GONAL f 1050 IU 1.75 ml 77mcg 1.75 ml

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Follicle Stimulation Medications

Drugs associated with Follicle Stimulation

The following drugs and medications are in some way related to, or used in the treatment of Follicle Stimulation. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Follicle Stimulation

Medical Encyclopedia:

Infertility
Drug List: Bravelle Fertinex Follistim Follistim-Aq Follistim-Aq-Cartridge Gonal-F-Powder Gonal-F-Rff Gonal-F-Rff-Pen-Solution Luveris Menopur Metrodin Repronex

Ovulation Induction Medications

Definition of Ovulation Induction: Techniques for the artifical induction of ovulation.

Drugs associated with Ovulation Induction

The following drugs and medications are in some way related to, or used in the treatment of Ovulation Induction. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Drug List: Cetrotide Chorex Chorionic-Gonadotropin Clomid Follistim Follistim-Aq Follistim-Aq-Cartridge Gonal-F-Powder Gonal-F-Rff Gonal-F-Rff-Pen-Solution Hcg Menopur Novarel Ovidrel Pregnyl Profasi Profasi-Hp Repronex Serophene

Gonadotropins

A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.

Gonadotropins are hormones synthesized and released by the anterior pituitary, and act on the gonads (testes and ovaries) to promote production of sex hormones and stimulate production of either sperm or ova. Follicle stimulating hormone (FSH) and luteinizing hormones (LH) are the main gonadotropins. Human chorionic gonadotropin is a gonadotropin that is only produced during pregnancy by the placenta.

Gonadotropin production is controlled by gonadotropin-releasing hormone, which is released by the hypothalamus. The effects of gonadotrophins differ in males and females.

Gonadotropins are used in fertility treatment to produce mature follicles and ovulation induction, in women. In men, it is used to increase sperm count as part of fertility treatment.

Gonal-f Powder

Pronunciation: FALL-lee-tro-pin
Generic Name: Follitropin Alfa
Brand Name: Gonal-f
Gonal-f Powder is used for:

Treating infertility in certain patients. It may also be used for other conditions as determined by your doctor.

Gonal-f Powder is a human follicle-stimulating hormone. It is used to treat infertility in women by stimulating the ovaries to produce eggs.It is used to treat male infertility by increasing sperm count. Gonal-f Powder is usually given with other medicines.

Do NOT use Gonal-f Powder if: you are allergic to any ingredient in Gonal-f Powder you are allergic to sucrose, sodium phosphate, or benzyl alcohol you have uncontrolled thyroid or adrenal problems you have pituitary tumor or other brain lesion or tumor you have hormone-sensitive tumors you have primary ovarian failure (eg, your ovaries do not make eggs) you are pregnant or think you may be pregnant you have cancer in your female organs (eg, ovaries, breast, uterus) you have heavy or irregular bleeding from your uterus or vagina you have ovarian cysts or enlargement, not due to polycystic ovary syndrome (PCOS)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Gonal-f Powder:

Some medical conditions may interact with Gonal-f Powder. Tell your health care provider if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement if you have allergies to medicines or other substances if you have urinary tract bleeding if you have an adrenal gland or thyroid problem if you have permanent damage to the testes if you have swollen, enlarged, or painful ovaries if you have blood-clotting problems or breathing problems (eg, asthma)

Some MEDICINES MAY INTERACT with Gonal-f Powder. Tell your health care provider if you are taking any other medicines.

Ask your health care provider if Gonal-f Powder may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Gonal-f Powder:

Use Gonal-f Powder as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Gonal-f Powder. Talk to your pharmacist if you have questions about this information. Gonal-f Powder is usually administered as an injection at your doctor's office, hospital, or clinic. If you will be using Gonal-f Powder at home, a health care provider will teach you how to use it. Be sure you understand how to use Gonal-f Powder. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions. Do not use Gonal-f Powder if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged. Do not touch the needle or allow it to touch any surface. The duration of treatment will be determined by your health care provider. It is recommended that a couple using Gonal-f Powder has intercourse daily, starting on the day before the injection of Gonal-f Powder. If you miss a dose of Gonal-f Powder, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Gonal-f Powder.

