Nytol Caplet

Generic Name: diphenhydramine (DYE fen HYE dra meen) Brand Names: Aler-Tab, Allergy, Allermax, Altaryl, Benadryl Allergy, Benadryl DF, Benadryl Dye Free Allergy, Benadryl Ultratab, Children's Allergy, Diphen Cough, Diphenhist, Dytuss, PediaCare Children's Allergy, Q-Dryl, Q-Dryl A/F, Siladryl, Siladryl Allergy, Silphen Cough, Simply Sleep, Sleep-ettes, Sleep-ettes D, Sominex Maximum Strength Caplet, Theraflu Thin Strips Multi Symptom, Triaminic Thin Strips Cough & Runny Nose, Unisom Sleepgels Maximum Strength, Valu-Dryl

What is Nytol Caplet (diphenhydramine)?

Diphenhydramine is an antihistamine. Diphenhydramine blocks the effects of the naturally occurring chemical histamine in the body.

Diphenhydramine is used to treat sneezing; runny nose; itching, watery eyes; hives; rashes; itching; and other symptoms of allergies and the common cold.

Diphenhydramine is also used to suppress coughs, to treat motion sickness, to induce sleep, and to treat mild forms of Parkinson's disease.

Diphenhydramine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Nytol Caplet (diphenhydramine)? Use caution when driving, operating machinery, or performing other hazardous activities. Diphenhydramine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking diphenhydramine. What should I discuss with my healthcare provider before taking Nytol Caplet (diphenhydramine)? Do not take diphenhydramine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A very dangerous drug interaction could occur, leading to serious side effects.

Before taking this medication, tell your doctor if you have

glaucoma or increased pressure in the eye;

a stomach ulcer;

an enlarged prostate, bladder problems or difficulty urinating;

an overactive thyroid (hyperthyroidism);

hypertension or any type of heart problems; or

asthma.

You may not be able to take diphenhydramine, or you may require a lower dose or special monitoring during treatment if you have any of the conditions listed above.

Diphenhydramine is in the FDA pregnancy category B. This means that it is not expected to be harmful to an unborn baby. Do not take diphenhydramine without first talking to your doctor if you are pregnant. Infants are especially sensitive to the effects of antihistamines, and side effects could occur in a breast-feeding baby. Do not take diphenhydramine without first talking to your doctor if you are nursing a baby. If you are over 60 years of age, you may be more likely to experience side effects from diphenhydramine. You may require a lower dose of this medication. How should I take Nytol Caplet (diphenhydramine)?

Take diphenhydramine exactly as directed on the package or as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water.

Diphenhydramine can be taken with or without food.

For motion sickness, a dose is usually taken 30 minutes before motion, then with meals and at bedtime for the duration of exposure.

As a sleep aid, diphenhydramine should be taken approximately 30 minutes before bedtime.

To ensure that you get a correct dose, measure the liquid forms of diphenhydramine with a special dose-measuring spoon or cup, not with a regular tablespoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

Never take more of this medication than is prescribed for you. The maximum amount of diphenhydramine that you should take in any 24-hour period is 300 mg.

Store diphenhydramine at room temperature away from moisture and heat. What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.

What happens if I overdose? Seek emergency medical attention if an overdose is suspected.

Symptoms of a diphenhydramine overdose include extreme sleepiness, confusion, weakness, ringing in the ears, blurred vision, large pupils, dry mouth, flushing, fever, shaking, insomnia, hallucinations, and possibly seizures.

What should I avoid while taking Nytol Caplet (diphenhydramine)? Use caution when driving, operating machinery, or performing other hazardous activities. Diphenhydramine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking diphenhydramine. Nytol Caplet (diphenhydramine) side effects Stop taking diphenhydramine and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Other, less serious side effects may be more likely to occur. Continue to take diphenhydramine and talk to your doctor if you experience

sleepiness, fatigue, or dizziness;

headache;

dry mouth; or

difficulty urinating or an enlarged prostate.

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 Nytol Caplet (diphenhydramine)? Do not take diphenhydramine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A very dangerous drug interaction could occur, leading to serious side effects.

Talk to your pharmacist before taking other over-the-counter cough, cold, allergy, or insomnia medications. These products may contain medicines similar to diphenhydramine, which could lead to an antihistamine overdose.

Before taking this medication, tell your doctor if you are taking any of the following medicines:

anxiety or sleep medicines such as alprazolam (Xanax), diazepam (Valium), chlordiazepoxide (Librium), temazepam (Restoril), or triazolam (Halcion);

medications for depression such as amitriptyline (Elavil), doxepin (Sinequan), nortriptyline (Pamelor), fluoxetine (Prozac), sertraline (Zoloft), or paroxetine (Paxil); or

any other medications that make you feel drowsy, sleepy, or relaxed.

Drugs other than those listed here may also interact with diphenhydramine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

More Nytol Caplet resources Nytol Caplet Side Effects (in more detail)Nytol Caplet Use in Pregnancy & BreastfeedingNytol Caplet Drug InteractionsNytol Caplet Support Group0 Reviews for Nytol Caplet - Add your own review/rating Compare Nytol Caplet with other medications Insomnia Where can I get more information? Your pharmacist can provide more information about diphenhydramine.

See also: Nytol Caplet side effects (in more detail)

Nimodipine
Pronunciation: nye-MOE-di-peenGeneric Name: NimodipineBrand Name: Generic only. No brands available.

naproxen

na-PROX-en

Oral route(Tablet;Tablet, Enteric Coated;Suspension)

NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may be increased in patients with cardiovascular disease or risk factors for cardiovascular disease. Naproxen is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. NSAIDs can also cause an increased risk of serious gastrointestinal adverse events especially in the elderly, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal .

Commonly used brand name(s)

In the U.S.

Aflaxen Aleve Aleve Arthritis Anaprox Anaprox DS EC Naprosyn Naprelan Naprelan 500 Naprelan Dose Card Naprosyn

In Canada

Naxen

Available Dosage Forms:

Tablet Suspension Tablet, Enteric Coated Tablet, Extended Release

Therapeutic Class: Analgesic

Pharmacologic Class: NSAID

Chemical Class: Propionic Acid (class)

Uses For naproxen

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis (osteoarthritis, rheumatoid arthritis, or juvenile arthritis) such as inflammation, swelling, stiffness, and joint pain. Naproxen also helps relieve symptoms of ankylosing spondylitis, which is a type of arthritis that affects the joints in the spine. However, naproxen does not cure arthritis and will help you only as long as you continue to take it.

naproxen may also be used to treat mild to moderate pain, including acute gout and other painful conditions such as bursitis, tendonitis, or menstrual cramps.

naproxen is available only with your doctor's prescription.

Before Using naproxen

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For naproxen, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to naproxen or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of naproxen controlled-release tablets in the pediatric population. Safety and efficacy have not been established.

Appropriate studies have not been performed on the relationship of age to the effects of naproxen delayed release tablets, suspension, and tablets in children younger than 2 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of naproxen in the elderly. However, elderly patients may be more sensitive to the effects of naproxen than younger adults, and are more likely to have age-related kidney or stomach problems, which may require caution and an adjustment in the dose for patients receiving naproxen.

Pregnancy Pregnancy Category Explanation All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking naproxen, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using naproxen with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Ketorolac Pentoxifylline

Using naproxen with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abciximab Ardeparin Argatroban Aspirin Beclamide Beta Glucan Bivalirudin Caramiphen Carbamazepine Certoparin Chlormethiazole Cilostazol Citalopram Clopidogrel Clovoxamine Dabigatran Etexilate Dalteparin Danaparoid Desirudin Diazepam Dipyridamole Enoxaparin Escitalopram Ethotoin Felbamate Femoxetine Flesinoxan Fluoxetine Fluvoxamine Fondaparinux Fosphenytoin Gabapentin Ginkgo Heparin Lacosamide Lepirudin Mephenytoin Mephobarbital Methotrexate Nadroparin Nefazodone Oxcarbazepine Paraldehyde Paramethadione Parnaparin Paroxetine Pemetrexed Phenacemide Phenobarbital Phenytoin Piracetam Pregabalin Protein C Reviparin Rivaroxaban Rufinamide Sertraline Sibutramine Stiripentol Tacrolimus Tiagabine Ticlopidine Tinzaparin Tirofiban Topiramate Trimethadione Valproic Acid Vigabatrin Vilazodone Warfarin Zimeldine Zonisamide

Using naproxen with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Acebutolol Acetohexamide Alacepril Alprenolol Amiloride Arotinolol Atenolol Azilsartan Medoxomil Azosemide Befunolol Bemetizide Benazepril Bendroflumethiazide Benzthiazide Betaxolol Bevantolol Bisoprolol Bopindolol Bucindolol Bumetanide Bupranolol Buthiazide Candesartan Cilexetil Canrenoate Captopril Carteolol Carvedilol Celiprolol Chlorothiazide Chlorpropamide Chlorthalidone Cilazapril Clopamide Cyclopenthiazide Cyclosporine Delapril Desvenlafaxine Dilevalol Duloxetine Enalaprilat Enalapril Maleate Eprosartan Esmolol Ethacrynic Acid Fosinopril Furosemide Gliclazide Glimepiride Glipizide Gliquidone Glyburide Hydrochlorothiazide Hydroflumethiazide Imidapril Indapamide Irbesartan Labetalol Landiolol Levobetaxolol Levobunolol Lisinopril Lithium Losartan Mepindolol Methyclothiazide Metipranolol Metolazone Metoprolol Milnacipran Moexipril Nadolol Nebivolol Nipradilol Olmesartan Medoxomil Oxprenolol Penbutolol Pentopril Perindopril Pindolol Piretanide Polythiazide Propranolol Quinapril Ramipril Sotalol Spirapril Spironolactone Talinolol Tasosartan Telmisartan Temocapril Tertatolol Timolol Tolazamide Tolbutamide Torsemide Trandolapril Triamterene Trichlormethiazide Valsartan Venlafaxine Xipamide Zofenopril Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of naproxen. Make sure you tell your doctor if you have any other medical problems, especially:

Anemia or Bleeding problems or Blood clots or Edema (fluid retention or body swelling) or Heart attack, history of or Heart disease (e.g., congestive heart failure) or Hypertension (high blood pressure) or Kidney disease or Liver disease (e.g., hepatitis) or Stomach or intestinal ulcers or bleeding, history of or Stroke, history of—Use with caution. May make these conditions worse. Aspirin-sensitive asthma or Aspirin sensitivity, history of—Should not be used in patients with these conditions. Heart surgery (e.g., coronary artery bypass graft [CABG])—Should not be used to relieve pain right before or after the surgery. Proper Use of naproxen

For safe and effective use of naproxen, do not take more of it, do not take it more often, and do not take it for a longer time than ordered by your doctor. Taking too much of naproxen may increase the chance of unwanted effects, especially in elderly patients.

naproxen should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

When used for severe or continuing arthritis, naproxen must be taken regularly as ordered by your doctor in order for it to help you. naproxen usually begins to work within one week, but in severe cases up to two weeks or even longer may pass before you begin to feel better. Also, several weeks may pass before you feel the full effects of naproxen.

Check with your doctor first before changing dosage forms (e.g., tablets, suspension). These forms are very different from each other.

Swallow the delayed-release tablet whole. Do not crush, break, or chew it.

If you are using the suspension, shake it gently before using it. Use the marked measuring cup included in the package to measure the dose.

Dosing

The dose of naproxen will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of naproxen. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For naproxen (e.g., Naprosyn®) tablet and oral suspension dosage forms: For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: Adults—At first, 250 milligrams (mg) (10 milliliters (mL)/2 teaspoonfuls), 375 mg (15 mL/3 teaspoonfuls), or 500 mg (20 mL/4 teaspoonfuls) two times a day, in the morning and evening. Your doctor may increase your dose, as needed, up to a total of 1500 mg per day. Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 5 milligrams (mg) per kilogram (kg) of body weight two times a day. Children younger than 2 years of age—Use and dose must be determined by your doctor. For bursitis, tendonitis, menstrual cramps, and other kinds of pain: Adults—500 milligrams (mg) for the first dose, then 250 mg every 6 to 8 hours as needed. Children—Use and dose must be determined by your doctor. For acute gout: Adults—750 milligrams (mg) for the first dose, then 250 mg every 8 hours until the attack is relieved. Children—Use and dose must be determined by your doctor. For naproxen controlled-release tablet (e.g., Naprelan®) dosage form: For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: Adults—At first, 750 milligrams (mg) (taken as one 750 mg or two 375 mg tablets) or 1000 mg (taken as two 500 mg tablets) once a day. Your doctor may adjust your dose as needed, up to a total of 1500 mg (taken as two 750 mg or three 500 mg tablets) per day. Children—Use and dose must be determined by your doctor. For bursitis, tendonitis, menstrual cramps, and other kinds of pain: Adults—At first, 1000 milligrams (mg) (taken as two 500 mg tablets) once a day. Some patients may need 1500 mg (taken as two 750 mg or three 500 mg tablets) per day, for a limited period. However, the dose is usually not more than 1000 mg per day. Children—Use and dose must be determined by your doctor. For acute gout: Adults—1000 to 1500 milligrams (mg) (taken as two to three 500 mg tablets) once a day for the first dose, then 1000 mg (taken as two 500 mg tablets) once a day until the attack is relieved. Children—Use and dose must be determined by your doctor. For naproxen delayed-release tablet (e.g., EC-Naprosyn®) dosage form: For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: Adults—At first, 375 or 500 milligrams (mg) two times a day, in the morning and evening. Your doctor may increase the dose, if necessary, up to a total of 1500 mg per day. Children—Use and dose must be determined by your doctor. For naproxen sodium (e.g., Anaprox®, Anaprox® DS) tablet dosage form: For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: Adults—At first, 275 or 550 milligrams (mg) two times a day, in the morning and evening. Your doctor may increase the dose, if necessary, up to a total of 1500 mg per day. Children—Use and dose must be determined by your doctor. For bursitis, tendonitis, menstrual cramps, and other kinds of pain: Adults—550 milligrams (mg) for the first dose, then 550 mg every 12 hours or 275 mg every 6 to 8 hours as needed. Your doctor may increase the dose, if necessary, up to a total of 1375 mg per day. Children—Use and dose must be determined by your doctor. For acute gout: Adults—825 milligrams (mg) for the first dose, then 275 mg every 8 hours until the attack is relieved. Children—Use and dose must be determined by your doctor. Missed Dose

If you miss a dose of naproxen, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using naproxen

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

naproxen may raise your risk of having a heart attack or stroke. This is more likely in people who already have heart disease. People who use naproxen for a long time might also have a higher risk.

naproxen may cause bleeding in your stomach or intestines. This problem can happen without warning signs. This is more likely if you have had a stomach ulcer in the past, if you smoke or drink alcohol regularly, if you are over 60 years of age, are in poor health, or are using certain other medicines (such as a steroid or a blood thinner).

Serious skin reactions can occur during treatment with naproxen. Check with your doctor right away if you have any of the following symptoms while taking naproxen: blistering, peeling, or loosening of the skin; chills; cough; diarrhea; fever; itching; joint or muscle pain; red skin lesions; sore throat; sores, ulcers, or white spots in the mouth or on the lips; or unusual tiredness or weakness.

Possible warning signs of some serious side effects that can occur during treatment with naproxen may include swelling of the face, fingers, feet, or lower legs; severe stomach pain, black, tarry stools, or vomiting of blood or material that looks like coffee grounds; unusual weight gain; yellow skin or eyes; decreased urination; unusual bleeding or bruising; or skin rash. Also, signs of serious heart problems could occur such as chest pain, tightness in the chest, fast or irregular heartbeat, unusual flushing or warmth of the skin, weakness, or slurring of speech. Stop taking naproxen and check with your doctor immediately if you notice any of these warning signs.

naproxen may also cause a serious type of allergic reaction called anaphylaxis. Although this is rare, it may occur more often in patients who are allergic to aspirin or to any of the nonsteroidal anti-inflammatory drugs. Anaphylaxis can be life-threatening and requires immediate medical attention. The most serious signs of this reaction are very fast or irregular breathing, gasping for breath, wheezing, or fainting. Other signs may include changes in color of the skin of the face; very fast but irregular heartbeat or pulse; hive-like swellings on the skin; and puffiness or swellings of the eyelids or around the eyes. If these effects occur, get emergency help at once.

Using naproxen during late pregnancy can harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Check with your doctor immediately if blurred vision, difficulty with reading, or any other change in vision occurs during or after your treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Before having any kind of surgery or medical tests, tell your doctor that you are taking naproxen. It may be necessary for you to stop treatment for a while, or to change to a different nonsteroidal anti-inflammatory drug before your procedure.

naproxen may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to naproxen before you drive, use machines, or do anything else that could be dangerous if you are not alert. .

