Patient Counseling Information (17.1)].
Adverse Reactions Clinical TrialsZOLADEX has been found to be generally well tolerated in clinical trials. Adverse reactions reported in these trials were rarely severe enough to result in the patients' withdrawal from ZOLADEX treatment. As seen with other hormonal therapies, the most commonly observed adverse events during ZOLADEX therapy were due to the expected physiological effects from decreased testosterone levels. These included hot flashes, sexual dysfunction and decreased erections.
Tumor Flare Phenomenon: Initially, ZOLADEX, like other GnRH agonists, causes transient increases in serum levels of testosterone. A small percentage of patients experienced a temporary worsening of signs and symptoms, usually manifested by an increase in cancer-related pain which was managed symptomatically. Isolated cases of exacerbation of disease symptoms, either ureteral obstruction or spinal cord compression, occurred at similar rates in controlled clinical trials with both ZOLADEX and orchiectomy. The relationship of these events to therapy is uncertain [see Warnings and Precautions (5.1) and Patient Counseling Information (17.1)].
Stage B2-C Prostatic CarcinomaTreatment with ZOLADEX and flutamide did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing ZOLADEX + flutamide + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below:
Table 1 ADVERSE EVENTS DURING ACUTE RADIATION THERAPY (within first 90 days of radiation therapy) (n=231) (n = 235) flutamide + ZOLADEX + Radiation Radiation Only % All % AllRectum/Large Bowel
80
76
Bladder
58
60
Skin
37
37
Table 2 ADVERSE EVENTS DURING LATE RADIATION PHASE (after 90 days of radiation therapy) (n=231) (n = 235) flutamide + ZOLADEX + Radiation Radiation Only % All % AllDiarrhea
36
40
Cystitis
16
16
Rectal Bleeding
14
20
Proctitis
8
8
Hematuria
7
12
Additional adverse event data was collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study. Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%).
Prostatic CarcinomaTwo controlled clinical trials using ZOLADEX 10.8 mg versus ZOLADEX 3.6 mg were conducted. During a comparative phase, patients were randomized to receive either a single 10.8 mg implant or three consecutive 3.6 mg implants every 4 weeks over weeks 0-12. During this phase, the only adverse event reported in greater than 5% of patients was hot flashes, with an incidence of 47% in the ZOLADEX 10.8 mg group and 48% in the ZOLADEX 3.6 mg group.
From weeks 12-48 all patients were treated with a 10.8 mg implant every 12 weeks. During this noncomparative phase, the following adverse events were reported in greater than 5% of patients:
Table 3 Adverse Events were reported in greater than 5% of Patients Adverse Event ZOLADEX 10.8 mg(n=157)
%
Hot Flashes
64
Pain (general)
14
Gynecomastia
8
Pelvic Pain
6
Bone Pain
6
Asthenia
5
The following adverse events were reported in greater than 1%, but less than 5% of patients treated with ZOLADEX 10.8 mg implant every 12 weeks. Some of these are commonly reported in elderly patients.
WHOLE BODY – Abdominal pain, Back pain, Flu syndrome, Headache, Sepsis, Aggravation reaction
CARDIOVASCULAR – Angina pectoris, Cerebral ischemia, Cerebrovascular accident, Heart failure, Pulmonary embolus, Varicose veins
DIGESTIVE – Diarrhea, Hematemesis
ENDOCRINE – Diabetes mellitus
HEMATOLOGIC – Anemia
METABOLIC –Peripheral edema
NERVOUS SYSTEM – Dizziness, Paresthesia, Urinary retention
RESPIRATORY – Cough increased, Dyspnea, Pneumonia
SKIN – Herpes simplex, Pruritus
UROGENITAL – Bladder neoplasm, Breast pain, Hematuria, Impotence, Urinary frequency, Urinary incontinence, Urinary tract disorder, Urinary tract infection, Urination impaired
The following adverse events not already listed above were reported in patients receiving ZOLADEX 3.6 mg in other clinical trials. Inclusion does not necessarily represent a causal relationship to ZOLADEX 10.8 mg.