Important safety information: Gonal-f Powder may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Gonal-f Powder with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. Women will need to have a complete gynecological and hormone evaluation prior to starting therapy with Gonal-f Powder. Your partner should be evaluated for fertility problems. Men will need to have a complete medical and hormone evaluation before starting therapy with Gonal-f Powder. Ovarian hyperstimulation syndrome (OHSS) is a severe side effect that may occur in some women who use Gonal-f Powder. Contact your doctor right away if you develop severe stomach pain or bloating; nausea, vomiting, or diarrhea; sudden unexplained weight gain; shortness of breath; or decreased urination. Gonal-f Powder may cause multiple births (eg, twins). Talk with your doctor to discuss your chances of multiple births. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Lab tests, such as ultrasound or drawing an estradiol level, may be performed while you use Gonal-f Powder. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments. Gonal-f Powder is not for use in the ELDERLY; safety and effectiveness in the elderly have not been confirmed. Gonal-f Powder should not be used in CHILDREN; safety and effectiveness in children have not been confirmed. PREGNANCY and BREAST-FEEDING: Do not use Gonal-f Powder if you are pregnant. If you think you may be pregnant, contact your doctor right away. If you are or will be breast-feeding while you use Gonal-f Powder, check with your doctor. Discuss any possible risks to your baby. Possible side effects of Gonal-f Powder:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Acne; breast pain or growth; discomfort at the injection site; headache; sinus infection; stomach upset; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal vaginal bleeding; calf pain or tenderness; chest pain; confusion; fever; one-sided weakness; severe or persistent shortness of breath; severe pelvic or back pain; signs of OHSS (eg, decreased urination; diarrhea; severe or persistent stomach pain, upset or bloating; nausea; sudden unexplained weight gain; vomiting); slurred speech; unusual vaginal itching, discharge, or odor; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Gonal-f side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms of overdose may include nausea; severe headache; severe stomach pain or swelling; vomiting; weakness; weight gain.

Proper storage of Gonal-f Powder:

Store Gonal-f Powder in the refrigerator (36 to 46 degrees F; 2 to 8 degrees C) until the expiration date. It can be kept at room temperature (68 to 77 degrees F; 20 to 25 degrees C) for up to 1 month or until the expiration date, whichever comes first. Once Gonal-f Powder is mixed, it should be used immediately. Do not store medicine that has been mixed. Protect from light. Do not freeze. Keep Gonal-f Powder out of the reach of children and away from pets.

General information: If you have any questions about Gonal-f Powder, please talk with your doctor, pharmacist, or other health care provider. Gonal-f Powder is to be used only by the patient for whom it is prescribed. Do not share it with other people. If your symptoms do not improve or if they become worse, check with your doctor. Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Gonal-f Powder. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012 Database Edition 12.1.1.002 Copyright © 2012 Wolters Kluwer Health, Inc. More Gonal-f resources Gonal-f Side Effects (in more detail) Gonal-f Use in Pregnancy & Breastfeeding Gonal-f Drug Interactions Gonal-f Support Group 2 Reviews for Gonal-f - Add your own review/rating Compare Gonal-f with other medications Follicle Stimulation Hypogonadism, Male Ovulation Induction

Gonal-f RFF Pen

Generic Name: follicle stimulating hormone (FOL ik al STIM ue lay ting HOR mone)
Brand Names: Follistim AQ, Follistim AQ Cartridge, Gonal-F, Gonal-f RFF, Gonal-f RFF Pen

What is Gonal-f RFF Pen (follicle stimulating hormone)?

Follicle stimulating hormone is a man-made form of a hormone that occurs naturally in the body. This hormone regulates ovulation, the growth and development of eggs in a woman's ovaries.

Follicle stimulating hormone is used to treat infertility in women who cannot ovulate and do not have primary ovarian failure. Follicle stimulating hormone is also used to stimulate sperm production in men.

Follicle stimulating hormone is often used together with another medication called human chorionic gonadotropin (hCG).

Follicle stimulating hormone may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Gonal-f RFF Pen (follicle stimulating hormone)? Do not use this medication if you are already pregnant. Your doctor may give you a pregnancy test to make sure you are not pregnant before you receive follicle stimulating hormone.

Follicle stimulating hormone is not effective in women with primary ovarian failure or in men with primary testicular failure.

You should not use this medicine if you are allergic to follicle stimulating hormone, neomycin (Mycifradin, Neo-Fradin) or streptomycin, or if you have an untreated or uncontrolled endocrine disorder (thyroid, pituitary gland, or adrenal gland), heavy or abnormal vaginal bleeding that has not been checked by a doctor, an ovarian cyst, or cancer of the breast, ovary, uterus, or testicle.