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

naproxen Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common Belching bruising difficult or labored breathing feeling of indigestion headache itching skin large, flat, blue, or purplish patches in the skin pain in the chest below the breastbone shortness of breath skin eruptions stomach pain swelling tightness in the chest wheezing Less common Bloating bloody or black, tarry stools blurred or loss of vision burning upper abdominal or stomach pain cloudy urine constipation decrease in urine output or decrease in urine-concentrating ability disturbed color perception double vision fast, irregular, pounding, or racing heartbeat or pulse halos around lights indigestion loss of appetite nausea or vomiting night blindness overbright appearance of lights pale skin pinpoint red or purple spots on the skin severe and continuing nausea severe stomach burning, cramping, or pain skin rash swelling or inflammation of the mouth troubled breathing with exertion tunnel vision unusual bleeding or bruising unusual tiredness or weakness vomiting of material that looks like coffee grounds weight loss Rare Anxiety back or leg pains bleeding gums blindness blistering, peeling, or loosening of the skin blood in the urine or stools blue lips and fingernails canker sores change in the ability to see colors, especially blue or yellow chest pain or discomfort clay-colored stools cold sweats coma confusion cool, pale skin cough or hoarseness coughing that sometimes produces a pink frothy sputum cracks in the skin darkened urine decreased vision depression diarrhea difficult, burning, or painful urination difficult, fast, or noisy breathing difficulty with swallowing dilated neck veins dizziness dry cough dry mouth early appearance of redness, or swelling of the skin excess air or gas in the stomach extreme fatigue eye pain fainting fever with or without chills fluid-filled skin blisters flushed, dry skin frequent urination fruit-like breath odor greatly decreased frequency of urination or amount of urine hair loss high fever hives increased hunger increased sensitivity of the skin to sunlight increased sweating increased thirst increased urination increased volume of pale, dilute urine irregular breathing joint or muscle pain large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs late appearance of rash with or without weeping blisters that become crusted, especially in sun-exposed areas of skin, may extend to unexposed areas light-colored stools lightheadedness loss of heat from the body lower back or side pain nervousness nightmares no blood pressure no breathing no pulse nosebleeds numbness or tingling in the hands, feet, or lips pain in the ankles or knees pain or burning in the throat pain or discomfort in the arms, jaw, back, or neck painful, red lumps under the skin, mostly on the legs pains in the stomach, side, or abdomen, possibly radiating to the back pale or blue lips, fingernails, or skin pounding in the ears puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue rapid, shallow breathing red, irritated eyes red skin lesions, often with a purple center red-green color blindness redness or other discoloration of the skin redness, swelling, or soreness of the tongue scaly skin seizures severe sunburn shakiness skin thinness slurred speech sneezing sore throat sores, ulcers, or white spots on the lips or tongue or inside the mouth sores, welting, or blisters spots on your skin resembling a blister or pimple stiff neck or back stomach cramps or tenderness stomach upset swelling in the legs and ankles swelling of the face, fingers, feet, or lower legs swollen, painful, or tender lymph glands in the neck, armpit, or groin tiny bumps on the inner lining of the eyelid unexplained weight loss unpleasant breath odor watery or bloody diarrhea weakness or heaviness of the legs weight gain yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose Bleeding under the skin confusion about identity, place, and time muscle tremors restlessness sleepiness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common Continuing ringing or buzzing or other unexplained noise in the ears hearing loss Less common Acid or sour stomach change in hearing feeling of constant movement of self or surroundings passing gas sensation of spinning stomach soreness or discomfort Rare Appetite changes burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings burning, dry, or itching eyes difficulty with moving discharge, excessive tearing general feeling of discomfort or illness lack or loss of strength menstrual changes muscle aching, cramping, stiffness, or weakness not able to concentrate redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid seeing, hearing, or feeling things that are not there shakiness in the legs, arms, hands, or feet sleeplessness swollen joints trembling or shaking of the hands or feet trouble getting pregnant trouble performing routine tasks trouble sleeping unable to sleep unusual drowsiness, dullness, or feeling of sluggishness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: naproxen side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More naproxen resources Naproxen Side Effects (in more detail)Naproxen Use in Pregnancy & BreastfeedingDrug ImagesNaproxen Drug InteractionsNaproxen Support Group131 Reviews for Naproxen - Add your own review/rating Naproxen Professional Patient Advice (Wolters Kluwer) Naproxen Prescribing Information (FDA) Naproxen Monograph (AHFS DI) Naproxen MedFacts Consumer Leaflet (Wolters Kluwer) Aleve Consumer Overview Anaprox MedFacts Consumer Leaflet (Wolters Kluwer) EC-Naprosyn Enteric-Coated Tablets MedFacts Consumer Leaflet (Wolters Kluwer) Naprosyn Consumer Overview Naprosyn Prescribing Information (FDA) Compare naproxen with other medications Ankylosing SpondylitisAseptic NecrosisBack PainBursitisCostochondritisDiffuse Idiopathic Skeletal HyperostosisDysautonomiaFeverFrozen ShoulderGout, AcuteHeadacheJuvenile Rheumatoid ArthritisMuscle PainOsteoarthritisPainPeriod PainRheumatoid ArthritisSciaticaSpondylolisthesisTendonitis

Nivemycin Tablets 500mg
1. Name Of The Medicinal Product

Nivemycin Tablets 500mg

2. Qualitative And Quantitative Composition

Neomycin sulphate Ph Eur.

an amount equivalent to 550mg of material having a potency of 700 units per mg

3. Pharmaceutical Form

Tablets

4. Clinical Particulars 4.1 Therapeutic Indications

Nivemycin (Neomycin sulphate BP) is indicated for pre-operative sterilisation of the bowel and may be useful in the treatment of impending hepatic coma, including portal systemic encephalopathy.

For oral administration.

4.2 Posology And Method Of Administration

Pre-operative sterilisation of the bowel.

Adults: 2 tablets every hour for 4 hours; then 2 tablets every 4 hours for two or three days before the operation.

Children over 12 years: 2 tablets every 4 hours for 2 or 3 days before the operation.

Children from 6 to 12 years: ? to 1 tablet every 4 hours for 2 or 3 days before the operation.

For practical reasons, use of the tablets in children under 6 years is not recommended.

In hepatic coma, the adult dose is 4-12 gm/day in divided doses for a period of 5-7 days, whilst for children, 50-100mg/kg/day in divided doses appears appropriate. Chronic hepatic insufficiency may require up to 4 gm/day over an indefinite period.

The elderly dose is the same as for adults.

4.3 Contraindications

Nivemycin should not be given when intestinal obstruction is present.

Hypersensitivity to aminoglycosides.

Infants under 1 year.

Myasthenia gravis

4.4 Special Warnings And Precautions For Use

The absorption of neomycin is poor from the alimentary tract, with about 97% of an orally administered dose being excreted unchanged in the faeces. Impaired G.I. motility however may increase absorption of the drug and it is therefore possible, as with other broad spectrum antibiotics, that prolonged therapy could result in ototoxicity and nephrotoxicity, particularly in patients with a degree of renal failure. In such patients, and in infants and the elderly, it is generally desirable to determine dosage requirements of aminoglycosides by individual monitoring. Some authorities consider that monitoring is also important in obese patients and those with cystic fibrosis.

Impaired hepatic function or auditory function, bacteraemia, fever, and possibly exposure to loud noises have been reported to increase the risk of ototoxicity, while volume depletion or hypotension, liver disease, or female sex have been reported as additional risk factors for nephrotoxicity. Regular assessment of auditory, vestibular and renal function is particularly necessary in patients with additional risk factors.

When used as an adjunct in the management of hepatic coma, care should be taken that administration is of the minimal period necessary, since prolonged exposure to the drug may result in malabsorption.

Neomycin should be used with caution in patients with neuromuscular disorders and parkinsonism.

There is almost complete cross-resistance between neomycin, kanamycin, paromomycin and framycetin. Cross-resistance with gentamicin has also been reported.

Since prolonged therapy may result in the overgrowth of non-sensitive organisms, treatment should not be continued longer than necessary to prevent superinfection due to the overgrowth of non-sensitive organisms.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Neomycin may impair absorption of other drugs including phenoxymethylpenicillin,digoxin, methotrexate and some vitamins. Aminoglycosides exhibit synergistic activity with a number of beta lactams, but aminoglycoside activity was reported to be diminished in a few patients with severe renal impairment.

Care should be taken when considering the use of neomycin concurrently with drugs with a potential to cause nephrotoxicity (including other aminoglycosides, some of the cephalosporins, amphotericin, ciclosporin, capreomycin, polymyxins, platinum compounds, teicoplanin and vancomycin) or ototoxicity (including, loop diuretics, capreomycin, teicoplanin, vancomycin and possibly platinum coumpounds).

The effect of non-depolarising muscle relaxants may be enhanced by aminoglycosides.

Care is required if other drugs with a neuromuscular blocking action, including botulinum toxin, are given concomitantly. Care is required when patients being treated with aminoglycosides are to receive a general anaesthetic or opioids in order to avoid the possible neuromuscular side-effects provoking severe respiratory depression.

The effect of the parasympathomimetic drugs neostigmine and pyridostigmine, may be antagonised by aminoglycosides.

The hypoglycaemic effect of acarbose may be enhanced by neomycin and the severity of gastrointestinal side effects increased.

Aminoglycosides may increase the risk of hypocalcaemia in patients receiving bisphosphonates.

Experience in anticoagulant clinics suggests that INR (International Normalised Ratio) may be altered by antibacterials such as neomycin given for local action on the gut, although studies have failed to demonstrate an interaction with phenindione.

The efficacy of oral contraceptives may be reduced with broad spectrum antibiotics.

Oral typhoid vaccine is inactivated by concomitant antibiotic administration.

4.6 Pregnancy And Lactation

The use of neomycin in pregnancy is not recommended unless the benefits outweigh the potential risks.

There are no reports linking the use of neomycin to congenital defects. However, small amounts of the drug are absorbed when given orally and neomycin and other aminoglycosides may have harmful effects on the foetus following oral absorption during pregnancy.

In some circumstances neomycin may enter the breast milk of lactating mothers. There is little risk of ototoxicity in the infant, but abnormal development of the gut flora may occur. The use of neomycin in lactating mothers is not recommended unless the benefits outweigh the potential risks.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

Nausea, vomiting, diarrhoea, increased salivation, stomatitis, nephrotoxicity, ototoxicity, rise in serum levels of hepatic enzymes and bilirubin, blood dyscrasias, haemolytic anaemia, confusion, paraesthesia, disorientation, nystagmus, hypersensitivity reactionsincluding dermatitis, pruritus, drug fever and anaphylaxis.

Cross-sensitivity with other aminoglycosides may occur.

Malabsorption syndrome with steatorrhoea and diarrhoea, which can be severe, may be caused by prolonged oral therapy.

Superinfection may occur, especially with prolonged oral treatment.

Electrolyte disturbances (notably hypomagnesaemia but also hypocalcaemia and hypokalaemia) have occurred with other aminoglycosides.

4.9 Overdose

In overdose, exacerbation of the adverse events reported for neomycin (nausea, diarrhoea, nephrotoxicity, ototoxicity etc.) is expected.

Monitor renal and auditory function. If these are impaired, haemodialysis is indicated. Prolonged assisted ventilation may also be required.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Neomycin is an aminoglycoside antibiotic.

Neomycin acts by binding to polysomes, inhibiting protein synthesis and generating errors in the transcription of the genetic code.

5.2 Pharmacokinetic Properties

The absorption of neomycin from the alimentary tract is poor: Only ~ 3% of an oral dose is absorbed, neomycin is rapidly excreted by the kidneys in the unchanged form. The plasma half-life in healthy adults is approximately 2-3 hours. Oral doses of 3 g produce peak plasma concentrations of up to 4 ?g/ml.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Plasdone K29-32

Isopropyl alcohol

Calcium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Store below 30°C in a dry place – protect from light.

6.5 Nature And Contents Of Container

An amber glass bottle having a tin-plate screw cap with a waxed aluminium-faced pulpboard liner. The ullage is filled with cotton wool.

Pack size: 100 tablets.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data 7. Marketing Authorisation Holder

Waymade Plc.

Trading as Sovereign Medical

Sovereign House

Miles Gray Road

Basildon

Essex SS14 3FR

8. Marketing Authorisation Number(S)

PL 06464/0710

9. Date Of First Authorisation/Renewal Of The Authorisation

11 January 1999

10. Date Of Revision Of The Text

July 2003

Novolog Mix 70/30
Dosage Form: injection, suspensionFULL PRESCRIBING INFORMATION Indications and Usage for Novolog Mix 70/30

Novolog Mix 70/30 is an insulin analog indicated to improve glycemic control in patients with diabetes mellitus.

 Important Limitations of Use:

 In premix insulins, such as Novolog Mix 70/30, the proportions of rapid acting and long acting insulins are fixed and do not allow for basal versus prandial dose adjustments.

Novolog Mix 70/30 Dosage and Administration Dosing

Novolog Mix 70/30 is an insulin analog with an earlier onset and intermediate duration of action in comparison to the basal human insulin premix. The addition of protamine to the rapid-acting aspart insulin analog (NovoLog) results in insulin activity that is 30% short-acting and 70% long-acting. Novolog Mix 70/30 is typically dosed on a twice-daily basis (with each dose intended to cover 2 meals or a meal and a snack). The dosage of Novolog Mix 70/30 must be individualized. The written prescription for Novolog Mix 70/30 should include the full name, to avoid confusion with NovoLog (insulin aspart) and Novolin 70/30 (human premix).

Novolog Mix 70/30 should appear uniformly white and cloudy. Do not use it if it looks clear or if it contains solid particles. Novolog Mix 70/30 should not be used after the printed expiration date.

Novolog Mix 70/30 should be administered by subcutaneous injection in the abdominal region,  buttocks, thigh, or upper arm. Novolog Mix 70/30 has a faster onset of action than human insulin premix 70/30 and should be dosed within 15 minutes before meal initiation for patients with type 1 diabetes. For patients with type 2 diabetes, dosing should occur within 15 minutes before or after meal initiation. Injection sites should be rotated within the same region to reduce the risk of lipodystrophy. As with all insulins, the duration of action may vary according to the dose, injection site, blood flow, temperature, and level of physical activity.

Novolog Mix 70/30 should not be administered intravenously or used in insulin infusion pumps. Dose regimens of Novolog Mix 70/30 will vary among patients and should be determined by the health care professional familiar with the patient’s recommended glucose treatment goals, metabolic needs, eating habits, and other lifestyle variables.

Resuspension

Novolog Mix 70/30 is a suspension that must be visually inspected and resuspended immediately before use. The Novolog Mix 70/30 vial should be rolled gently in your hands in a horizontal position 10 times to mix it. The rolling procedure must be repeated until the suspension appears uniformly white and cloudy. Inject immediately. Resuspension is easier when the insulin has reached room temperature.

The Novolog Mix 70/30 FlexPen should be rolled 10 times gently between your hands in a horizontal position. Thereafter, turn the Novolog Mix 70/30 FlexPen upside down so that the glass ball moves from one end of the reservoir to the other. Do this at least 10 times. The rolling and turning procedure must be repeated until the suspension appears uniformly white and cloudy. Inject immediately. Before each subsequent injection, turn the disposable Novolog Mix 70/30 FlexPen upside down so that the glass ball moves from one end of the reservoir to the other at least 10 times and until the suspension appears uniformly white and cloudy. Inject immediately.

Dosage Forms and Strengths

Novolog Mix 70/30 is available in the following package sizes: each presentation contains 100 units of insulin aspart per mL (U-100).

10 mL vials 3 mL Novolog Mix 70/30 FlexPen Contraindications

Novolog Mix 70/30 is contraindicated

during episodes of hypoglycemia in patients with hypersensitivity to NovoLog  Mix 70/30 or one of its excipients. Warnings and Precautions Administration

The short and long-acting components of insulin mixes, including Novolog Mix 70/30, cannot be titrated independently. Because Novolog Mix 70/30 has peak pharmacodynamic activity between 1-4 hours after injection, it should be administered within 15 minutes of meal initiation [see Clinical Pharmacology (12)]. The dose of insulin required to provide adequate glycemic control for one of the meals may result in hyper- or hypoglycemia for the other meal. The pharmacodynamic profile may also be inadequate for patients who require more frequent meals.

Novolog Mix 70/30 should not be mixed with any other insulin product.

Novolog Mix 70/30 should not be used intravenously.

Novolog Mix 70/30 should not be used in insulin infusion pumps.

Glucose monitoring is recommended for all patients with diabetes. Any change of insulin dose should be made cautiously and only under medical supervision. Changing from one insulin product to another or changing the insulin strength may result in the need for a change in dosage. Changes may also be necessary during illness, emotional stress, and other physiologic stress in addition to changes in meals and exercise.

The pharmacokinetic and pharmacodynamic profiles of all insulins may be altered by the site used for injection and the degree of vascularization of the site. Smoking, temperature, and exercise contribute to variations in blood flow and insulin absorption. These and other factors contribute to inter- and intra-patient variability.

Needles and Novolog Mix 70/30 FlexPen must not be shared.

Hypoglycemia

Hypoglycemia is the most common adverse effect of insulin therapy, including Novolog Mix 70/30. Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. Severe hypoglycemia requiring the assistance of another person and/or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with Novolog Mix 70/30.

The timing of hypoglycemia may reflect the time-action profile of the insulin formulation [see Clinical Pharmacology (12)]. Other factors, such as changes in dietary intake (e.g., amount of food or timing of meals), injection site, exercise, and concomitant medications may also alter the risk of hypoglycemia [see Drug Interactions (7)]. As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g. patients who are fasting or have erratic food intake). The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating machinery.

Rapid changes in serum glucose levels may induce symptoms of hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as beta-blockers, or intensified diabetes control [see Drug Interactions (7)].

Hypokalemia

All insulin products, including Novolog Mix 70/30, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia that, if left untreated, may cause respiratory paralysis, ventricular arrhythmia, and death. Use caution in patients who may be at risk for hypokalemia (e.g. patients using potassium-lowering medications or patients taking medications sensitive to potassium concentrations).

Renal Impairment

Clinical or pharmacology studies with Novolog Mix 70/30 in diabetic patients with various degrees of renal impairment have not been conducted. As with other insulins, the requirements for Novolog Mix 70/30 may be reduced in patients with renal impairment [see Clinical Pharmacology (12.3)].

Hepatic Impairment

Clinical or pharmacology studies with Novolog Mix 70/30 in diabetic patients with various degrees of hepatic impairment have not been conducted. As with other insulins, the requirements for Novolog Mix 70/30 may be reduced in patients with hepatic impairment [see Clinical Pharmacology (12.3)].

Hypersensitivity and Allergic Reactions

Local Reactions- As with other insulin therapy, patients may experience reactions such as erythema, edema or pruritus at the site of Novolog Mix 70/30 injection. These reactions usually resolve in a few days to a few weeks, but in some occasions, may require  discontinuation of Novolog Mix 70/30. In some instances, these reactions may be related to the insulin molecule, other components in the insulin preparation including protamine and cresol, components in skin cleansing agents, or injection techniques. Localized reactions and generalized myalgias have been reported with the use of cresol as an injectable excipient.

Systemic Reactions- Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life threatening.

Antibody Production

Specific anti-insulin antibodies as well as cross-reacting anti-insulin antibodies were monitored in a 3-month, open-label comparator trial as well as in a long-term extension trial. Changes in cross-reactive antibodies were more common after Novolog Mix 70/30 than with Novolin 70/30 but these changes did not correlate with change in HbA1c or increase in insulin dose. The clinical significance of these antibodies has not been established. Antibodies did not increase further after long-term exposure (>6 months) to Novolog Mix 70/30.