WHOLE BODY: Allergic reaction, Chills, Fever, Infection, Injection site reaction, Lethargy, Malaise
CARDIOVASCULAR: Arrhythmia, Chest pain, Hemorrhage, Hypertension, Migraine, Myocardial infarction, Palpitations, Peripheral vascular disorder, Tachycardia
DIGESTIVE: Anorexia, Constipation, Dry mouth, Dyspepsia, Flatulence, Increased appetite, Nausea, Ulcer, Vomiting
HEMATOLOGIC: Ecchymosis
METABOLIC: Edema, Gout, Hyperglycemia, Weight increase
MUSCULOSKELETAL: Arthralgia, Hypertonia, Joint disorder, Leg cramps, Myalgia, Osteoporosis
NERVOUS SYSTEM: Anxiety, Depression, Emotional lability, Headache, Insomnia, Nervousness, Somnolence, Thinking abnormal
RESPIRATORY: Bronchitis, Chronic obstructive pulmonary disease, Epistaxis, Rhinitis, Sinusitis, Upper respiratory infection, Voice alterations
SKIN: Acne, Alopecia, Dry skin, Hair disorders, Rash, Seborrhea, Skin discoloration, Sweating
SPECIAL SENSES: Amblyopia, Dry eyes
UROGENITAL: Breast tenderness, Decreased erections, Renal insufficiency, Sexual dysfunction, Urinary obstruction
Changes in Laboratory Values During TreatmentPlasma Enzymes: Elevation of liver enzymes (AST, ALT) have been reported in female patients exposed to ZOLADEX 3.6 mg (representing less than 1% of all patients). There was no other evidence of abnormal liver function. Causality between these changes and ZOLADEX have not been established.
Lipids: In a controlled trial in females, ZOLADEX 3.6 mg implant therapy resulted in a minor, but statistically significant effect on serum lipids (i.e., increases in LDL cholesterol of 21.3 mg/dL; increases in HDL cholesterol of 2.7 mg/dL; and triglycerides increased by 8.0 mg/dL).
Post-MarketingHypersensitivity: Rarely, hypersensitivity reactions (including urticaria and anaphylaxis) have been reported in patients receiving ZOLADEX [see Contraindications (4.1) and Warnings and Precautions (5.2)].
Hypercalcemia: As with other endocrine therapies, hypercalcemia (increased calcium) has rarely been reported in cancer patients with bone metastases following initiation of treatment with ZOLADEX or other GnRH agonists.
Bone Mineral Density: There have been post-marketing reports of osteoporosis, decreased bone mineral density and bony fracture in men treated with ZOLADEX for prostate cancer [see Patient Counseling Information (17.1)].
Changes in Blood Pressure: Changes in blood pressure, manifest as hypotension or hypertension, have been occasionally observed in patients administered ZOLADEX. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with ZOLADEX. Rarely, such changes have been sufficient to require medical intervention including withdrawal of treatment from ZOLADEX.
Pituitary Apoplexy and Tumors: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed. Most of the pituitary apoplexy cases occurred within 2 weeks of the first dose, and some occurred within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required. Very rare cases of pituitary tumors have been reported.
Glucose Tolerance: Reduction in glucose tolerance, manifesting as diabetes or loss of glycemic control in those with pre-existing diabetes, has been reported during treatment with GnRH agonists, including ZOLADEX [see Warnings and Precautions (5.3) and Patient Counseling Information (17.1)].
Other Adverse Reactions: Psychotic disorders have also been reported.
Drug InteractionsNo formal drug-drug interaction studies have been performed.
No drug interaction studies with other drugs have been conducted with ZOLADEX. No confirmed interactions have been reported between ZOLADEX and other drugs.
Drug/Laboratory Test InteractionsAdministration of ZOLADEX in therapeutic doses results in suppression of the pituitary-gonadal system. Because of this suppression, diagnostic tests of pituitary-gonadotropic and gonadal functions conducted during treatment may show results which are misleading.
USE IN SPECIFIC POPULATIONS PregnancyPregnancy Category X
Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies, ZOLADEX may cause fetal harm when administered to a pregnant woman. Expected hormone changes that occur with ZOLADEX treatment increase the risk for pregnancy loss. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Contraindications (4.2)].
ZOLADEX crosses the placenta in rats and rabbits following subcutaneous administration. Administration of goserelin to pregnant rats and rabbits during organogenesis resulted in increased preimplantation loss and increased resorptions. When pregnant rats received goserelin throughout gestation and lactation, there was a dose-related increase in umbilical hernia in offspring. In additional reproduction studies in rats, goserelin decreased fetus and pup survival. Human dose/exposure multiples could not be calculated from available animal data.
Actual animal doses: rat (? 2 mcg/kg/day for pregnancy loss; ? 10 mcg/kg/day for umbilical hernia in offspring); rabbits (> 20 mcg/kg/day).
Nursing MothersIt is not known if goserelin is excreted in human milk. Goserelin is excreted in the milk of lactating rats. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ZOLADEX, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric UseSafety and effectiveness in pediatric patients have not been established.
Geriatric UseThere is no need for any dosage adjustment when administering ZOLADEX 10.8 mg to geriatric patients.
Renal InsufficiencyIn clinical trials with the solution formulation of goserelin, subjects with impaired renal function (creatinine clearance < 20 mL/min) had a serum elimination half-life of 12.1 hours compared to 4.2 hours for subjects with normal renal function (creatinine clearance > 70 mL/min). However, there was no evidence for any accumulation of goserelin on multiple dosing of the ZOLADEX 10.8 mg depot to subjects with impaired renal function. There was no evidence for any increase in incidence of adverse events in renally impaired patients administered the 10.8 mg depot. These data indicate that there is no need for any dosage adjustment when administering ZOLADEX 10.8 mg to subjects with impaired renal function.
Hepatic InsufficiencyThe total body clearances and serum elimination half-lives were similar between normal subjects and patients with moderate hepatic impairment (alanine transaminase < 3xULN and asparate aminotransferase < 3xULN) when treated with a 250 mcg subcutaneous formulation of goserelin. This pharmacokinetic study indicates that no dose adjustment is needed in patients with moderately impaired liver function. There is no pharmacokinetic data with goserelin in patients with severe hepatic insufficiency.
Body WeightA decline of approximately 1 to 2.5% in the AUC after administration of a 10.8 mg depot was observed with a kilogram increase in body weight. In obese patients who have not responded clinically, testosterone levels should be monitored closely.
OverdosageThe pharmacologic properties of ZOLADEX and its mode of administration make accidental or intentional overdosage unlikely. There is no experience of overdosage from clinical trials. Animal studies indicate that no increased pharmacologic effect occurred at higher doses or more frequent administration. Subcutaneous doses of the drug as high as 1 mg/kg/day in rats and dogs did not produce any nonendocrine related sequelae; this dose is up to 250 times the estimated human daily dose based on the body surface area. If overdosage occurs, it should be managed symptomatically.
Zoladex 3-Month DescriptionZOLADEX® (goserelin acetate implant) is a GnRH agonist. Goserelin acetate is chemically described as an acetate salt of [D-Ser(But)6,Azgly10]. Its chemical structure is pyro-Glu-His-Trp-Ser-Tyr-D-Ser(But)-Leu-Arg-Pro-Azgly-NH2 acetate [C59H84N18O14 ·(C2H4O2)x where x = 1 to 2.4].
Goserelin acetate is an off-white powder with a molecular weight of 1269 Daltons (free base). It is freely soluble in glacial acetic acid. It is soluble in water, 0.1M hydrochloric acid, 0.1M sodium hydroxide, dimethylformamide and dimethyl sulfoxide. Goserelin acetate is practically insoluble in acetone, chloroform and ether.