Adverse Reactions

Clinical Trial Experience

Clinical trials are conducted under widely varying designs, therefore, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

Hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Novolog Mix 70/30 [see Warnings and Precautions (5.2)]. Novolog Mix 70/30 should not be used during episodes of hypoglycemia [see Contraindications (4)] and [Warnings and Precautions (5)].

Insulin initiation and glucose control intensification

Intensification or rapid improvement in glucose control has been associated with transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Lipodystrophy

Long-term use of insulin, including Novolog Mix 70/30, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection sites within the same region to reduce the risk of lipodystrophy.

Weight gain

Weight gain can occur with some insulin therapies, including Novolog Mix 70/30, and has been attributed to the anabolic effects of insulin and the decrease in glycosuria.

Peripheral Edema

Insulin may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Frequencies of adverse drug reactions

The frequencies of adverse drug reactions during a clinical trial with Novolog Mix 70/30 in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below. The trial was a three-month, open-label trial in patients with Type 1 or Type 2 diabetes who were treated twice daily (before breakfast and before supper) with Novolog Mix 70/30.

Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 diabetes mellitus (Adverse events with frequency ? 5% are included.)

Novolog Mix 70/30

(N=55)

Novolin 70/30

(N=49) Preferred Term N % N % Hypoglycemia 38 69 37 76 Headache 19 35 6 12 Influenza-like symptoms 7 13 1 2 Dyspepsia 5 9 3 6 Back pain 4 7 2 4 Diarrhea 4 7 3 6 Pharyngitis 4 7 1 2 Rhinitis 3 5 6 12 Skeletal pain 3 5 2 4 Upper respiratory tract infection 3 5 1 2 Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 diabetes mellitus (Adverse events with frequency ? 5% are included.)

Novolog Mix 70/30

(N=85)

Novolin 70/30

(N=102) Preferred Term N % N % Hypoglycemia 40 47 51 50 Upper respiratory tract infection 10 12 6 6 Headache 8 9 8 8 Diarrhea 7 8 2 2 Neuropathy 7 8 2 2 Pharyngitis 5 6 4 4 Abdominal pain 4 5 0 0 Rhinitis 4 5 2 2

Postmarketing Data

Additional adverse reactions have been identified during post-approval use of Novolog Mix 70/30. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency. They include medication errors in which other insulins have been accidentally substituted for Novolog Mix 70/30 [see Patient Counseling Information (17)].

Drug Interactions

A number of substances affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.

The following are examples of substances that may increase the blood-glucose-lowering effect and susceptibility to hypoglycemia: oral antidiabetic products, pramlintide, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene, salicylates, somatostatin analog (e.g. octreotide), sulfonamide antibiotics. The following are examples of substances that may reduce the blood-glucose-lowering effect: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), atypical antipsychotics. Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic products such as beta-blockers, clonidine, guanethidine, and reserpine. USE IN SPECIFIC POPULATIONS Pregnancy

Pregnancy Category B.

All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential in such patients.

An open-label, randomized study compared the safety and efficacy of NovoLog (the rapid-acting component of Novolog Mix 70/30) versus human insulin in the treatment of pregnant women with Type 1 diabetes (322 exposed pregnancies (NovoLog: 157, human insulin: 165)). Two-thirds of the enrolled patients were already pregnant when they entered the study. Since only one-third of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Mean HbA1c of ~ 6% was observed in both groups during pregnancy, and there was no significant difference in the incidence of maternal hypoglycemia.

Animal reproduction studies have not been conducted with Novolog Mix 70/30. However, subcutaneous reproduction and teratology studies have been performed with NovoLog (the rapid-acting component of Novolog Mix 70/30) and regular human insulin in rats and rabbits. In these studies, NovoLog was given to female rats before mating, during mating, and throughout pregnancy, and to rabbits during organogenesis. The effects of NovoLog did not differ from those observed with subcutaneous regular human insulin.

NovoLog, like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 U/kg/day (approximately 32-times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area), and in rabbits at a dose of 10 U/kg/day (approximately three times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area). The effects are probably secondary to maternal hypoglycemia at high doses. No significant effects were observed in rats at a dose of 50 U/kg/day and rabbits at a dose of 3 U/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1.0 U/kg/day for rats and equal to the human subcutaneous dose of 1.0 U/kg/day for rabbits based on U/body surface area.

Female patients should be advised to discuss with their physician if they intend to, or if they become pregnant. There are no adequate and well-controlled studies of the use of Novolog Mix 70/30 in pregnant women.

Nursing Mothers

It is unknown whether insulin aspart is excreted in human milk as occurs with human insulin. There are no adequate and well-controlled studies of the use of Novolog Mix 70/30 or NovoLog in lactating women. Women with diabetes who are lactating may require adjustments of their insulin doses. 

Pediatric Use

Safety and effectiveness of Novolog Mix 70/30 have not been established in pediatric patients.

Geriatric Use

Clinical studies of Novolog Mix 70/30 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.

Overdosage

Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery.

Novolog Mix 70/30 Description

Novolog Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection, [rDNA origin]) is a human insulin analog suspension containing 70% insulin aspart protamine crystals and 30% soluble insulin aspart. Novolog Mix 70/30 is a blood-glucose-lowering agent with an earlier onset and an intermediate duration of action. Insulin aspart is homologous with regular human insulin with the exception of a single substitution of the amino acid proline by aspartic acid in position B28, and is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker’s yeast). Insulin aspart (NovoLog) has the empirical formula C256H381N65O79S6 and a molecular weight of 5825.8 Da.

Figure 1. Structural formula of insulin aspart

Novolog Mix 70/30 is a uniform, white, sterile suspension that contains insulin aspart 100 Units/mL.

Inactive ingredients are glycerol 16.0 mg/mL, phenol 1.50 mg/mL, metacresol 1.72 mg/mL, zinc 19.6 ?g/mL, disodium hydrogen phosphate dihydrate 1.25 mg/mL, sodium chloride 0.877 mg/mL, and protamine sulfate 0.32 mg/mL. Novolog Mix 70/30 has a pH of 7.20 - 7.44. Hydrochloric acid or sodium hydroxide may be added to adjust pH.

Novolog Mix 70/30 - Clinical Pharmacology Mechanism of Action

The primary activity of Novolog Mix 70/30 is the regulation of glucose metabolism. Insulins, including Novolog Mix 70/30, bind to the insulin receptors on muscle, liver and fat cells and lower blood glucose by facilitating the cellular uptake of glucose and simultaneously inhibiting the output of glucose from the liver.

Pharmacodynamics

The two euglycemic clamp studies described below [see Clinical Pharmacology (12.3)] assessed glucose utilization after dosing of healthy volunteers. Novolog Mix 70/30 has an earlier onset of action than human premix 70/30 in studies of normal volunteers and patients with diabetes. The onset of action is between 10-20 minutes for Novolog Mix 70/30 compared to 30 minutes for Novolin 70/30. The mean ± SD time to peak activity for Novolog Mix 70/30 is 2.4 hr ± 0.8 hr compared to 4.2 hr ± 0.4 hr for Novolin 70/30. The duration of action may be as long as 24 hours (see Figure 2).

Figure 2. Pharmacodynamic Activity Profile of Novolog Mix 70/30 and Novolin 70/30 in healthy subjects.

Pharmacokinetics

The single substitution of the amino acid proline with aspartic acid at position B28 in insulin aspart (NovoLog) reduces the molecule’s tendency to form hexamers as observed with regular human insulin. The rapid absorption characteristics of NovoLog are maintained by Novolog Mix 70/30. The insulin aspart in the soluble component of Novolog Mix 70/30 is absorbed more rapidly from the subcutaneous layer than regular human insulin. The remaining 70% is in crystalline form as insulin aspart protamine which has a prolonged absorption profile after subcutaneous injection.

Bioavailability and Absorption- The relative bioavailability of Novolog Mix 70/30 compared to NovoLog and Novolin 70/30 indicates that the insulins are absorbed to similar extent. In euglycemic clamp studies in healthy volunteers (n=23) after dosing with Novolog Mix 70/30 (0.2 U/kg), a mean maximum serum concentration (Cmax) of 23.4 ± 5.3 mU/L was reached after 60 minutes. The mean half-life (t1/2) of Novolog Mix 70/30 was about 8 to 9 hours. Serum insulin levels returned to baseline 15 to 18 hours after a subcutaneous dose of Novolog Mix 70/30. Similar data were seen in a separate euglycemic clamp study in healthy volunteers (n=24) after dosing with Novolog Mix 70/30 (0.3 U/kg). A Cmax of 61.3 ± 20.1 mU/L was reached after 85 minutes. Serum insulin levels returned to baseline 12 hours after a subcutaneous dose.

The Cmax and the area under the insulin concentration-time curve (AUC) after administration of Novolog Mix 70/30 was approximately 20% greater than those after administration of Novolin 70/30, (see Fig. 3 for pharmacokinetic profiles).

Figure 3. Pharmacokinetic Profiles of NovoLog  Mix 70/30 and Novolin 70/30

Distribution and Elimination- NovoLog has a low binding to plasma proteins, 0 to 9%, similar to regular human insulin. After subcutaneous administration in normal male volunteers (n=24), NovoLog was more rapidly eliminated than regular human insulin with an average apparent half-life of 81 minutes compared to 141 minutes for regular human insulin.

The effect of sex, age, obesity, ethnic origin, renal and hepatic impairment, pregnancy, or smoking, on the pharmacodynamics and pharmacokinetics of Novolog Mix 70/30 has not been studied.

Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility

Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of Novolog Mix 70/30. In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with NovoLog, the rapid-acting component of Novolog Mix 70/30, at 10, 50, and 200 U/kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area, respectively). At a dose of 200 U/kg/day, NovoLog increased the incidence of mammary gland tumors in females when compared to untreated controls. The incidence of mammary tumors found with NovoLog was not significantly different from that found with regular human insulin. The relevance of these findings to humans is not known.

NovoLog was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and in ex vivo UDS test in rat liver hepatocytes.

In fertility studies in male and female rats, NovoLog at subcutaneous doses up to 200 U/kg/day (approximately 32 times the human subcutaneous dose, based on U/body surface area) had no direct adverse effects on male and female fertility, or on general reproductive performance of animals.

Animal Toxicology and/or Pharmacology

In standard biological assays in mice and rabbits, one unit of NovoLog has the same glucose-lowering effect as one unit of regular human insulin. However, the effect of Novolog Mix 70/30 is more rapid in onset compared to Novolin (human insulin) 70/30 due to its faster absorption after subcutaneous injection.

Clinical Studies Novolog Mix 70/30 versus Novolin 70/30

In a three-month, open-label trial, patients with Type 1 (n=104) or Type 2 (n=187) diabetes were treated twice daily (before breakfast and before supper) with Novolog Mix 70/30 or Novolin 70/30. Patients had received insulin for at least 24 months before the study. Oral hypoglycemic agents were not allowed within 1 month prior to the study or during the study. The small changes in HbA1c were comparable across the treatment groups (see Table 3).

Table 3: Glycemic Parameters at the End of Treatment [Mean ± SD (N subjects)] Novolog Mix 70/30 Novolin 70/30 Type 1, N=104 Fasting Blood Glucose (mg/dL) 174 ± 64 (48) 142 ± 59 (44) 1.5 Hour Post Breakfast (mg/dL) 187 ± 82 (48) 200 ± 82 (42) 1.5 Hour Post Dinner (mg/dL) 162 ± 77 (47) 171 ± 66 (41) HbA1c (%) Baseline 8.4 ± 1.2 (51) 8.5 ± 1.1 (46) HbA1c (%) Week 12 8.4 ± 1.1 (51) 8.3 ± 1.0 (47) Type 2, N=187 Fasting Blood Glucose (mg/dL) 153 ± 40 (76) 152 ± 69 (93) 1.5 Hour Post Breakfast (mg/dL) 182 ± 65 (75) 200 ± 80 (92) 1.5 Hour Post Dinner (mg/dL) 168 ± 51 (75) 191 ± 65 (93) HbA1c (%) Baseline 8.1 ± 1.2 (82) 8.2 ± 1.3 (98) HbA1c (%) Week 12 7.9 ± 1.0 (81) 8.1 ± 1.1 (96)

The significance, with respect to the long-term clinical sequelae of diabetes, of the differences in postprandial hyperglycemia between treatment groups has not been established.

Specific anti-insulin antibodies as well as cross-reacting anti-insulin antibodies were monitored in the 3-month, open-label comparator trial as well as in a long-term extension trial.

Combination Therapy: Insulin and Oral Agents in Patients with Type 2 Diabetes

Trial 1:

In a 34-week, open-label trial, insulin-na?ve patients with type 2 diabetes currently treated with 2 oral antidiabetic agents were switched to treatment with metformin and pioglitazone. During an 8-week optimization period metformin and pioglitazone were increased to 2500 mg per day and 30 or 45 mg per day, respectively. After the optimization period, subjects were randomized to receive either Novolog Mix 70/30 twice daily added on to the metformin and pioglitazone regimen or continue the current optimized metformin and pioglitazone therapy. Novolog Mix 70/30 was started at a dose of 6 IU twice daily (before breakfast and before supper). Insulin doses were titrated to a pre-meal glucose goal of 80-110 mg/dL. The total daily insulin dose at the end of the study was 56.9 ± 30.5 IU.

Table 4: Combination Therapy with Oral Agents and Insulin in Patients with Type 2 Diabetes Mellitus [Mean (SD)] Treatment duration 24-weeks

Novolog Mix 70/30 + Metformin

+ Pioglitazone Metformin + Pioglitazone HbA1c Baseline mean ± SD (n) 8.1 ± 1.0 (102) 8.1 ± 1.0 (98) End-of-study mean ± SD (n) - LOCF 6.6 ± 1.0 (93) 7.8 ± 1.2 (87) Adjusted Mean change from baseline ± SE (n)* -1.6 ± 0.1 (93) -0.3 ± 0.1 (87) Treatment difference mean ± SE* 95% CI*

-1.3 ± 0.1

(-1.6, -1.0)

Percentage of subjects reaching HbA1c <7.0% 76% 24% Percentage of subjects reaching HbA1c ?6.5% 59% 12% Fasting Blood Glucose (mg/dL) Baseline Mean ± SD (n) 173 ± 39.8 (93) 163 ± 35.4 (88) End of Study Mean ± SD (n) - LOCF 130 ± 50.0 (90) 162 ± 40.8 (84) Adjusted Mean change from baseline ± SE (n)* -43.0 ± 5.3 (90) -3.9 ± 5.3 (84) End-of-Study Blood Glucose (Plasma) (mg/dL) 2 Hour Post Breakfast 138 ± 42.8 (86) 188 ± 57.7 (74) 2 Hour Post Lunch 150 ± 41.5 (86) 176 ± 56.5 (74) 2 Hour Post Dinner 141 ± 57.8 (86) 195 ± 60.1 (74) % of patients with severe hypoglycemia** 3 0 % of patients with minor hypoglycemia** 52 3 Weight gain at end of study (kg)** 4.6 ± 4.3 (92) 0.8 ± 3.2 (86)

 *Adjusted mean per group, treatment difference, and 95% CI were obtained based on an ANCOVA model with treatment, FPG stratum, and secretagogue stratum as fixed factors and baseline HbA1c as the covariate.

**If metabolic control is improved by intensified insulin therapy, an increased risk of hypoglycemia and weight gain may occur.

 

Trial 2:

In a 28-week, open-label trial, insulin-na?ve patients with type 2 diabetes with fasting plasma glucose above 140 mg/dL currently treated with metformin ± thiazolidinedione therapy were randomized to receive either Novolog Mix 70/30 twice daily [before breakfast and before supper] or insulin glargine once daily1 (see Table 5). Novolog Mix 70/30 was started at an average dose of 5-6 IU (0.07 ± 0.03 IU/kg) twice daily (before breakfast and before supper), and bedtime insulin glargine was started at 10-12 IU (0.13 ± 0.03 IU/kg). Insulin doses were titrated weekly by decrements or increments of -2 to +6 units per injection to a pre-meal glucose goal of 80-110 mg/dL. The metformin dose was adjusted to 2550 mg/day. Approximately one-third of the patients in each group were also treated with pioglitazone (30 mg/day). Insulin secretagogues were discontinued in order to reduce the risk of hypoglycemia. Most patients were Caucasian (53%), and the mean initial weight was 90 kg.

Table 5: Combination Therapy with Oral Agents and Two Types of Insulin in Patients with Type 2 Diabetes Mellitus [Mean (SD)] Treatment duration 28-weeks NovoLog  Mix 70/30 + Metformin ± Pioglitazone Insulin Glargine + Metformin ± Pioglitazone Number of patients 117 116 HbA1c Baseline mean (%) 9.7 ± 1.5 (117) 9.8 ± 1.4 (114) End-of-study mean (± SD) 6.9 ± 1.2 (108) 7.4 ± 1.2 (114) Mean change from baseline -2.7 ± 1.6 (108) -2.4 ± 1.5 (114) Percentage of subjects reaching HbA1c <7.0% 66% 40% Total Daily Insulin Dose at end of study (U) 78 ± 40 (117) 51 ± 27 (116) % of patients with severe hypoglycemia 0 0

Naratriptan
Pronunciation: NAR-a-TRIP-tanGeneric Name: NaratriptanBrand Name: Amerge

Normacol
1. Name Of The Medicinal Product

NORMACOL.

2. Qualitative And Quantitative Composition

The active ingredient is Sterculia 62% w/w.

3. Pharmaceutical Form

Oral granules.

4. Clinical Particulars 4.1 Therapeutic Indications

The treatment of constipation, particularly simple or idiopathic constipation and constipation during pregnancy.

Management of colostomies and ileostomies.

The 'High Residue Diet' management of diverticular disease of the colon and other conditions requiring a high fibre regimen.

The initiation and maintenance of bowel action after rectal and anal surgery.

Administration after ingestion of sharp foreign bodies to provide a coating and reduce the possibility of intestinal damage during transit.

4.2 Posology And Method Of Administration

Adults: 1 or 2 sachets or 1-2 heaped 5ml spoonfuls, once or twice daily after meals.

Elderly: As adult dose.

Children: (6-12 years): one half the above amount.

The granules should be placed dry on the tongue and without chewing or crushing, swallowed immediately with plenty of water or a cool drink. Prior to drinking they may also be sprinkled onto and taken with soft food such as yoghurt.