ZOLADEX 10.8 mg implant is supplied as a sterile, biodegradable product containing goserelin acetate equivalent to 10.8 mg of goserelin. ZOLADEX is designed for subcutaneous implantation with continuous release over a 12-week period. Goserelin acetate is dispersed in a matrix of D,L-lactic and glycolic acids copolymer (12.82–14.76 mg/dose) containing less than 2% acetic acid and up to 10% goserelin-related substances and presented as a sterile, white to cream colored 1.5 mm diameter cylinder, preloaded in a special single-use syringe with a 14-gauge x 36 +/- 0.5 mm siliconized needle with protective needle sleeve (SafeSystem™ Syringe) in a sealed, light- and moisture-proof, aluminum foil laminate pouch containing a desiccant capsule.
Studies of the D,L-lactic and glycolic acids copolymer have indicated that it is completely biodegradable and has no demonstrable antigenic potential.
ZOLADEX is also supplied as a sterile, biodegradable product containing goserelin acetate equivalent to 3.6 mg of goserelin designed for administration every 28 days.
Zoladex 3-Month - Clinical Pharmacology Mechanism of ActionZOLADEX is a synthetic decapeptide analogue of GnRH. ZOLADEX acts as an inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation.
In animal and in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor.
PharmacodynamicsFollowing initial administration, ZOLADEX causes an initial increase in serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone. Chronic administration of ZOLADEX leads to sustained suppression of pituitary gonadotropins, and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 21 days after initiation of therapy. This leads to accessory sex organ regression.
In clinical trials using ZOLADEX 3.6 mg with follow-up of more than 2 years, suppression of serum testosterone to castrate levels has been maintained for the duration of therapy.
PharmacokineticsAbsorption
The pharmacokinetics of ZOLADEX have been determined in healthy male volunteers and patients. In healthy males, radiolabeled goserelin was administered as a single 250 mcg (aqueous solution) dose by the subcutaneous route. The absorption of radiolabeled drug was rapid, and the peak blood radioactivity levels occurred between 0.5 and 1.0 hour after dosing.
The overall pharmacokinetic profile of goserelin following administration of a ZOLADEX 10.8 mg depot to patients with prostate cancer was determined. The initial release of goserelin from the depot was relatively rapid resulting in a peak concentration at 2 hours after dosing. From Day 4 until the end of the 12-week dosing interval, the sustained release of goserelin from the depot produced reasonably stable systemic exposure. Mean (Standard Deviation) pharmacokinetic data are presented in Table 4. There is no clinically significant accumulation of goserelin following administration of four depots administered at 12-week intervals.
Table 4 - Goserelin pharmacokinetic parameters for the 10.8 mg depot Parameter N Mean (SD)Systemic clearance (mL/min)
41
121
(42.4)
Cmax (ng/mL)
41
8.85
(2.83)
Tmax (h)
41
1.80
(0.34)
Cmin (ng/mL)
44
0.37
(0.21)
SD = standard deviation
Serum goserelin concentrations in prostate cancer patients administered three 3.6 mg depots followed by one 10.8 mg depot are displayed in Figure 1. The profiles for both formulations are primarily dependent upon the rate of drug release from the depots. For the 3.6 mg depot, mean concentrations gradually rise to reach a peak of about 3 ng/mL at around 15 days after administration and then decline to approximately 0.5 ng/mL by the end of the treatment period. For the 10.8 mg depot, mean concentrations increase to reach a peak of about 8 ng/mL within the first 24 hours and then decline rapidly up to Day 4. Thereafter, mean concentrations remain relatively stable in the range of about 0.3 to 1 ng/mL up to the end of the treatment period.
Administration of four ZOLADEX 10.8 mg depots to patients with prostate cancer resulted in testosterone levels that were suppressed to and maintained within the range normally observed in surgically castrated men (0 – 1.73 nmol/L or 0-50 ng/dL), over the dosing interval in approximately 91% (145/160) of patients studied. In 6 of 15 patients that escaped from castrate range, serum testosterone levels were maintained below 2.0 nmol/L (58 ng/dL) and in only one of the 15 patients did the depot completely fail to maintain serum testosterone levels to within the castrate range over a 336-day period (4 depot injections). In the 8 additional patients, a transient escape was followed 14 days later by a level within the castrate range.
Distribution
The apparent volume of distribution determined after subcutaneous administration of 250 mcg aqueous solution of goserelin was 44.1 ± 13.6 liters for healthy males. The plasma protein binding of goserelin was found to be 27%.
Metabolism
Metabolism of goserelin, by hydrolysis of the C-terminal amino acids, is the major clearance mechanism. The major circulating component in serum appeared to be 1–7 fragment, and the major component present in urine of one healthy male volunteer was 5-10 fragment. The metabolism of goserelin in humans yields a similar but narrow profile of metabolites to that found in other species. All metabolites found in humans have also been found in toxicology species.
Excretion
Clearance of goserelin following subcutaneous administration of a radiolabeled solution of goserelin was very rapid and occurred via a combination of hepatic and urinary excretion. More than 90% of a subcutaneous radiolabeled solution formulation dose of goserelin was excreted in urine. Approximately 20% of the dose recovered in urine was accounted for by unchanged goserelin.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of FertilitySubcutaneous implantation of goserelin in male and female rats once every 4 weeks for 1 year and recovery for 23 weeks at doses of about 80 and 150 mcg/kg (males) and 50 and 100 mcg/kg (females) daily resulted in an increased incidence of pituitary adenomas. An increased incidence of pituitary adenomas was also observed following subcutaneous implant of goserelin in rats at similar dose levels for a period of 72 weeks in males and 101 weeks in females. The relevance of the rat pituitary adenomas to humans has not been established. Subcutaneous implants of goserelin every 3 weeks for 2 years delivered to mice at doses of up to 2400 mcg/kg/day resulted in an increased incidence of histiocytic sarcoma of the vertebral column and femur. Human dose/exposure multiples could not be calculated from available animal data.
Mutagenicity tests using bacterial and mammalian systems for point mutations and cytogenetic effects have provided no evidence for mutagenic potential.
Administration of goserelin led to changes that were consistent with gonadal suppression in both male and female rats as a result of its endocrine action. In male rats administered 500-1000 mcg/kg/day, a decrease in weight and atrophic histological changes were observed in the testes, epididymis, seminal vesicle and prostate gland with complete suppression of spermatogenesis. In female rats administered 50-1000 mcg/kg/day, suppression of ovarian function led to decreased size and weight of ovaries and secondary sex organs; follicular development was arrested at the antral stage and the corpora lutea were reduced in size and number. Except for the testes, almost complete histologic reversal of these effects in males and females was observed several weeks after dosing was stopped; however, fertility and general reproductive performance were reduced in those that became pregnant after goserelin was discontinued. Fertile matings occurred within 2 weeks after cessation of dosing, even though total recovery of reproductive function may not have occurred before mating took place; and, the ovulation rate, the corresponding implantation rate, and number of live fetuses were reduced.
Based on histological examination, drug effects on reproductive organs were reversible in male and female dogs administered 107-214 mcg/kg/day goserelin when drug treatment was stopped after continuous administration for 1 year. Human dose/exposure multiples could not be calculated from available animal data.
Clinical Studies Stage B2-C Prostatic CarcinomaThe effects of hormonal treatment combined with radiation were studied in 466 patients (231 ZOLADEX + flutamide + radiation, 235 radiation alone) with bulky primary tumors confined to the prostate (stage B2) or extending beyond the capsule (stage C), with or without pelvic node involvement.
In this multicentered, controlled trial, administration of ZOLADEX (3.6 mg depot) and flutamide capsules (250 mg t.i.d.) prior to and during radiation was associated with a significantly lower rate of local failure compared to radiation alone (16% vs 33% at 4 years, P<0.001). The combination therapy also resulted in a trend toward reduction in the incidence of distant metastases (27% vs 36% at 4 years, P =0.058). Median disease-free survival was significantly increased in patients who received complete hormonal therapy combined with radiation as compared to those patients who received radiation alone (4.4 vs 2.6 years, P<0.001). Inclusion of normal PSA level as a criterion for disease-free survival also resulted in significantly increased median disease-free survival in patients receiving the combination therapy (2.7 vs 1.5 years, P<0.001).