4.3 Contraindications

Intestinal obstruction, faecal impaction, and total atony of the colon.

Known hypersensitivity to any of the ingredients

4.4 Special Warnings And Precautions For Use

Caution should be exercised in cases of ulcerative colitis.

Patients with rare hereditary problems of fructose intolerance, glucose –galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Not to be taken immediately before going to bed or in a recumbent position especially in the elderly. Adequate fluid should be maintained.

Not to be taken for more than 4 days if there has been no movement of the bowels.

It is not unusual for stool to appear paler in colour than normal as a result of local contact with sterculia. This does not indicate anything untoward.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None known.

4.6 Pregnancy And Lactation

NORMACOL may be recommended during pregnancy or lactation.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Immune system disorders:

Allergic reactions

Gastrointestinal disorders:

Intestinal/colonic obstruction or impaction, flatulence

Occasionally mild abdominal distension may occur.

Oesophageal obstruction is possible if the product is taken in overdosage or if it is not adequately washed down with fluid.

4.9 Overdose

Intestinal obstruction is possible in overdosage particularly in combination with inadequate fluid intake. Management is as for intestinal obstruction from other causes.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Sterculia acts in the colon by forming a soft bulky stool and inducing a laxative effect.

5.2 Pharmacokinetic Properties

Sterculia is not absorbed or digested in the gastrointestinal tract and its laxative action is normally effective within 12 hours of oral administration.

5.3 Preclinical Safety Data

There is no evidence that Sterculia has a significant systemic toxicity potential.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sodium bicarbonate

Sucrose

Talc

Paraffin wax

Titanium dioxide

Vanillin

6.2 Incompatibilities

None known.

6.3 Shelf Life

Sachet and lined carton: 2 years

6.4 Special Precautions For Storage

Store in a dry place below 25°C.

6.5 Nature And Contents Of Container

Sachet containing 7 g of white granules in boxes of 2, 7, 30 or 60 sachets.

Lined box of 100 g or 500 g of white granules.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Norgine Limited

Norgine House

Widewater Place

Moorhall Road

Harefield

UXBRIDGE

Middlesex UB9 6NS

United Kingdom

8. Marketing Authorisation Number(S)

PL 0322/5010R

9. Date Of First Authorisation/Renewal Of The Authorisation

January 1991

10. Date Of Revision Of The Text

July 2010

NiQuitin 4 mg Mint Lozenges / NiQuitin Pre-Quit 4 mg Mint Lozenges
1. Name Of The Medicinal Product

NiQuitin 4 mg Mint Lozenges.

NiQuitin Pre-Quit 4 mg Mint Lozenges.

2. Qualitative And Quantitative Composition

Each lozenge contains 4 mg nicotine (as nicotine resinate). For excipients see Section 6.1.

3. Pharmaceutical Form

Lozenge.

White, round lozenge with convex surfaces, debossed NL4S on one side.

4. Clinical Particulars 4.1 Therapeutic Indications

NiQuitin Mint Lozenges relieve and/or prevent craving and nicotine withdrawal symptoms associated with tobacco dependence. They are indicated to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them.

NiQuitin Mint Lozenges are indicated in pregnant and lactating women making a quit attempt.

NiQuitin Mint Lozenges should preferably be used in conjunction with a behavioural support programme.

4.2 Posology And Method Of Administration

Directions for use:

NiQuitin 4 mg Mint Lozenges are suitable for smokers who have their first cigarette of the day within 30 minutes of waking up.

One lozenge should be placed in the mouth and allowed to dissolve. Periodically, the lozenge should be moved from one side of the mouth to the other, and repeated, until the lozenge is completely dissolved (approximately 20 – 30 minutes). The lozenge should not be chewed or swallowed whole.

Users should not eat or drink while a lozenge is in the mouth.

Behavioural therapy, advice & support will normally improve the success rate.

Adults (18 years and over):

Abrupt cessation of smoking:

Users should make every effort to stop smoking completely during treatment with NiQuitin Mint Lozenges.

Recommended treatment schedule:

Step 1

Weeks 1 to 6

Step 2

Weeks 7 to 9

Step 3

Weeks 10 to 12

Initial treatment period

Step down treatment period

Step down treatment period

1 lozenge every 1 to 2 hours

1 lozenge every 2 to 4 hours

1 lozenge every 4 to 8 hours

During weeks 1 to 6 it is recommended that users take a minimum of 9 lozenges per day. Users should not exceed 15 lozenges per day.

To help stay smoke free beyond 12 weeks, users may take 1-2 lozenges per day only on occasions when they are strongly tempted to smoke.

Those who have quit smoking but are having difficulty discontinuing using the lozenges are recommended to seek additional help and advice from a healthcare professional.

Gradual cessation of smoking:

For smokers who are unwilling or unable to quit abruptly.

Use a lozenge whenever there is a strong urge to smoke in order to reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible.

The number of lozenges a day is variable and depends on the patients needs. Nonetheless it should not exceed 15 lozenges per day.

If a reduction in cigarette consumption has not been achieved after 6 weeks of treatment, a healthcare professional should be consulted.

Reduced tobacco consumption should lead to complete cessation of smoking. This should be attempted as soon as possible. When the number of cigarettes has been reduced to a level from which the user feels able to quit completely, then start on the schedule for “abrupt cessation” as given above.

If an attempt to stop smoking completely has not been started within 6 months after the beginning of treatment, it is recommended to consult a healthcare professional.

Reduction in smoking:

For smokers who wish to cut down with no immediate plans to quit.

Use a lozenge whenever there is a strong urge to smoke in order to reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible. Users should be encouraged to stop smoking completely as soon as possible.

The number of lozenges a day is variable and depends on the patients needs. Nonetheless it should not exceed 15 lozenges per day.

If users are still feeling the need to use the lozenges on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Temporary abstinence:

Use a lozenge every 1-2 hours to control troublesome withdrawal symptoms including cravings. Users should not take more than 15 lozenges per day.

Users should be encouraged to stop smoking completely as soon as possible.

If users are still feeling the need to use lozenges on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Adolescents and children:

Adolescents (12-17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above. Where adolescents are unwilling or unable to quit smoking abruptly, advice from a healthcare professional should be sought.

Safety and effectiveness in children who smoke has not been evaluated. NiQuitin Mint Lozenges are not recommended for use in children under 12 years of age.

4.3 Contraindications

NiQuitin Mint Lozenges are contraindicated in:

• those with hypersensitivity to nicotine or any of the excipients;

• children under the age of 12 years and non-smokers.

4.4 Special Warnings And Precautions For Use

The risks associated with the use of NRT are substantially outweighed in virtually all circumstances by the well established dangers of continued smoking.

Patients hospitalised for MI, severe dysrhythmia or CVA who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, NiQuitin Mint Lozenges may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision. Once patients are discharged from hospital they can use NRT as normal.

Diabetes Mellitus: Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when NRT is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.

Allergic reactions: Susceptibility to angioedema and urticaria

A risk-benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:

• Renal and hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment and/or severe renal impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

• Phaeochromocytoma and uncontrolled hyperthyroidism: Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.

• GI disease: Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastric or peptic ulcers and oral NRT preparations should be used with caution in these conditions. Ulcerative stomatitis has been reported.

Danger in small children: Doses of nicotine tolerated by adult and adolescent smokers can produce severe toxicity in small children that may be fatal. Products containing nicotine should not be left where they may be misused, handled or ingested by children.

Stopping smoking: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops this may result in a slower metabolism and a consequent rise in blood levels of such drugs.

Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.

Phenylketonuria: NiQuitin Mint Lozenges contain a source of phenylalanine equivalent to 3mg/dose. May be harmful for people with phenylketonuria.

Sodium content: Each NiQuitin Mint Lozenge contains 15 mg of sodium. People on a low sodium diet should take this into account.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically relevant interactions between nicotine replacement therapy and other drugs have definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.

4.6 Pregnancy And Lactation

Pregnancy

Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the foetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but NRT may be used in pregnancy as a safer alternative to smoking. Because of the potential for nicotine-free periods, intermittent dose forms are preferable, but patches may be necessary if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the foetus would not normally be exposed to nicotine.

Lactation

The relatively small amounts of nicotine found in breast milk during NRT use are less hazardous to the infant than second-hand smoke. Intermittent dose forms would minimize the amount of nicotine in breast milk and permit feeding when levels were at their lowest.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

NRT can cause adverse reactions similar to those associated with nicotine administered in other ways, including smoking. These may be attributed to the pharmacological effects of nicotine, some of which are dose dependent. At recommended doses NiQuitin Mint Lozenges have not been found to cause any serious adverse effects. Excessive consumption of NiQuitin Mint Lozenges by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.

Certain symptoms which have been reported such as depression, irritability, anxiety and insomnia may be related to withdrawal symptoms associated with smoking cessation. Subjects quitting smoking by any means could expect to suffer from headache, dizziness, sleep disturbance, increased coughing or a cold.

Related adverse events with excess in active compared to placebo group in a controlled study.

Immune system disorder

   

Very rare <1/10000: anaphylactic reactions

   

Platelet, bleeding and clotting disorders

   

Uncommon >1/1000; <1/100: gingival bleeding

   

Metabolic and nutritional disorders

   

Uncommon >1/1000; <1/100: thirst; excessive thirst

   

Psychiatric disorders

   

Common >1/100; >1/10: insomnia

 

Uncommon >1/1000; <1/100: anxiety; anxiety attack; anxiety reaction; nightmares; marked restlessness; decreased appetite; lost appetite; lethargy

   

Central and peripheral nervous system disorders

   

Common >1/100; <1/10: dizziness; headache

 

Uncommon >1/1000; <1/100; migraine; mucosal burning; burning sensation; paraesthesia mouth; sensory disturbance; hyperalertness

   

Respiratory system disorders

   

Common >1/100; <1/10: coughing; pharyngitis; sore throat

 

Uncommon >1/1000; <1/100: dyspnoea; shortness of breath; aggravated cough; lower respiratory tract infection; respiratory disorder; excessive sneezing

   

Gastrointestinal system disorders

   

Very common >1/10: nausea; hiccup, flatulence

 

Common >1/100; <1/10: vomiting; constipation, diarrheoa; dysphagia; dyspepsia; heartburn; indigestion; belching; mouth irritation, mouth ulceration; tongue ulceration; dry mouth; bloating

 

Uncommon >1/1000; <1/100: gastroesophageal reflux; oesophageal reflux aggravated; retching; eructation; gagging; catarrh; increased saliva; lip ulceration; GI disorder; abdominal griping; sore lips; dry throat

   

Special senses other, disorders:

   

Uncommon >1/1000; <1/100: taste perversion

   

Skin and appendages disorders:

   

Uncommon >1/1000; <1/100: itching; rash

   

Body as a whole: general disorders:

   

Uncommon >1/1000; <1/100: throat swelling; chest pain; tightness of chest; overdose effect; withdrawal syndrome; malaise; hot flushes; halitosis

4.9 Overdose Symptoms: The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 60mg. Symptoms of acute nicotine poisoning include nausea, salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, disturbed hearing and marked weakness. In extreme cases, these symptoms may be followed by hypotension, rapid or weak or irregular pulse, breathing difficulties, prostration, circulatory collapse and terminal convulsions.

Management of an overdose: All nicotine intake should stop immediately and the patient should be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of nicotine.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

ATC Code: N07B A01

Nicotine is an agonist at nicotine receptors in the peripheral and central nervous system and has pronounced CNS and cardiovascular effects. When consumed in tobacco products, it has been shown to be addictive and abstinence is linked to craving and withdrawal symptoms. These craving and withdrawal symptoms include urge to smoke, depressed mood, insomnia, irritability, frustration or anger, anxiety, difficulty in concentrating, restlessness and increased appetite or weight gain. The lozenges replace some of the nicotine provided by tobacco and help reduce the severity of these nicotine craving and withdrawal symptoms.

5.2 Pharmacokinetic Properties

NiQuitin Mint Lozenges dissolve completely in the oral cavity, and the entire amount of nicotine contained in the lozenge becomes available for buccal absorption or ingestion (swallowing). The complete dissolution of NiQuitin Mint Lozenges is typically achieved in 20-30 minutes. The peak plasma concentrations of nicotine achieved after single dose are approximately 10.8 ng/ml. When dosed every 1.5 hours, the steady state peak and trough concentrations are 26.0 and 19.7 ng/ml respectively. Ingestion of NiQuitin Mint Lozenges not following dosing instruction (chewed, retained in the mouth, and swallowed; chewed and immediately swallowed) does not result in faster or higher absorption, but a substantial amount of nicotine (80-93%) is still absorbed.

As the plasma protein binding of nicotine is low (4.9% - 20%), the volume of distribution of nicotine is large (2.5 l/kg). The distribution of nicotine to tissue is pH dependent, with the highest concentrations of nicotine found in the brain, stomach, kidney and liver.

Nicotine is extensively metabolized to a number of metabolites, all of which are less active than the parent compound. The metabolism of nicotine primarily occurs in the liver, but also in the lung and kidney. Nicotine is metabolized primarily to cotinine but is also metabolized to nicotine N?-oxide. Cotinine has a half-life of 15-20 hours and its blood levels are 10 times higher than nicotine. Cotinine is further oxidized to trans-3?-hydroxycotinine, which is the most abundant metabolite of nicotine in the urine. Both nicotine and cotinine undergo glucuronidation.

The elimination half-life of nicotine is approximately 2 hours (range 1 - 4 hours). Total clearance for nicotine ranges from approximately 62 to 89 l/hr. Non-renal clearance for nicotine is estimated to be about 75% of total clearance. Nicotine and its metabolites are excreted almost exclusively in the urine. The renal excretion of unchanged nicotine is highly dependent on urinary pH, with greater excretion occurring at acidic pH.

5.3 Preclinical Safety Data

The general toxicity of nicotine is well known and taken into account in the recommended posology. Nicotine was not mutagenic in appropriate assays. The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine. In studies in pregnant animals, nicotine showed maternal toxicity, and consequential mild fetal toxicity. Additional effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development.

Effects were only noted following exposure to nicotine at levels in excess of those which will result from recommended use of NiQuitin Mint Lozenges. Effects on fertility have not been established.

Comparison of the systemic exposure necessary to elicit these adverse responses from preclinical test systems with that associated with the recommended use of NiQuitin Mint Lozenges indicate that the potential risk is low and outweighed by the demonstrable benefit of nicotine therapy in smoking cessation. However, NiQuitin Mint Lozenges should only be used by pregnant women on medical advice if other forms of treatment have failed.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Mannitol

Sodium alginate

Xanthan gum

Potassium bicarbonate

Calcium polycarbophil

Sodium carbonate anhydrous

Aspartame

Magnesium stearate

Mint flavour powder 57581

6.2 Incompatibilities

None known.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 25°C. Store in the original package.

6.5 Nature And Contents Of Container

Clear or opaque Polyvinyl Chloride/Polyethylene/Polyvinylidene Chloride blisters in packs of 12, 24, 36, 48, 72, 96, 108 and 144, or a polypropylene tablet container with cap containing 24 lozenges in packs of 24, 48 and 72.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Beecham Group plc

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

T/A GlaxoSmithKline Consumer Healthcare

Brentford, TW8 9GS, UK

8. Marketing Authorisation Number(S)

PL 00079/0370

9. Date Of First Authorisation/Renewal Of The Authorisation

24 September 2001

10. Date Of Revision Of The Text

23/03/2011

Norethindrone/Ethinyl Estradiol Chewable Tablets
Pronunciation: nor-ETH-in-drone/ETH-i-nil ES-tra-DYE-ol/FER-us FUE-ma-rateGeneric Name: Norethindrone/Ethinyl EstradiolBrand Name: Femcon Fe

Nutr-E-Sol

Generic Name: vitamin e (Oral route)

VYE-ta-min E

Commonly used brand name(s)

In the U.S.

Alpha-E Aqua Gem-E Aquasol E D-Alpha Gems E-400 E-600 E-Gems Formula E 400 Gamma E-Gems Gamma E Plus Key-E Natural Vitamin Blend E-400IU Nutr-E-Sol

Available Dosage Forms:

Liquid Solution Tablet Capsule, Liquid Filled Tablet, Chewable Powder for Solution Capsule

Therapeutic Class: Nutritive Agent

Pharmacologic Class: Vitamin E (class)

Uses For Nutr-E-Sol

Vitamins are compounds that you must have for growth and health. They are needed in only small amounts and are available in the foods that you eat. Vitamin E prevents a chemical reaction called oxidation, which can sometimes result in harmful effects in your body. It is also important for the proper function of nerves and muscles.

Some conditions may increase your need for vitamin E. These include:

Intestine disease Liver disease Pancreas disease Surgical removal of stomach

Increased need for vitamin E should be determined by your health care professional.

Infants who are receiving a formula that is not fortified with vitamin E may be likely to have a vitamin E deficiency. Also, diets high in polyunsaturated fatty acids may increase your need for vitamin E.

Claims that vitamin E is effective for treatment of cancer and for prevention or treatment of acne, aging, loss of hair, bee stings, liver spots on the hands, bursitis, diaper rash, frostbite, stomach ulcer, heart attacks, labor pains, certain blood diseases, miscarriage, muscular dystrophy, poor posture, sexual impotence, sterility, infertility, menopause, sunburn, and lung damage from air pollution have not been proven. Although vitamin E is being used to prevent certain types of cancer, there is not enough information to show that this is effective.

Lack of vitamin E is extremely rare, except in people who have a disease in which it is not absorbed into the body.

Vitamin E is available without a prescription.

Importance of Diet

For good health, it is important that you eat a balanced and varied diet. Follow carefully any diet program your health care professional may recommend. For your specific dietary vitamin and/or mineral needs, ask your health care professional for a list of appropriate foods. If you think that you are not getting enough vitamins and/or minerals in your diet, you may choose to take a dietary supplement.

Vitamin E is found in various foods including vegetable oils (corn, cottonseed, soybean, safflower), wheat germ, whole-grain cereals, and green leafy vegetables. Cooking and storage may destroy some of the vitamin E in foods.

Vitamin supplements alone will not take the place of a good diet and will not provide energy. Your body also needs other substances found in food such as protein, minerals, carbohydrates, and fat. Vitamins themselves often cannot work without the presence of other foods. For example, small amounts of fat are needed so that vitamin E can be absorbed into the body.

The daily amount of vitamin E needed is defined in several different ways.

For U.S.— Recommended Dietary Allowances (RDAs) are the amount of vitamins and minerals needed to provide for adequate nutrition in most healthy persons. RDAs for a given nutrient may vary depending on a person's age, sex, and physical condition (e.g., pregnancy). Daily Values (DVs) are used on food and dietary supplement labels to indicate the percent of the recommended daily amount of each nutrient that a serving provides. DV replaces the previous designation of United States Recommended Daily Allowances (USRDAs). For Canada— Recommended Nutrient Intakes (RNIs) are used to determine the amounts of vitamins, minerals, and protein needed to provide adequate nutrition and lessen the risk of chronic disease.

Vitamin E is available in various forms, including d- or dl-alpha tocopheryl acetate, d- or dl-alpha tocopherol, and d- or dl-alpha tocopheryl acid succinate. In the past, the RDA for vitamin E have been expressed in Units. This term has been replaced by alpha tocopherol equivalents (alpha-TE) or milligrams (mg) of d-alpha tocopherol. One Unit is equivalent to 1 mg of dl-alpha tocopherol acetate or 0.6 mg d-alpha tocopherol. Most products available in stores continue to be labeled in Units.

Normal daily recommended intakes in milligrams (mg) of alpha tocopherol equivalents (mg alpha-TE) and Units for vitamin E are generally defined as follows:

                                                  Persons U.S. Canada mg alpha-TE Units mg alpha-TE Units   Infants and children

Nuvigil
Pronunciation: ar-moe-DAF-i-nilGeneric Name: ArmodafinilBrand Name: Nuvigil

NexMed, Inc
Address NexMed, Inc, 89 Twin Rivers Drive East Windsor, NJ 08520 Contact DetailsPhone: (609) 371-8123

NTZ Long Acting Nasal

Generic Name: oxymetazoline nasal (ox ee me TAZ oh leen) Brand Names: Afrin, Afrin Nasal Sinus, Allerest 12 Hour Nasal Spray, Duramist Plus, Duration, Four-Way Nasal Spray, Genasal, Neo-Synephrine 12 Hour, Nostrilla, NRS Nasal, NTZ Long Acting Nasal, Oxyfrin, Oxymeta-12, Sinarest Nasal, Sinex Long-Acting, Twice-A-Day

What is NTZ Long Acting Nasal (oxymetazoline nasal)?

Oxymetazoline is a decongestant. It works by constricting (shrinking) blood vessels (veins and arteries) in your body. The nasal formulation acts directly on the blood vessels in your nasal tissues. Constriction of the blood vessels in your nose and sinuses leads to drainage of these areas and a decrease in congestion.

Oxymetazoline nasal is used to treat congestion associated with allergies, hay fever, sinus irritation, and the common cold.

Oxymetazoline nasal may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about NTZ Long Acting Nasal (oxymetazoline nasal)?

Do not use oxymetazoline nasal for longer than 3 to 5 days. Longer use could cause damage to your nasal tissue and lead to chronic congestion. If your symptoms do not improve, see your doctor.

Do not use more of this medication than is recommended on the package or by your doctor. Who should not use NTZ Long Acting Nasal (oxymetazoline nasal)? Do not use oxymetazoline nasal if you have taken a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. This could cause a very dangerous drug interaction with serious side effects.

Before taking this medication, tell your doctor if you have

high blood pressure;

any type of heart disease, hardening of the arteries, or irregular heart beats;

thyroid problems;

diabetes;

glaucoma or increased pressure in the eye;

an enlarged prostate or difficulty urinating; or

liver or kidney disease.

You may not be able to use oxymetazoline nasal, or you may require a lower dose or special monitoring during your therapy if you have any of the conditions listed above.

It is not known whether oxymetazoline nasal will harm an unborn baby. Do not use oxymetazoline nasal without first talking to your doctor if you are pregnant. Infants are especially sensitive to the effects of oxymetazoline nasal. Do not use this medication without first talking to your doctor if you are breast-feeding a baby. If you over 60 years of age, you may be more likely to experience side effects from oxymetazoline nasal. You may require a lower dose of this medication. How should I use NTZ Long Acting Nasal (oxymetazoline nasal)?

Use oxymetazoline nasal exactly as directed by your doctor, or follow the instructions that accompany the package. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

To apply the nasal spray, keep your head upright, spray, then sniff hard for a few minutes after administering a dose.

To apply the nasal drops, lie on a bed on your back with your head hanging over the edge. Insert the drops and remain in this position for several minutes. Gently turn your head from side to side.

Do not allow the tip of the container to touch the inside of your nose or any other surface. This spreads the infection.

Also, to prevent the spread of infection, do not share this medication with anyone else.

Discard this medication bottle after use. Do not save it for reuse.

Never use this medication in larger doses or more often than is recommended. Too much oxymetazoline nasal could be very harmful. Oxymetazoline nasal should not be used more often than twice a day (every 12 hours).

Do not use oxymetazoline nasal for longer than 3 to 5 days. Longer use could cause damage to your nasal tissue and lead to chronic congestion. If your symptoms do not improve, see your doctor.

Store oxymetazoline nasal at room temperature away from moisture and heat.

What happens if I miss a dose?

Use the missed dose as soon as you remember. However, if it is almost time for your next regularly scheduled dose, skip the missed dose and use the next one as directed. Do not use a double dose of this medication.

What happens if I overdose? Seek emergency medical attention.

Symptoms of an oxymetazoline nasal overdose include extreme tiredness, sweating, dizziness, a slow heartbeat, and coma.

What should I avoid while taking NTZ Long Acting Nasal (oxymetazoline nasal)? Never use this medication in larger doses or more often than is recommended. Too much oxymetazoline nasal could be very harmful. NTZ Long Acting Nasal (oxymetazoline nasal) side effects

If you experience any of the following serious side effects, stop using oxymetazoline nasal and seek emergency medical attention:

an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives);

seizures;

unusual behavior or hallucinations; or

an irregular or fast heartbeat.

More commonly, you may experience some sneezing or burning, stinging, dryness, or irritation of the nose. These side effects are usually mild and temporary.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect NTZ Long Acting Nasal (oxymetazoline nasal)? Do not use oxymetazoline nasal if you have taken a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days.

Although drug interactions between topical nasal decongestants and drugs taken by mouth are not expected, they can occur. Rarely, oxymetazoline nasal may interact with the following medicines:

furazolidone (Furoxone);

guanethidine (Ismelin);

indomethacin (Indocin);

methyldopa (Aldomet);

bromocriptine (Parlodel);

caffeine in cola, tea, coffee, chocolate and other products;

theophylline (Theo-Dur, Theochron, Theolair, others);

tricyclic antidepressants such as amitriptyline (Elavil, Endep), doxepin (Sinequan), and nortriptyline (Pamelor); other commonly used tricyclic antidepressants, including amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), imipramine (Tofranil), protriptyline (Vivactil), and trimipramine (Surmontil); phenothiazines such as chlorpromazine (Thorazine), thioridazine (Mellaril), and prochlorperazine (Compazine); and other commonly used phenothiazines, including fluphenazine (Prolixin), perphenazine (Trilafon), mesoridazine (Serentil), and trifluoperazine (Stelazine).

Drugs other than those listed here may also interact with oxymetazoline nasal. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More NTZ Long Acting Nasal resources NTZ Long Acting Nasal Side Effects (in more detail)NTZ Long Acting Nasal Use in Pregnancy & BreastfeedingNTZ Long Acting Nasal Drug InteractionsNTZ Long Acting Nasal Support Group0 Reviews for NTZ Long Acting Nasal - Add your own review/rating Afrin Advanced Consumer (Micromedex) - Includes Dosage Information Afrin Solution MedFacts Consumer Leaflet (Wolters Kluwer) Compare NTZ Long Acting Nasal with other medications Nasal Congestion Where can I get more information? Your pharmacist has additional information about oxymetazoline nasal written for health professionals that you may read.

See also: NTZ Long Acting Nasal side effects (in more detail)

NIOPAM 300
1. Name Of The Medicinal Product

NIOPAM 300 , solution for injection

2. Qualitative And Quantitative Composition

61.2% w/v Iopamidol equivalent to 300mg iodine/ml.

Each ml contains 612 mg iopamidol.

For excipients, see 6.1.

3. Pharmaceutical Form

Solution for injection.

Clear aqueous solution filled into colourless glass ampoules or bottles.

4. Clinical Particulars 4.1 Therapeutic Indications

X-ray contrast medium for use in lumbar and thoraco-cervical myelography, cerebral angiography, peripheral angiography, venography, computer tomography enhancement, urography and arthrography.

4.2 Posology And Method Of Administration

Route of administration:

Intra-ventricular

Intra-arterial

Intra-venous

Intra-articular

Intra-thecal

Intra-cisternal

Dosage

NIOPAM 300 : DOSAGE SCHEDULE

Procedure

Dosage

Lumbar Myelography

Adults 5 - 10 ml

Thoraco-Cervical Myelography

Adults 5 - 10 ml

Cerebral Angiography

Adults 5 - 10 ml *

Children **

Peripheral Arteriography

 

Venography

Adults 20 - 50 ml *

Children **

Adults 20 - 50 ml *

Children **

Do not exceed 250 ml

Computer Tomography Enhancement

Adults: Brain scanning 50 - 100ml

Whole body scanning 40-100ml

Intravenous Urography

Adults 40 - 80 ml

In severe renal failure the usual high dose methods should be employed. (up to 1.5 mg/kg)

Children 1 - 2.5 mg/kg or **

Arthrography

Adults 1 - 10 ml according to the joint being examined.

* repeat as necessary; ** according to body size and age;

Single injection volume depends on the vascular area to be examined.

Elderly: dosage as for adults. The lowest effective dose should be used.

Method of administration

No other drugs should be mixed with the contrast medium.

Lumbar myelography

A slow sub-arachnoid injection is made through a fine lumbar puncture needle into one of the lower lumbar interspinous spaces (L3-L4 or L4-L5). Optimum contrast appears immediately after injections and films should be obtained promptly.

Thoraco-cervical myelography

Following a slow sub-arachnoid injection the patient should be turned on his side and tilted 10°-20° head down under fluoroscopic control. In this manner it is possible to control movement of the contrast medium column into the dorsal region.

If the cervical region is to be examined, the contrast medium should be run into the cervical region first, before the examination of the dorsal areas where it is progressively diluted.

Niopam may also be injected sub-occipitally or by lateral cervical puncture technique. Care should be taken to ensure that the contrast medium does not move intracranially.

Following intrathecal use, the patient should rest with the head and chest elevated for one hour and be kept well hydrated. Thereafter, he/she may ambulate carefully but bending down be avoided. If remaining in bed, the head and chest should be kept elevated for 6 hours. Patients suspected of having a low seizure threshold should be observed during this period.

Cerebral angiography

Any of the current techniques is suitable for radiological visualisation of the cerebral vasculature with Niopam 300. Carotid and vertebral angiography, performed by catheterisation or percutaneous injection techniques, require rapid injection, which, if necessary may be repeated.

Peripheral arteriography and phlebography (venography)

Percutaneous injection into the appropriate blood vessel is used for visualisation of peripheral arteries and veins.

Computer tomography enhancement

Contrast enhancement for brain scans can be achieved between one and three minutes after i.v. injection. Niopam 200, 300 and 340 are also used for total body scanning examinations after i.v. administration as a bolus, as a drip infusion or by a combination of the two methods.

Urography

The contrast medium is injected intravenously and rapidly eliminated through the kidneys. In patients with severe renal failure, high dose urography should be used.

Arthrography

Visualisation of joint cavities and articular surfaces can be achieved by either single or double contrast examination.

4.3 Contraindications

Use in patients with proven or suspected hypersensitivity to iodine containing preparations of this type.

Because of overdosage considerations, immediate repeat myelography in the event of technical failure is contraindicated.

4.4 Special Warnings And Precautions For Use

A positive history of allergy, asthma or untoward reaction during previous similar investigations indicates a need for extra caution; the benefit should clearly outweigh the risk in such patients. Appropriate resuscitative measures should be immediately available.

X-ray examination of women should if possible be conducted during the pre-ovulation phase of the menstrual cycle and should be avoided during pregnancy.

When examining small children or babies, do not limit fluid intake before administering a hypertonic contrast solution. Also, correct any existing water and electrolyte imbalance.

Care should be exercised in carrying out radiographic procedures with contrast media in patients with severe functional impairment of the liver or myocardium, severe systemic disease and in myelomatosis (including Waldenstr?ms macroglobulinemia, multiple myeloma). In the latter condition patients should not be exposed to dehydration; similarly abnormalities of fluid or electrolyte balance should be corrected prior to use.

Particular care should also be exercised in patients with moderate to severe impairment of renal function (as reflected by a raised blood urea) or in diabetes. Substantial deterioration in renal function is minimised if the patient is well hydrated. Renal function parameters should be monitored after the procedure in these patients.

Patients with severe hepato-renal insufficiency should not be examined unless absolutely indicated. Re-examination should be delayed for 5-7 days.

Niopam should be administered with caution in elderly patients and patients with increased intracranial pressure or suspicion of intracranial tumour, abscess or haematoma, and in those with a history of epilepsy, severe cardiovascular disease, renal impairment, chronic alcoholism or multiple sclerosis.

Patients with these conditions have an increased risk of neurological complications.

General anaesthesia may be indicated in selected patients. However, a higher incidence of adverse reactions has been reported in these patients, probably due to the hypotensive effect of the anaesthetic.

Contrast media may promote sickling in individuals who are homozygous for sickle cell disease when injected intravenously and intra-arterially.

Patients with phaeochromocytoma may develop severe hypertensive crisis following intravascular Niopam. Premedication with ?-receptor blockers is recommended.

The administration of iodinated contrast media may aggravate the symptoms of myasthenia gravis.

Patients with congestive heart failure should be observed for several hours following the procedure to detect delayed haemodynamic disturbances, which may be associated with a transitory increase in the circulating osmotic load. All other patients should be observed for at least one hour after the procedure, as most of the adverse events occur in this period. The patient should also be informed that allergic reactions may develop up to several days after the procedure; in such case, a physician should be consulted immediately.

In neonates, and particularly in premature neonates, it is recommended that tests of thyroid function (typically TSH and T4), should be checked 7-10 days and 1 month after the administration of iodinated contrast media because of the risk of hypothyroidism due to iodine overload.

In patients scheduled for thyroid examination with a radioactive iodine tracer, one must take into consideration that iodine uptake in the thyroid gland will be reduced for several days (up to two weeks) after dosing with an iodinized contrast medium that is eliminated through the kidneys.

Local tissue irritation can occur as an event of perivascular infiltration.

Neuroradiology

In patients who are known epileptics or have a history of epilepsy, anticonvulsant therapy should be maintained before and following myelographic procedures. In some instances anticonvulsant therapy may be increased for 48 hours before the examination.

Neuroleptics must be absolutely avoided because they lower the seizure threshold. The same applies to analgesics, antiemetics, antihistamines and sedatives of the phenothiazine group. Whenever possible, treatment with such drugs should be discontinued at least 48 hours before administration of the contrast medium and not be resumed less than 12 hours after completion of the procedure.

Angiography

In patients undergoing angiocardiographic procedures special attention should be paid to the status of the right heart and pulmonary circulation. Right heart insufficiency and pulmonary hypertension may precipitate bradycardia and systemic hypotension, when the organic iodine solution is injected. Right heart angiography should be carried out only when absolutely indicated.

In angiographic procedures, the possibility of dislodging plaque or damaging or perforating the vessel wall should be considered during catheter manipulation and contrast medium injection. Test injections to ensure proper catheter placements are recommended.

Angiography should be avoided whenever possible in patients with homocystinuria due to an increased risk of thrombosis and embolism.

In patients undergoing peripheral angiography, there should be pulsation in the artery into which the X-ray contrast medium will be injected. In patients with thromboangiitis obliterans or ascending infections in combination with serious ischemia the angiography should be performed, if at all, with special caution.

In patients undergoing venography, special caution should be exercised in patients with suspected phlebitis, serious ischaemia, local infections, or a complete venous occlusion. Serious neurological events have been observed following direct injection of contrast media into cerebral arteries or vessels supplying the spinal cord or in angiocardiography due to inadvertent filling of the carotids.

In paediatric roentgenology, one should proceed with great caution when injecting the contrast medium into the right heart chambers of cyanotic neonates with pulmonary hypertension and impaired cardiac function.

In examinations of the aortic arch the tip of the catheter should be positioned carefully to avoid hypotension, bradycardia and CNS injury due to excess pressure transmitted from the injector pump to the brachiocephalic branches of the aorta.

Urography

Care should be exercised in patients with moderate to severe impairment of renal function (as reflected by a raised blood urea). Substantial deterioration in renal function is minimized if the patient is well hydrated. Renal function parameters, especially urinary output should be monitored after the examination in these patients.

Re-examination should be delayed 5-7 days.

Non-ionic contrast media have less anti-coagulant activity in-vitro than ionic media. Meticulous attention should therefore be paid to angiographic technique. Non-ionic media should not be allowed to remain in contact with blood in the syringe and intravascular catheters should be flushed frequently, to minimise the risk of clotting, which rarely has led to serious thromboembolic complications after procedures.

Niopam should be used with caution in patients with hyperthyroidism. It is possible that hyperthyroidism may recur in patients previously treated for Graves' disease.

The presence of renal damage in diabetic patients is one of the factors predisposing to renal impairment following contrast media administration. This may precipitate lactic acidosis in patients who are taking metformin. As a precaution, metformin should be discontinued at the time of, or prior to, the procedure and withheld for 48 hours subsequent to the procedure and re-instituted only after renal function has been re-evaluated and found to be normal.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Thyroid function tests: use of iodinated contrast media may interfere with tests for thyroid function which depend on iodine estimations, such as Protein Binding Iodine and radioactive iodine uptake. As a consequence they will not accurately reflect thyroid function for up to 16 days following administration of iodinated contrast media. Thyroid function tests not depending on iodine estimations, e.g. T3 resin uptake and total or free thyroxine (T4) assays are not affected.

No other specific interference with physiological functions have been noted.