Prostatic CarcinomaIn two controlled clinical trials, 160 patients with advanced prostate cancer were randomized to receive either one 3.6 mg ZOLADEX implant every four weeks or a single 10.8 mg ZOLADEX implant every 12 weeks. Mean serum testosterone suppression was similar between the two arms. PSA falls at three months were 94% in patients who received the 10.8 mg implant and 92.5% in patients that received three 3.6 mg implants.
Periodic monitoring of serum testosterone levels should be considered if the anticipated clinical or biochemical response to treatment has not been achieved. A clinical outcome similar to that produced with the use of the 3.6 mg implant administered every 28 days is predicted with ZOLADEX 10.8 mg implant administered every 12 weeks (84 days). Total testosterone was measured by the DPC Coat-A-Count radioimmunoassay method which, as defined by the manufacturers, is highly specific and accurate. Acceptable variability of approximately 20% at low testosterone levels has been demonstrated in the clinical studies performed with the ZOLADEX 10.8 mg depot.
How Supplied/Storage and HandlingZOLADEX 10.8 mg implant is supplied as a sterile and totally biodegradable D,L-lactic and glycolic acids copolymer (12.82-14.76 mg/dose) impregnated with goserelin acetate equivalent to 10.8 mg of goserelin in a disposable syringe device fitted with a 14-gauge x 36 +/- 0.5 mm siliconized hypodermic needle with protective sleeve [SafeSystem™ Syringe] (NDC 0310-0951-30). The unit is sterile and comes in a sealed, light- and moisture-proof, aluminum foil laminate pouch containing a desiccant capsule. Store at room temperature (do not exceed 25°C [77°F]).
Patient Counseling Information MalesThe use of ZOLADEX in patients at particular risk of developing ureteral obstruction or spinal cord compression should be considered carefully and the patients monitored closely during the first month of therapy. Patients with ureteral obstruction or spinal cord compression should have appropriate treatment prior to initiation of ZOLADEX therapy [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
The use of GnRH agonists may cause a reduction in bone mineral density. In men, data suggest the use of a bisphosphonate in combination with a GnRH agonist may reduce bone mineral loss [see Adverse Reactions (6.5)].
Patients should be informed that diabetes, or loss of glycemic control in patients with pre-existing diabetes, has been reported during treatment with GnRH agonists, including ZOLADEX. Therefore, consideration should be given to monitoring blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving ZOLADEX [see Warnings and Precautions (5.3) and Adverse Reactions (6.5)].
A small increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice [see Warnings and Precautions (5.4) ].
ZOLADEX is a trademark of the AstraZeneca group of companies.
©AstraZeneca 2010
Distributed by:
AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
Rev. 12/10
PACKAGE LABEL.PRINCIPAL DISPLAY PANELZOLADEX
goserelin acetate implant Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0310-0951 Route of Administration SUBCUTANEOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength GOSERELIN ACETATE (GOSERELIN) GOSERELIN 10.8 mg Inactive Ingredients Ingredient Name Strength GLYCOLIC ACID LACTIC ACID, DL- Product Characteristics Color Score Shape Size Flavor Imprint Code Contains Packaging # NDC Package Description Multilevel Packaging 1 0310-0951-30 1 POUCH In 1 CARTON contains a POUCH 1 1 SYRINGE In 1 POUCH This package is contained within the CARTON (0310-0951-30) and contains a SYRINGE 1 1 IMPLANT In 1 SYRINGE This package is contained within a POUCH and a CARTON (0310-0951-30)
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020578 05/05/2003
Labeler - AstraZeneca Pharmaceuticals LP (054743190) Registrant - AstraZeneca PLC (230790719) Establishment Name Address ID/FEI Operations AstraZeneca UK Limited 232784079 MANUFACTURE Establishment Name Address ID/FEI Operations Bachem AG 482220311 API MANUFACTURE Revised: 12/2010AstraZeneca Pharmaceuticals LP
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