The administration of an X-ray contrast medium in diabetic patients with nephropathy who are taking biguanides may precipitate lactic acidosis.

Arterial thrombosis has been reported when iopamidol was given following papaverine.

The administration of vasopressors strongly potentiate the neurological effect of the intra-arterial contrast media.

Contrast media may interfere with laboratory tests for bilirubin, proteins or inorganic substances (eg iron, copper, calcium, phosphate). These substances should not be assayed during the same day following the administration of contrast media.

4.6 Pregnancy And Lactation

X-ray examination of women should if possible be conducted during the pre-ovulation phase of the menstrual cycle and should be avoided during pregnancy ; also, since it has not been demonstrated that Niopam is safe for use in pregnant women, it should be administered only if the procedure is considered essential by the physician.

Niopam is poorly excreted in human milk. From animal experience, Niopam is non toxic in animals after oral administration. Although, no serious adverse reactions have been reported in nursing infants, Niopam should be administered to lactating women only if considered essential by the physician.

4.7 Effects On Ability To Drive And Use Machines

There is no known effect on the ability to drive and operate machines. However, because of the risk of early reactions, driving or operating machinery is not advisable for one hour following the last injection.

4.8 Undesirable Effects

The use of iodinated contrast media may cause untoward side effects. They are usually mild to moderate and transient in nature. However , severe and life threatening reactions sometimes leading to death have been reported.

Anaphylaxis (anaphylactoid reactions/hypersensitivity) may manifest with: mild localized or more diffuse angioneurotic oedema, tongue oedema, laryngospasm or laryngeal oedema, dysphagia, pharyngitis and throat tightness, pharyngolaryngeal pain, cough, conjunctivitis, rhinitis, sneezing, feeling hot, sweating increased, asthenia, dizziness, pallor, dyspnoea, wheezing, bronchospasm, and moderate hypotension. Skin reactions may occur in the form of various types of rash, diffuse erythema, diffuse blisters, urticaria, and pruritus. These reactions, which occur irrespective of the dose administered and the route of administration, may represent the first signs of incipient state of shock. Administration of the contrast medium must be discontinued immediately and – if necessary – specific treatment initiated via a venous access.

More severe reactions involving the cardiovascular system such as vasodilatation with pronounced hypotension, tachycardia, dyspnoea, agitation, cyanosis and loss of consciousness (syncope) may require emergency treatment.

Intravascular administration –Adults

The safety of Iopamidol injection through intravascular administration was evaluated in 2,548 adult patients involved in clinical trials.

The adverse reactions are classified by System Organ Class and frequency, using the following convention: Very common (

System Organ Class

Adverse Reactions

     

Clinical Trials

Post-marketing Surveillance

     

Common

(

Uncommon

(

Rare

(

Frequency unknown

 

Blood and lymphatic system disorders

     

Thrombocytopenia

Immune system disorders

     

Anaphylaxis, Anaphylactoid reaction

Psychiatric disorders

   

Confusional state

 

Nervous system disorders

Headache

Dizziness, Taste alteration

Paraesthesia

Coma, Transient ischaemic attack, Syncope, Depressed level of consciousness or loss of consciousness, Convulsion,

Eye disorders

     

transient blindness, Visual disturbance, Conjunctivitis, Photophobia

Cardiac disorders

 

Cardiac dysrhythmias such as extrasystoles, atrial fibrillation, ventricular tachycardia and ventricular fibrillation*

Bradycardia

Myocardial ischaemia or infarction, Cardiac failure, Cardio-respiratory arrest, Tachycardia

Vascular disorders

 

Hypotension, Hypertension, Flushing

 

Circulatory collapse or shock

Respiratory, thoracic and mediastinal disorders

   

Pulmonary oedema, Asthma, Bronchospasm

Respiratory arrest, Respiratory failure, Acute respiratory distress syndrome, Respiratory distress, Apnoea, Laryngeal oedema, Dyspnoea

Gastrointestinal disorders

Nausea

Vomiting, Diarrhea, Abdominal pain, Dry mouth

 

Salivary hypersecretion, Salivary gland enlargement

Skin and subcutaneous tissue disorders

 

Rash, Urticaria, Pruritus, Erythema, Sweating increased

 

Face oedema, muco-cutaneous syndromes **

Musculoskeletal and connective tissue disorders

 

Back pain

Muscle spasms

Musculoskeletal pain, Muscular weakness

Renal and urinary disorders

 

Acute renal failure

   

General disorders and administration site conditions

Feeling hot

Chest pain, Injection site pain***, Pyrexia, Feeling cold

 

Rigors, Pain, Malaise

Investigations

 

Blood creatinine increased

 

Electrocardiogram change including ST segment depression

* Cardiac reactions may occur as consequences of the coronary catheterization procedural hazard: these complications include coronary artery thrombosis and coronary artery embolism.

** As with other iodinated contrast media, very rare cases of muco-cutaneous syndromes, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome) and erythema multiforme, have been reported following the administration of Iopamidol

*** Injection site pain and swelling may occur. In the majority of cases it is due to extravasation of contrast medium. These reactions are usually transient and result in recovery without sequelae. However, inflammation and even skin necrosis have been seen on very rare occasions. In isolated reports extravasation led to the development of compartment syndrome

Intravascular administration – Pediatric Population

Frequency type and severity of adverse reactions in children are similar to those in adults.

Intrathecal administration - Adults

The safety of Iopamidol injection through intrathecal administration was evaluated in 132 adult patients .

System Organ Class

Adverse Reactions

     

Clinical Trials

Post-marketing Surveillance

     

Very common

(

Common

(

Uncommon

(

Frequency unknown

 

Infections and infestations

     

Meningitis aseptic, Meningitis bacterial as consequence of the procedural hazard

Immune system disorders

     

Anaphylaxis, Anaphylactoid reaction*

Psychiatric disorders

     

Confusional state, Disorientation, Agitation, Restlessness

Nervous system disorders

Headache

   

Coma, Paralysis, Convulsion, Syncope, Depressed level of consciousness or loss of consciousness, Meningism,Dizziness, Paraesthesia, Hypoaesthesia

Eye disorders

     

Transient blindness

Cardiac disorders

     

Arrhythmia

Vascular disorders

 

Flushing

 

Hypertension

Respiratory, thoracic and mediastinal disorders

     

Respiratory arrest, Dyspnoea

Gastrointestinal disorders

 

Nausea, Vomiting

   

Skin and subcutaneous tissue disorders

   

Rash

 

Musculoskeletal and connective tissue disorders

 

Back pain, Neck pain, Pain in extremity, Sensation of heaviness

   

General disorders and administration site conditions

     

Pyrexia, Malaise, Rigors

* Anaphylaxis (anaphylactoid reactions/hypersensitivity) may occur. Anaphylactoid reactions with circulatory disturbances such as severe blood pressure decrease leading to syncope or cardiac arrest and life threatening shock are much less common after intrathecal administration than after intravascular administration.

Body cavity administration

The majority of the reactions occur some hours after the contrast administration due to the slow absorption from the area of administration and distribution in the whole organism.

The reactions reported in cases of arthrography usually represent irritative manifestations superimposed on existing tissue inflammation.

Systemic hypersensitivity is rare, generally mild and in the form of skin reactions. However, the possibility of severe anaphylactoid reactions cannot be excluded.

4.9 Overdose

Treatment of overdosage is directed toward the support of all vital functions and the elimination of the contrast medium while maintaining the patient well hydrated.

If needed, hemodyalisis can be used to eliminate iopamidol from the body.

5. Pharmacological Properties

Pharmacotherapeutic group; ATC code: V08A B04

5.1 Pharmacodynamic Properties

Iopamidol is contrast medium belonging to the new generation of non-ionic compound whose solubility is due to the presence of hydrophilic substitutes in the molecule. This results in a solution of low osmolality when compared with ionic media.

Iopamidol has been shown to be effective as an X-ray contrast medium in neuroradiology, angiography, venography, arthrography, urography, cerebral angiography and left ventriculography and coronary arteriography. Its toxicity particularly cardiac and CNS toxicity are less than those of ionic contrast media.

5.2 Pharmacokinetic Properties

The pharmacokinetics of iopamidol conform to an open two compartment pharmacokinetic model with first order elimination.

Distribution volume is equivalent to extracellular fluid.

Elimination is almost completely through the kidneys. Less that 1% of the administered dose has been recovered in the faeces up to 72 hours after dosing. Elimination is rapid; up to half the administered dose may be recovered in the urine in the first two hours of dosing.

There is no evidence of biotransformation.

Serum protein binding is negligible.

5.3 Preclinical Safety Data

No adverse effects can be predicted from animal toxicology studies other than those documented from human use of iopamidol.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Excipients are trometamol, hydrochloric acid and edetate calcium disodium.

6.2 Incompatibilities

No other drug should be mixed with the contrast medium.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Protect from light.

6.5 Nature And Contents Of Container

10ml clear, colourless Type I glass ampoules.

20 and 30ml clear, colourless Type I or Type II glass vials with rubber closures and aluminium caps.

20, 50, 70, 100, 200 and 250ml clear, colourless Type I or Type II glass bottles with rubber closures and aluminium caps.

6.6 Special Precautions For Disposal And Other Handling

Discard if the solution is not clear of particulate matter.

Exceptionally, the event of crystallisation of Niopam could occur. It has been shown that such a phenomenon is caused by a damaged or defective container and therefore the product should not be used in this case.

The bottle, once opened, must be used immediately.

Any residue of contrast medium must be discarded.

Niopam, as other iodinated contrast media, can react with metallic surfaces containing copper (e.g. brass), therefore the use of equipment, in which the product comes into direct contact with such surfaces, should be avoided.

7. Marketing Authorisation Holder

Bracco U.K. Ltd,

Bracco House, Mercury Park,

Wycombe Lane, Wooburn Green,

Buckinghamshire HP10 OHH

8. Marketing Authorisation Number(S)

PL 18920/0009

9. Date Of First Authorisation/Renewal Of The Authorisation

22nd March 1982/ 9th January 2002

10. Date Of Revision Of The Text

15 November 2011

Nitrodur 0.6

Generic Name: nitroglycerin (Transdermal route)

nye-troe-GLIS-er-in

Commonly used brand name(s)

In the U.S.

Minitran Nitrek Nitro-Bid Nitro-Dur

In Canada

Nitrodur 0.2 Nitro-Dur 0.2 Nitro-Dur 0.3 Nitrodur 0.4 Nitro-Dur 0.4 Nitrodur 0.6 Nitro-Dur 0.6 Nitro-Dur 0.8 Transderm-Nitro Trinipatch 0.2 Trinipatch 0.4 Trinipatch 0.6

Available Dosage Forms:

Ointment Patch, Extended Release

Therapeutic Class: Antianginal

Chemical Class: Nitrate

Uses For Nitrodur 0.6

Nitroglycerin transdermal is used to prevent angina (chest pain) caused by coronary artery disease. It does not work fast enough to relieve the pain of an angina attack that has already started.

Nitroglycerin transdermal belongs to the group of medicines called nitrates. It works by relaxing the blood vessels and increasing the supply of blood and oxygen to the heart while reducing its work load. When used regularly on a long-term basis, this helps prevent angina attacks from occurring.

This medicine is available only with your doctor's prescription.

Before Using Nitrodur 0.6

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of nitroglycerin transdermal in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of nitroglycerin transdermal in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving nitroglycerin transdermal.

Pregnancy Pregnancy Category Explanation All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Sildenafil Tadalafil Vardenafil

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Alteplase, Recombinant

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Acetylcysteine Aspirin Dihydroergotamine Pancuronium Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

Cardioversion (medical heart procedure) or Defibrillation (medical heart procedure)—Use with caution. The patch should be removed before having these procedures. Congestive heart failure or Heart attack, recent or Hypertrophic cardiomyopathy (a heart disease) or Hypotension (low blood pressure) or Hypovolemia (low amount of blood)—Use with caution. May make these conditions worse. Proper Use of nitroglycerin

This section provides information on the proper use of a number of products that contain nitroglycerin. It may not be specific to Nitrodur 0.6. Please read with care.

Use this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. It will only work if applied correctly.

This form of nitrate is used to reduce the number of angina attacks over a long time. It will not relieve an attack that has already started because it works too slowly. The ointment and patch forms release medicine gradually to provide an effect for 7 to 10 hours. Check with your doctor if you also need a fast-acting medicine to relieve the pain of an angina attack.

You should use this medicine first thing in the morning and follow the same schedule each day. This medicine works best if you have a "drug-free" period of time every day when you do not use it. Your doctor will schedule your doses during the day to allow for a drug-free time. Follow the schedule of dosing carefully so the medicine will work properly.

This medicine comes with a patient information leaflet. Read and follow the instructions in the leaflet carefully. Ask your doctor if you have any questions.

For patients using the ointment:

Before applying a new dose of ointment, remove any ointment remaining on the skin from a previous dose. This will allow the fresh ointment to release the nitroglycerin properly. This medicine comes with papers to help measure the dose. Use them to measure the length of ointment squeezed from the tube and to apply the ointment to the skin. Do not rub or massage the ointment into the skin. Spread it in a thin, even layer, and cover an area of skin that is the same size each time it is applied. Apply the ointment to skin with little or no hair that is free of scars, cuts, or irritation. Apply each dose of ointment to a different area of skin to prevent irritation. If your doctor has ordered an airtight covering or dressing (such as plastic kitchen wrap) be placed over this medicine, make sure you know how to apply it. Airtight dressings will increase the amount of medicine absorbed through the skin and may cause more side effects. Use them only as directed and check with your doctor if you have any questions about this.

For patients using the patch system:

Wash your hands with soap and water before and after applying a patch. Do not touch your eyes until after you have washed your hands. Do not try to trim or cut the adhesive patch to adjust the dosage. Check with your doctor if you think the medicine is not working as it should. Apply the patch to a clean, dry skin area with little or no hair that is free of scars, cuts, or irritation. Always remove a previous patch before applying a new one. Apply a new patch if the first one becomes loose or falls off. Apply each patch to a different area to prevent skin irritation. Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For angina prevention: For transdermal dosage form (ointment): Adults—At first, 7.5 milligrams (mg), one-half inch of ointment, two times a day. Apply the first dose in the morning right after you wake up, and the second dose 6 hours later. Your doctor may increase your dose as needed. Children—Use and dose must be determined by your doctor. For transdermal dosage form (skin patch): Adults—Apply one patch once a day in the morning. Leave the patch in place for a total of 12 to 14 hours. Children—Use and dose must be determined by your doctor. Missed Dose

If you miss a dose of this medicine, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

After removing a used patch, fold it in half with the sticky sides together. Make sure to dispose of it out of the reach of children and pets.

Precautions While Using Nitrodur 0.6

If you will be taking this medicine for a long time, it is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Do not take sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®) while you are using this medicine. Using these medicines together may cause blurred vision, dizziness, lightheadedness, or fainting. If you are taking these medicines and you experience an angina attack, you must go to the hospital right away.

This medicine may cause headaches. These headaches are a sign that the medicine is working. Do not stop using the medicine or change the time you use it in order to avoid the headaches. If you have severe pain, talk with your doctor.

Dizziness, lightheadedness, or faintness may occur, especially when you get up quickly from a lying or sitting position. Getting up slowly may help.

Dizziness, lightheadedness, or fainting is also more likely to occur if you drink alcohol, stand for long periods of time, exercise, or if the weather is hot. While you are taking this medicine, be careful to limit the amount of alcohol you drink. Also, use extra care during exercise or hot weather or if you must stand for long periods of time.

Do not stop using this medicine without checking with your doctor first. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Tell the doctor in charge that you are using this medicine before having a magnetic resonance imaging (MRI) scan. Skin burns may occur at the site where the patch is worn during this procedure. Ask your doctor if the patch should be removed before having an MRI scan. You might need to put on a new patch after the procedure.

Nitrodur 0.6 Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common Lightheadedness Less common Arm, back, or jaw pain blurred vision chest pain or discomfort chest tightness or heaviness confusion dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly fainting fast or irregular heartbeat nausea shortness of breath sweating unusual tiredness or weakness Rare Bluish-colored lips, fingernails, or palms dark urine difficulty with breathing fever headache pale skin rapid heart rate sore throat unusual bleeding or bruising Incidence not known Blistering, burning, crusting, dryness, or flaking of the skin cough difficulty with swallowing hives itching, scaling, severe redness, soreness, or swelling of the skin puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue skin rash wheezing

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose Blurred or loss of vision bulging soft spot on the head of an infant change in consciousness change in the ability to see colors, especially blue or yellow cold, clammy skin disturbed color perception double vision feeling of constant movement of self or surroundings halos around lights headache, severe and throbbing loss of consciousness night blindness overbright appearance of lights paralysis sensation of spinning tunnel vision

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Rare Burning, itching, redness, skin rash, swelling, or soreness at the application site

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Nitrodur 0.6 side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Nitrodur 0.6 resources Nitrodur 0.6 Side Effects (in more detail)Nitrodur 0.6 Use in Pregnancy & BreastfeedingNitrodur 0.6 Drug InteractionsNitrodur 0.6 Support Group0 Reviews for Nitrodur 0.6 - Add your own review/rating Compare Nitrodur 0.6 with other medications AnginaAngina Pectoris ProphylaxisHeart AttackHeart FailureHigh Blood Pressure

Neutrogena Lotion

Generic Name: topical emollients (TOP i kal ee MOL i ents) Brand Names: Aloe Vesta Cream, AlphaSoft, AmeriPhor, Aqua Glycolic, Aqua Lube, Aquaphor, Aveeno, Baby Lotion, Baby Oil, Bag Balm, Baza-Pro, Beta Care, Blistex Lip Balm, Carmex, CarraKlenz, CeraVe, CeraVe AM, Cetaphil Lotion, Chap Stick, Citraderm, CoolBottoms, Corn Huskers Lotion, Curel Moisture Lotion, Derma Soothe, Dr Scholl's Essentials Cracked Skin Repair, Eucerin, Herpecin-L, K-Y Jelly, Keri Lotion, Lamisilk Heel Balm, Lubri-Soft, Lubriderm, Mederma, Moisturel, Natural Ice, NeutrapHor, NeutrapHorus Rex, Neutrogena Cleansing, Neutrogena Lotion, Nivea, Nutraderm, Pacquin, Phisoderm, Pretty Feet & Hands, Proshield Skincare Kit, Remedy 4-in-1 Cleansing Lotion, Replens, Secura, Sensi-Care, Soft Sense, St. Ives, Theraplex Lotion, Vaseline Intensive Care

What are Neutrogena Lotion (topical emollients)?

Emollients are substances that moisten and soften your skin.

Topical (for the skin) emollients are used to treat or prevent dry skin. Topical emollients are sometimes contained in products that also treat acne, chapped lips, diaper rash, cold sores, or other minor skin irritation.

There are many brands and forms of topical emollients available and not all are listed on this leaflet.

Topical emollients may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Neutrogena Lotion (topical emollients)? You should not use a topical emollient if you are allergic to it. Topical emollients will not treat or prevent a skin infection.

Ask a doctor or pharmacist before using this medication if you have deep wounds or open sores, swelling, warmth, redness, oozing, bleeding, large areas of skin irritation, or any type of allergy.

What should I discuss with my healthcare provider before using Neutrogena Lotion (topical emollients)? You should not use a topical emollient if you are allergic to it. Topical emollients will not treat or prevent a skin infection.

Ask a doctor or pharmacist if it is safe for you to use this medicine if you have:

deep wounds or open sores;

swelling, warmth, redness, oozing, or bleeding;

large areas of skin irritation;

any type of allergy; or

if you are pregnant or breast-feeding. How should I use Neutrogena Lotion (topical emollients)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Clean the skin where you will apply the topical emollient. It may help to apply this product when your skin is wet or damp. Follow directions on the product label.

Shake the product container if recommended on the label.

Apply a small amount of topical emollient to the affected area and rub in gently.

If you are using a stick, pad, or soap form of topical emollient, follow directions for use on the product label.

Do not use this product over large area of skin. Do not apply a topical emollient to a deep puncture wound or severe burn without medical advice.

If your skin appears white or gray and feels soggy, you may be applying too much topical emollient or using it too often.

Some forms of topical emollient may be flammable and should not be used near high heat or open flame, or applied while you are smoking.

Store as directed away from moisture, heat, and light. Keep the bottle, tube, or other container tightly closed when not in use.

What happens if I miss a dose?

Since this product is used as needed, it does not have a daily dosing schedule. Seek medical advice if your condition does not improve after using a topical emollient.

What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. What should I avoid while taking Neutrogena Lotion (topical emollients)? Avoid getting topical emollients in your eyes, nose, or mouth. If this does happen, rinse with water. Avoid exposure to sunlight or tanning beds. Some topical emollients can make your skin more sensitive to sunlight or UV rays. Neutrogena Lotion (topical emollients) side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using the topical emollient and call your doctor if you have severe burning, stinging, redness, or irritation where the product was applied.

Less serious side effects are more likely, and you may have none at all.

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 Neutrogena Lotion (topical emollients)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied products. But many drugs can interact with each other. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Neutrogena Lotion resources Neutrogena Lotion Use in Pregnancy & BreastfeedingNeutrogena Lotion Support Group0 Reviews for Neutrogena - Add your own review/rating Biafine Emulsion MedFacts Consumer Leaflet (Wolters Kluwer) Campath Monograph (AHFS DI) Campral Monograph (AHFS DI) Camptosar Monograph (AHFS DI) Diabinese Monograph (AHFS DI) Kinerase Cream MedFacts Consumer Leaflet (Wolters Kluwer) Neosalus Foam MedFacts Consumer Leaflet (Wolters Kluwer) Promiseb Cream MedFacts Consumer Leaflet (Wolters Kluwer) Compare Neutrogena Lotion with other medications Dry Skin Where can I get more information? Your pharmacist can provide more information about topical emollients.

Nizoral Shampoo
Generic Name: ketoconazole Dosage Form: shampooNizoral® (ketoconazole) 2% Shampoo Nizoral Shampoo Description

NIZORAL® (ketoconazole) 2% Shampoo is a red-orange liquid for topical application, containing the broad spectrum synthetic antifungal agent ketoconazole in a concentration of 2% in an aqueous suspension. It also contains: coconut fatty acid diethanolamide, disodium monolauryl ether sulfosuccinate, F.D.&C. Red No. 40, hydrochloric acid, imidurea, laurdimonium hydrolyzed animal collagen, macrogol 120 methyl glucose dioleate, perfume bouquet, sodium chloride, sodium hydroxide, sodium lauryl ether sulfate, and purified water.

Ketoconazole is cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3 - dioxolan-4-yl]methoxy]phenyl]piperazine and has the following structural formula:

Nizoral Shampoo - Clinical Pharmacology

Tinea (pityriasis) versicolor is a non-contagious infection of the skin caused by Pityrosporum orbiculare (Malassezia furfur). This commensal organism is part of the normal skin flora. In susceptible individuals the condition is often recurrent and may give rise to hyperpigmented or hypopigmented patches on the trunk which may extend to the neck, arms and upper thighs. Treatment of the infection may not immediately result in restoration of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental skin exposure. The rate of recurrence of infection is variable.

NIZORAL® (ketoconazole) was not detected in plasma in 39 patients who shampooed 4–10 times per week for 6 months, or in 33 patients who shampooed 2–3 times per week for 3–26 months (mean: 16 months).

An exaggerated use washing test on the sensitive antecubital skin of 10 subjects twice daily for five consecutive days showed that the irritancy potential of ketoconazole 2% shampoo was significantly less than that of 2.5% selenium sulfide shampoo.

A human sensitization test, a phototoxicity study, and a photoallergy study conducted in 38 male and 22 female volunteers showed no contact sensitization of the delayed hypersensitivity type, no phototoxicity and no photoallergenic potential due to NIZORAL® (ketoconazole) 2% Shampoo.

Mode of Action: Interpretations of in vivo studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated, but not proven, that the therapeutic effect of ketoconazole in tinea (pityriasis) versicolor is due to the reduction of Pityrosporum orbiculare (Malassezia furfur) and that the therapeutic effect in dandruff is due to the reduction of Pityrosporum ovale. Support for the therapeutic effect in tinea versicolor comes from a three-arm, parallel, double-blind, placebo controlled study in patients who had moderately severe tinea (pityriasis) versicolor. Successful response rates in the primary efficacy population for each of both three-day and single-day regimens of ketoconazole 2% shampoo were statistically significantly greater (73% and 69%, respectively) than a placebo regimen (5%). There had been mycological confirmation of fungal disease in all cases at baseline. Mycological clearing rates were 84% and 78%, respectively, for the three-day and one-day regimens of the 2% shampoo and 11% in the placebo regimen. While the differences in the rates of successful response between either of the two active treatments and placebo were statistically significant, the difference between the two active regimens was not.

Microbiology: NIZORAL® (ketoconazole) is a broad spectrum synthetic antifungal agent which inhibits the growth of the following common dermatophytes and yeasts by altering the permeability of the cell membrane: dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. audouini, M. gypseum and Epidermophyton floccosum; yeasts: Candida albicans, C. tropicalis, Pityrosporum ovale (Malassezia ovale) and Pityrosporum orbiculare (M. furfur). Development of resistance by these microorganisms to ketoconazole has not been reported.

Indications and Usage for Nizoral Shampoo

NIZORAL® (ketoconazole) 2% Shampoo is indicated for the treatment of tinea (pityriasis) versicolor caused by or presumed to be caused by Pityrosporum orbiculare (also known as Malassezia furfur or M. orbiculare).

Note: Tinea (pityriasis) versicolor may give rise to hyperpigmented or hypopigmented patches on the trunk which may extend to the neck, arms and upper thighs. Treatment of the infection may not immediately result in normalization of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental sun exposure. Although tinea versicolor is not contagious, it may recur because the organism that causes the disease is part of the normal skin flora.

Contraindications

NIZORAL® (ketoconazole) 2% Shampoo is contraindicated in persons who have known hypersensitivity to the active ingredient or excipients of this formulation.

Precautions

Severe hypersensitivity reactions, including anaphylaxis, have been reported during post-marketing use of NIZORAL® (ketoconazole) Shampoo. If a reaction suggesting sensitivity or chemical irritation should occur, use of the medication should be discontinued.

Information for Patients:

Patients should be advised of the following:

NIZORAL® (ketoconazole) 2% Shampoo may be irritating to mucous membranes of the eyes and contact with this area should be avoided.

Nastrosa 1mg film-coated tablets
1. Name Of The Medicinal Product

Nastrosa 1mg film-coated tablets

2. Qualitative And Quantitative Composition

Each tablet contains 1 mg anastrozole as active substance.

Excipients: Each tablet contains 90.3 mg lactose (as lactose monohydrate).

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-coated tablet.

White, round, biconvex, film-coated tablets. Debossed with '1' on one side and plain on the reverse side.

4. Clinical Particulars 4.1 Therapeutic Indications

Treatment of advanced breast cancer in postmenopausal women.

Efficacy has not been demonstrated in oestrogen receptor-negative patients unless they had a previous positive clinical response to tamoxifen.

4.2 Posology And Method Of Administration

Adults including the elderly:

One 1 mg tablet to be taken orally once a day.

Children:

Not recommended for use in children.

Renal impairment:

No dose change is recommended in patients with mild or moderate renal impairment.

Hepatic impairment:

No dose change is recommended in patients with mild hepatic disease.

 

4.3 Contraindications

Anastrozole is contraindicated in:

- premenopausal women.

- pregnant or lactating women.

- patients with severe renal impairment (creatinine clearance less than 20 ml / min)

- patients with moderate or severe hepatic disease

- patients with hypersensitivity to anastrozole or to any of the excipients as referenced in section 6.1.

Oestrogen-containing therapies should not be co-administered with anastrozole as they would negate its pharmacological action.

Concurrent tamoxifen therapy (see section 4.5)

4.4 Special Warnings And Precautions For Use

Anastrozole is not recommended for use in children as safety and efficacy have not been established in this group of patients.

The menopause should be defined biochemically in any patient where there is doubt about hormonal status.

There are no data to support the safe use of anastrozole in patients with moderate or severe hepatic impairment, or patients with severe impairment of renal function (creatinine clearance less than 20 ml/min).

Women with osteoporosis or at risk of osteoporosis, should have their bone mineral density formally assessed by bone densitometry e.g. DEXA scanning at the commencement of treatment and at regular intervals thereafter. Treatment or prophylaxis for osteoporosis should be initiated as appropriate and carefully monitored.

There are no data available for the use of anastrozole with LHRH analogues. This combination should not be used outside clinical trials.

As anastrozole lowers circulating oestrogen levels it may cause a reduction in bone mineral density. Adequate data to show the effect of bisphosphonates on bone mineral density loss caused by anastrozole, or their utility when used prophylactically, are not currently available.

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Anastrozole inhibited cytochrome P450 1A2, 2C8/9 and 3A4 in vitro. A clinical interaction study indicated that anastrozole at a 1 mg dose does not significantly alter the pharmacokinetics of warfarin, a CYP2C9 substrate.

No clinically significant interactions between anastrozole and bisphosphonates have been identified.

Antipyrine and cimetidine clinical interaction studies indicate that co-administration of anastrozole with other drugs is unlikely to result in clinically significant drug interactions mediated by cytochrome P450.

A review of the clinical trial safety datatbase did not reveal evidence of clinically significant interaction in patients treated with anastrozole who also received other commonly prescribed drugs.

Tamoxifen should not be co-administered with anastrozole, as this may diminish its pharmacological action (see section 4.3).

4.6 Pregnancy And Lactation

Anastrozole is contraindicated in pregnant or lactating women.

Pregnancy

There are no data on the use of anastrozole in pregnant patients. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Anastrozole 1mg should not be used in pregnancy.

Lactation

It is unknown whether anastrozole is excreted in human milk. Anastrozole 1mg should nor be used during breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

Anastrozole is unlikely to impair the ability of patients to drive and operate machinery. However, asthenia and somnolence have been reported with the use of anastrozole and caution should be observed when driving or operating machinery while such symptoms persist.

4.8 Undesirable Effects

The assessment of the side effects is based on the following frequencies:

Very common (

Common (

Uncommon (

Rare (

Very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Nervous system disorders

Common: Headache, mainly mild or moderate in nature

Carpal Tunnel Syndrome

Uncommon: Somnolence, mainly mild or moderate in nature

Gastrointestinal disorders

Common: Nausea, mainly mild or moderate in nature, diarrhoea, mainly mild or moderate

Uncommon: Vomiting, mainly mild or moderate in nature

Skin and subcutaneous tissue disorders

Common: Hair thinning, mainly mild or moderate in nature, Rash, mainly mild or moderate in nature

Very rare: Erythema multiforme, Stevens-Johnson syndrome, allergic reactions including angiooedema, urticaria and anaphylaxis

Musculoskeletal and connective tissue disorders

Common: Joint pain/stiffness, mainly mild or moderate in nature

Metabolism and nutrition disorders

Uncommon: Anorexia, mainly mild in nature, hypercholesterolaemia, mainly mild or moderate in nature

Vascular disorders

Very common: Hot flushes, mainly mild or moderate in nature

General disorders and administration site conditions

Common: Asthenia, mainly mild or moderate in nature

Hepatobiliary disorders

Common: Increases in alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase

Uncommon: Increases in gamma-GT and bilirubin, hepatitis

Reproductive system and breast disorders

Common: Vaginal dryness, mainly mild or moderate in nature

Uncommon: Vaginal bleeding, mainly mild or moderate in nature*

*Vaginal bleeding has been reported uncommonly, mainly in patients with advanced breast cancer during the first few weeks after changing from existing hormonal therapy to treatment with anastrozole. If bleeding persists, further evaluation should be considered.

As anastrozole lowers circulating oestrogen levels, it may cause a reduction in bone mineral density placing some patients at a higher risk of fracture (see section 4.4).

Elevated gamma-GT has been reported uncommonly (

The table below presents the frequency of pre-specified adverse events in the ATAC study, irrespective of causality, reported in patients receiving trial therapy and up to 14 days after cessation of trial therapy.

Adverse effects

Anastrozole

(N=3092)

Tamoxifen

(N=3094)

Hot flushes

1104 (35.7%)

1264 (40.9%)

Joint pain/stiffness

1100 (35.6%)

911 (29.4%)

Mood disturbances

597 (19.3%)

554 (17.9%)

Fatigue/asthenia

575 (18.6%)

544 (17.6%)

Nausea and vomiting

393 (12.7%)

384 (12.4%)

Fractures

315 (10.2%)

209 (6.8%)

Fractures of the spine, hip, or wrist/Colles

133 (4.3%)

91 (2.9%)

Wrist/Colles fractures

67 (2.2%)

50 (1.6%)

Spine fractures

43 (1.4%)

22 (0.7%)

Hip fractures

28 (0.9%)

26 (0.8%)

Cataracts

182 (5.9%)

213 (6.9%)

Vaginal bleeding

167 (5.4%)

317 (10.2%)

Ischaemic cardiovascular disease

127 (4.1%)

104 (3.4%)

Angina pectoris

71 (2.3%)

51 (1.6%)

Myocardial infarct

37 (1.2%)

34 (1.1%)

Coronary artery disorder

25 (0.8%)

23 (0.7%)

Myocardial ischaemia

22 (0.7%)

14 (0.5%)

Vaginal discharge

109 (3.5%)

408 (13.2%)

Any venous thromboembolic event

87 (2.8%)

140 (4.5%)

Deep venous thromboembolic events including PE

48 (1.6%)

74 (2.4%)

Ischaemic cerebrovascular events

62 (2.0%)

88 (2.8%)

Endometrial cancer

4 (0.2%)

13 (0.6%)

Fracture rates of 22 per 1000 patient-years and 15 per 1000 patient-years were observed for the anastrozole and tamoxifen groups, respectively, after a median follow-up of 68 months. The observed fracture rate for anastrozole is similar to the range reported in age-matched postmenopausal populations. It has not been determined whether the rates of fracture and osteoporosis seen in ATAC in patients on anastrozole treatment reflect a protective effect of tamoxifen, a specific effect of anastrozole, or both. The incidence of osteoporosis was 10.5% in patients treated with anastrozole and 7.3% in patients treated with tamoxifen.

4.9 Overdose

There is limited clinical experience of accidental overdosage. In animal studies, anastrozole demonstrated low acute toxicity. Clinical trials have been conducted with various dosages of anastrozole, up to 60 mg in a single dose given to healthy male volunteers and up to 10 mg daily given to postmenopausal women with advanced breast cancer; these dosages were well tolerated. A single dose of anastrozole that results in life-threatening symptoms has not been established. There is no specific antidote to overdosage and treatment must be symptomatic.

In the management of an overdose, consideration should be given to the possibility that multiple agents may have been taken. Vomiting may be induced if the patient is alert. Dialysis may be helpful because anastrozole is not highly protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antineoplastic and immunomodulating agents – Endocrine therapy – Hormone antagonists and related agents – Enzyme inhibitors.

ATC code: L02B G03

Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. In postmenopausal women, estradiol is produced primarily from the conversion of androstenedione to estrone through the aromatase enzyme complex in peripheral tissues. Estrone is subsequently converted to estradiol. Reducing circulating estradiol levels has been shown to produce a beneficial effect in women with breast cancer. In postmenopausal women, anastrozole at a daily dose of 1 mg produced estradiol suppression of greater than 80% using a highly sensitive assay.

Anastrozole does not possess any progestogenic, androgenic or oestrogenic activity. Daily doses of anastrozole up to 10 mg do not have any effect on cortisol or aldosterone secretion, measured before or after standard ACTH challenge testing. Corticoid supplements are therefore not needed.

An extensive phase III clinical study programme showed that anastrozole is an effective treatment of hormone-receptor positive breast cancer in post menopausal women.

5.2 Pharmacokinetic Properties

Absorption of anastrozole is rapid and maximum plasma concentrations typically occur within two hours of dosing (under fasted conditions). Anastrozole is eliminated slowly with a plasma elimination half-life of 40 to 50 hours. Food slightly decreases the rate but not the extent of absorption. The small change in the rate of absorption is not expected to result in a clinically significant effect on steady-state plasma concentrations during once daily dosing of anastrozole. Approximately 90 to 95% of plasma anastrozole steady-state concentrations are attained after 7 daily doses. There is no evidence of time or dose-dependency of anastrozole pharmacokinetic parameters.

Anastrozole pharmacokinetics are independent of age in postmenopausal women.

Pharmacokinetics have not been studied in children.

Anastrozole is only 40% bound to plasma proteins.

Anastrozole is extensively metabolised by postmenopausal women with less than 10% of the dose excreted in the urine unchanged within 72 hours of dosing. Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. The metabolites are excreted primarily via the urine. Triazole, the major metabolite in plasma, does not inhibit aromatase.

The apparent oral clearance of anastrozole in volunteers with stable hepatic cirrhosis or renal impairment was in the range observed in healthy volunteers.

5.3 Preclinical Safety Data

Acute toxicity

In acute toxicity studies in rodents, the median lethal dose of anastrozole was greater than 100 mg/kg/day by the oral route and greater than 50 mg/kg/day by the intraperitoneal route. In an oral acute toxicity study in the dog, the median lethal dose was greater than 45 mg/kg/day.

Chronic toxicity

Multiple dose toxicity studies utilized rats and dogs. No no-effect levels were established for anastrozole in the toxicity studies, but those effects that were observed at the low doses (1 mg/kg/day) and mid doses (dog 3 mg/kg/day; rat 5 mg/kg/day) were related to either the pharmacological or enzyme-inducing properties of anastrozole and were unaccompanied by significant toxic or degenerative changes.

Mutagenicity

Genetic toxicology studies with anastrozole show that it is not a mutagen or a clastogen.

Reproductive toxicology

Oral administration of anastrozole to female rats produced a high incidence of infertility at 1 mg/kg/day and increased pre-implantation loss at 0.02 mg/kg/day. These effects occurred at clinically relevant doses. An effect in man cannot be excluded. These effects were related to the pharmacology of the compound and were completely reversed after a 5-week compound withdrawal period.

Oral administration of anastrozole to pregnant rats and rabbits caused no teratogenic effects at doses up to 1.0 and 0.2 mg/kg/day respectively. Those effects that were seen (placental enlargement in rats and pregnancy failure in rabbits) were related to the pharmacology of the compound.

The survival of litters born to rats given anastrozole at 0.02 mg/kg/day and above (from day 17 of pregnancy to day 22 post-partum) was compromised. These effects were related to the pharmacological effects of the compound on parturition. There were no adverse effects on behaviour or reproductive performance of the first generation offspring attributable to maternal treatment with anastrozole.

Carcinogenicity

A two year rat oncogenicity study resulted in an increase in incidence of hepatic neoplasms and uterine stromal polyps in females and thyroid adenomas in males at the high dose (25 mg/kg/day) only. These changes occurred at a dose which represents 100-fold greater exposure than occurs at human therapeutic doses, and are considered not to be clinically relevant to the treatment of patients with anastrozole.

A two year mouse oncogenicity study resulted in the induction of benign ovarian tumours and a disturbance in the incidence of lymphoreticular neoplasms (fewer histiocytic sarcomas in females and more deaths as a result of lymphomas). These changes are considered to be mouse-specific effects of aromatase inhibition and not clinically relevant to the treatment of patients with anastrozole.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Tablet core:

Lactose monohydrate

Sodium starch glycolate (Type A)

Magnesium stearate

Film coating:

Opadry II white 85F18422 consisting of

Poly (vinyl alcohol) –partially hydrolysed

Titanium dioxide

Macrogol 3350

Talc

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

2 years

6.4 Special Precautions For Storage

This medicinal product does not require any special storage conditions

6.5 Nature And Contents Of Container

PVC/PVDC aluminium blisters.

Pack sizes :

20, 28, 30. 84, 98, 100 and 300 film-coated tablets

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Niche Generics Limited,

1 The Cam Centre,

Wilbury Way,

Hitchin,

Hertfordshire,

SG4 0TW,

United Kingdom.

8. Marketing Authorisation Number(S)

PL 19611/0157.

9. Date Of First Authorisation/Renewal Of The Authorisation

3rd December 2009.

10. Date Of Revision Of The Text

January 2011

Nalfrx Suspension
Pronunciation: DEX-klor-fen-IR-a-meen/SOO-doe-e-FED-rin/pir-IL-a-meenGeneric Name: Dexchlorpheniramine/Pseudoephedrine/PyrilamineBrand Name: Nalfrx

Napratec OP
1. Name Of The Medicinal Product

NAPRATEC™ OP

2. Qualitative And Quantitative Composition

Napratec is a combination pack containing 56 Naproxen 500mg tablets and 56 Cytotec (misoprostol) 200mcg tablets.

For excipients, see 6.1

3. Pharmaceutical Form

Tablet

Naproxen 500mg tablets are yellow, oblong and engraved 'NXN500' with a breakline on one side and CP on the reverse.

Cytotec is a white/off-white hexagonal tablet, scored on both sides, engraved SEARLE 1461 on one side.

4. Clinical Particulars 4.1 Therapeutic Indications

Napratec combination pack is indicated for patients who require Naproxen 500mg twice daily and Cytotec 200mcg twice daily.

Naproxen is indicated for the treatment of rheumatoid arthritis, osteoarthritis (degenerative arthritis) and ankylosing spondylitis.

Cytotec is indicated for the prophylaxis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastroduodenal ulceration.

4.2 Posology And Method Of Administration

For oral administration

Adults

1 tablet of Naproxen and 1 tablet of Cytotec to be taken together twice daily with or after food.

Elderly

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly.

With Cytotec the usual dosage may be used in the elderly.

Napratec should only be used in those patients for whom 500mg naproxen twice daily is appropriate and in whom no reduction of naproxen dosage is necessary (see also sections on renal and hepatic impairment).

The elderly are at an increased risk of the serious consequences of adverse reactions. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Renal Impairment

As the final pathway for the elimination of naproxen metabolites is largely (95%) by urinary excretion via glomerular filtration it should be used with great caution in patients with impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. Naproxen is not recommended in patients having a baseline creatinine clearance of less than 20ml/minute.

Certain patients, specifically those whose renal blood flow is compromised, such as in extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure, and pre-existing renal disease, should have renal function assessed before and during naproxen therapy. Some elderly patients in whom impaired renal function may be expected could also fall within this category. Where there is a possibility of accumulation of naproxen metabolites, such patients may not be suitable to receive naproxen 500mg twice daily.

With Cytotec no dosage alteration is necessary in patients with impaired renal function.

Hepatic Impairment

Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased.

With Cytotec no dosage alteration is necessary in patients with impaired hepatic function.

Children

Napratec is not recommended.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

4.3 Contraindications

Use in Pregnancy and Lactation

Napratec is contraindicated in pregnancy and lactation (see section 4.6)

This medicine is also contraindicated in patients planning to become pregnant.

Napratec is contraindicated in patients with a known hypersensitivity to naproxen, or to misoprostol or to any of the excipients.

As the potential exists with naproxen for cross-sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs, Napratec should not be administered to patients in whom aspirin, ibuprofen and other NSAIDs induce asthma, rhinitis, urticaria or angioedema.

As Napratec is a "prevention pack" it should not be used for treating arthritis in patients with active gastric or duodenal ulceration / haemorrhage. Such patients may be treated with a healing dose of Cytotec, 800 micrograms daily in divided doses with meals, and the NSAID continued or discontinued at the physician's discretion.

Use in pre-menopausal women

Napratec should not be used in pre-menopausal women unless the patient is at high risk of complications from NSAID-induced ulceration. In such patients it is advised that Napratec should only be used if the patient:

- takes effective contraceptive measures

- has been advised of the risks of taking the product if pregnant

Napratec is contraindicated in patients with severe heart failure, hepatic failure and renal failure (see section 4.4).

4.4 Special Warnings And Precautions For Use

Precautions

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

The use of Naproxen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

Naproxen, in common with other NSAIDs, decreases platelet aggregation and prolongs bleeding time. This effect should be considered when bleeding times are determined.

Elderly:

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2)

Respiratory disorders:

Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma or allergic disease since NSAIDs have been reported to precipitate bronchospasm in such patients.

Cardiovascular, Renal and Hepatic Impairment:

The administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3).

Mild peripheral oedema has been observed in a few patients receiving naproxen. Although sodium retention has not been reported in metabolic studies, it is possible that patients with questionable or compromised cardiac function may be at a greater risk when taking naproxen.

Cardiovascular and cerebrovascular effects:

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Although data suggest that the use of naproxen (1000 mg daily) may be associated with a lower risk, some risk cannot be excluded.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with naproxen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Gastrointestinal bleeding, ulceration and perforation:

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events. When GI bleeding or ulceration occurs in patients receiving Napratec OP, the treatment should be withdrawn. The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly.

Patients with a history of GI toxicity, particularly if complicated when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin. (see section 4.5)

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8)

Dermatological:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with use of NSAID (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy: onset of the reaction occurring in the majority of cases within the first month of treatment. Napratec should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Sporadic abnormalities in laboratory tests (e.g. liver function tests) have occurred in patients on naproxen, but no definite trend was seen in any test indicating toxicity.

Cytotec should be used with caution in disease states where hypotension might precipitate severe complications, e.g. cerebrovascular disease, coronary artery disease or severe peripheral vascular disease including hypertension.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Drug Interactions

Due to the high plasma protein binding of naproxen, patients simultaneously receiving hydantoins, anti-coagulants or a highly protein-bound sulphonamide should be observed for signs of over dosage of these drugs. No interactions have been observed in clinical studies with naproxen and anti-coagulants or sulphonylureas, but caution is nevertheless advised since interaction has been seen with other non-steroidal agents of this class.

Diuretics: NSAIDs may attenuate the natriuretic efficacy of diuretics due to inhibition of intrarenal synthesis of prostaglandins. NSAIDs may also cause a reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Ciclosporin: Because of their effect on renal prostaglandins, cyclo-oxygenase inhibitors such as naproxen can increase the nephrotoxicity of ciclosporin

Other analgesics including cyclooxygenase-2-selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse events (see section 4.4).

Lithium: NSAIDs including naproxen have been reported to increase steady state plasma lithium levels. It is recommended that these are monitored whenever initiating, adjusting or discontinuing naproxen products.

Cardiac glycosides: Concomitant administration of Naproxen with cardiac glycosides may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Anti-hypertensives: Concomitant administration of naproxen with beta-blockers may reduce their antihypertensive effect.

Corticosteroids: Concomitant administration of naproxen with corticosteroids increases the risk of gastrointestinal ulceration or bleeding (see section 4.4) and may increase the frequency of side effects generally.

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Probenecid: Increases naproxen plasma levels and extends its plasma half-life considerably.

Methotrexate: Caution is advised when methotrexate is administered concurrently because of possible enhancement of its toxicity since naproxen, among other NSAIDs, has been reported to induce the tubular secretion of methotrexate in an animal model.

Mifepristone: NSAIDs should not be used for 8 – 12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulatnts, such as warfarin (see section 4.4).

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Naproxen therapy should be temporarily withdrawn before adrenal function tests are performed as it may artificially interfere with some tests for 17-ketogenic steroids. Similarly, naproxen may interfere with some assays of urinary 5-hydroxyindoleacetic acid.

Cytotec is predominantly metabolised via fatty acid oxidising systems and has shown no adverse effect on the hepatic microsomal mixed function oxidase (P450) enzyme system. No drug interactions have been attributed to Cytotec, and in specific studies, no clinically significant pharmacokinetic or pharmacodynamic interaction has been demonstrated with antipyrine, diazepam, propranolol or NSAIDs.

4.6 Pregnancy And Lactation

Napratec is contraindicated in pregnancy and lactation. The product is contraindicated in pregnancy on the basis that Cytotec is contraindicated in pregnancy or women planning a pregnancy as it increases uterine tone and contractions in pregnancy which may cause partial or complete expulsion of the products of conception.

Teratology studies with naproxen in rats and rabbits at dose levels equivalent on a human multiple basis to those which have produced foetal abnormality with certain other NSAIDs, e.g. aspirin, have not produced evidence of foetal damage with naproxen. As with other drugs of this type, naproxen delays parturition in animals (the relevance of this finding to human patients is unknown) and also affects the human foetal cardiovascular system (closure of the ductus arteriosus).

4.7 Effects On Ability To Drive And Use Machines

Dizziness, drowsiness, fatigue, visual disturbances or headaches are possible undesirable effects after taking NSAIDs. If affected, patients should not drive or operate machinery.

4.8 Undesirable Effects

Naproxen:

Gastrointestinal: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, particularly in the elderly may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain or discomfort and epigastric distress, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following administration. The more serious reaction, colitis, may occasionally occur. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.

Naproxen also causes gastrointestinal bleeding and gastric and duodenal ulceration, the consequences of which may be haemorrhage and perforation. The inclusion of Cytotec in the combination pack is to prevent naproxen-induced gastric and duodenal ulceration.

Hypersensitivity and Dermatological: Non-specific allergic reactions and anaphylaxis, respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, assorted skin disorders including rashes of various types,, pruritus, purpura, urticaria, angio-oedema.. Anaphylactic reactions to naproxen and naproxen sodium formulations; eosinophilic pneumonitis, alopecia, photosensitivity reactions and more rarely epidermolysis bullosa, epidermal necrolysis, erythema multiforme, pseudoporphyria, Stevens Johnson syndrome and toxic epidermal necrolysis (very rare).

Cardiovascular and cerebrovascular:

Oedema, hypertension, and cardiac failure, have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Neurological and special senses: Headache, visual disturbances, insomnia, optic neuritis, paraesthesia, inability to concentrate, cognitive dysfunction, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4), depression, confusion, hallucinations, tinnitus, hearing impairment, vertigo, dizziness, malaise, fatigue and drowsiness.

Renal: As a class NSAIDs have been associated with renal pathology including nephropathy, papillary necrosis, interstitial nephritis, nephrotic syndrome and renal failure.

Hepatic: Abnormal liver function, fatal hepatitis and jaundice.

Haematological: Thrombocytopenia, neutropenia, granulocytopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia may occur rarely.

Other: Mild peripheral oedema, vasculitis, and haematuria.

Cytotec:

Gastrointestinal: Diarrhoea has been reported and is occasionally severe and prolonged, and may require withdrawal of the drug. It can be minimised by taking Cytotec with food and by avoiding the use of predominantly magnesium-containing antacids when an antacid is required. Abdominal pain with or without associated dyspepsia can follow Cytotec therapy. Other gastrointestinal adverse effects reported include dyspepsia, flatulence, nausea and vomiting.

Female Reproductive System: Menorrhagia, vaginal bleeding and intermenstrual bleeding have been reported in both pre- and post-menopausal women.

Other Adverse Effects: Skin rashes have been reported. Dizziness has been infrequently reported.

4.9 Overdose

Naproxen:

Symptoms - Symptoms include drowsiness, heartburn, indigestion, nausea, vomiting, headache, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientataion, excitation, coma, dizziness, tinnitus, fainting, occasionally convulsions. A few patients have experienced seizures, but it is not clear whether these were naproxen-related or not. In cases of significant poisoning acute renal failure and liver damage are possible. It is not known what dose of the drug would be life-threatening.

Therapeutic measures - In the event of overdosage with naproxen, the stomach may be emptied and usual supportive measures employed.

• Patients should be treated symptomatically as required.

• Within one hour of ingestion of a potential toxic amount, activated charcoal should be considered. Animal studies indicate that the prompt administration of activated charcoal in adequate amounts would tend to reduce markedly the absorption of the drug. Alternatively, in adult, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.

• Good urine output should be insured.

• Renal and liver function should be closely monitored

• Patients should be observed for at least four hours after ingestion of potentially toxic amounts

• Frequent or prolonged convulsions should be treated with intravenous diazepam

• Other measures may be indicated by the patient's clinical condition.

Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding. However, haemodialysis may still be appropriate in a patient with renal failure who has taken naproxen.

Cytotec:

Intensification of pharmacological and adverse effects may occur with overdose. In the event of overdosage with Cytotec, symptomatic and supportive therapy should be given as appropriate.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Naproxen is a non-steroidal anti-inflammatory drug with well-documented properties, i.e. analgesic, antipyretic and anti-inflammatory.

Misoprostol is a synthetic prostaglandin E1 analogue which enhances several of the factors that maintain gastroduodenal mucosal integrity.

5.2 Pharmacokinetic Properties

Naproxen is readily absorbed from the GI tract. Peak plasma concentrations are obtained 2-4 hours after ingestion. At therapeutic concentrations, naproxen is more than 98% bound to plasma proteins and has an elimination half-life of between 12-15 hours.

Misoprostol is rapidly absorbed following oral administration with peak plasma levels of the active metabolite (misoprostol acid) occurring after about 30 minutes. The plasma elimination half-life of misoprostol acid is 20-40 minutes.

Increases in Cmax and AUC for misoprostol acid have been observed when co-administered with naproxen in a single dose study. These changes are not thought to be clinically significant since the higher values are still well within the variation seen after 200 micrograms misoprostol in other studies. No accumulation of misoprostol acid in plasma occurs after repeated dosing of 400 micrograms twice daily.

5.3 Preclinical Safety Data

Naproxen causes gastric erosions when given orally or subcutaneously to fasting rats. There is no evidence of mutagenicity or carcinogenicity when administered to rats in studies of two years duration. There is no evidence of teratogenicity in mice, rats or rabbits.

Misoprostol in multiples of the recommended therapeutic dose in animals has produced gastric mucosal hyperplasia. This characteristic response to E-series prostaglandins reverts to normal on discontinuation of the compound.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Naproxen 500mg tablets contain: Lactose, maize starch, povidone, sodium starch glycolate, magnesium stearate, yellow lake CLF 3076 (E104 and E172).

Cytotec 200mcg tablets contain: microcrystalline cellulose, sodium starch glycolate, hydrogenated castor oil and hypromellose.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 30?C. Store in the original package.

6.5 Nature And Contents Of Container

Combination pack containing 8 x 7 day blisters containing 56 Naproxen 500mg tablets and 56 Cytotec 200mcg tablets in cold-formed aluminium blisters.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent, CT13 9NJ

United Kingdom

8. Marketing Authorisation Number(S)

PL00057/1018

9. Date Of First Authorisation/Renewal Of The Authorisation

26 June 2002

10. Date Of Revision Of The Text

June 2011

11. LEGAL CATEGORY

POM

Ref: NA 5_0 UK

2 3 4 5 6 7 8 9 10 11 12 13 Next →