Before using follicle stimulating hormone, tell your doctor if you have polycystic ovary disease, asthma, or a history of stroke or blood clot.

You should not breast-feed while you are using follicle stimulating hormone. Avoid having sex and call your doctor right away if you have any of the following symptoms of a fluid buildup in your stomach or chest area: severe pain in your lower stomach, nausea, vomiting, diarrhea, bloating, feeling short of breath, swelling or weight gain, or urinating less than usual.

Fertility treatment may increase your chance of having twins, triplets, etc (multiple births). These are high-risk pregnancies both for the mother and the babies. Talk to your doctor if you have concerns about this risk.

What should I discuss with my healthcare provider before using Gonal-f RFF Pen (follicle stimulating hormone)?

This medication is not effective in women with primary ovarian failure (when the ovaries are unable to produce an egg).

This medication is not effective in men with primary testicular failure (when the testicles are unable to produce sperm).

You should not use follicle stimulating hormone if you are allergic to it, if you are already pregnant, or if you have:

an untreated or uncontrolled disorder of the thyroid, pituitary gland, or adrenal glands;

heavy or abnormal vaginal bleeding that has not been checked by a doctor;

an ovarian cyst;

cancer of the breast, ovary, uterus, testicle, hypothalamus, or pituitary gland; or

if you are allergic to neomycin (Mycifradin, Neo-Fradin) or streptomycin.

To make sure you can safely use follicle stimulating hormone, tell your doctor if you have:

polycystic ovary disease;

asthma; or

a history of stroke or blood clot.

FDA pregnancy category X. Follicle stimulating hormone can harm an unborn baby or cause birth defects. Do not use this medication if you are already pregnant. Your doctor may give you a pregnancy test to make sure you are not pregnant before you receive follicle stimulating hormone. Tell your doctor right away if you become pregnant during treatment.

It is not known whether follicle stimulating hormone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using follicle stimulating hormone. How should I use Gonal-f RFF Pen (follicle stimulating hormone)? You must remain under the care of a doctor while using follicle stimulating hormone.

Follicle stimulating hormone is injected under the skin or into a muscle. You will be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

The cartridge and injection pen are used only for an injection under the skin. Follicle stimulating hormone in a vial (bottle) is for injection into a muscle using a syringe.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Your doctor may occasionally change your dose to make sure you get the best results.

Prepare your syringe or injection pen only when you are ready to give yourself an injection. Do not use the medication if it looks cloudy or has particles in it. Call your doctor for a new prescription.

Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

If you use follicle stimulating hormone to get pregnant, you may need to have sex daily for several days in a row. The timing of sex within your dosing schedule is important for this treatment to work.

To be sure this medication is helping your condition, your blood may need to be tested often. You may also need ultrasound exams. Visit your doctor regularly.

Storing unopened vials, cartridges, or injection pens: Keep in the carton and store in a refrigerator or at room temperature. Do not freeze. Protect from light and use within 3 months.

Storing after your first use: Keep the vial, cartridge, or injection pen at room temperature or in the refrigerator and use within 28 days. Protect from light.

Take the injection pen out of the refrigerator and allow it to reach room temperature before giving the injection. Do not heat the medicine before using.

Throw away any unused vial, cartridge, or pen after the expiration date on the label has passed.

Do not share this medication with another person, even if they have the same symptoms you have. What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of follicle stimulating hormone.

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 using Gonal-f RFF Pen (follicle stimulating hormone)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Gonal-f RFF Pen (follicle stimulating hormone) side effects Some women using this medicine have developed a sudden buildup of fluid in the stomach or chest area. This condition is called ovarian hyperstimulation syndrome (OHSS), and can be a life-threatening. Avoid having sex and call your doctor right away if you have any of the following symptoms of OHSS:

severe pain in your lower stomach;

nausea, vomiting, diarrhea, bloating;

feeling short of breath;

swelling in your hands or legs;

weight gain;

urinating less than usual.

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 follicle stimulating hormone and call your doctor at once if you have a serious side effect such as:

sudden numbness or weakness (especially on one side of the body);

pain, swelling, warmth, or redness in your arms or legs; or

severe pelvic pain on one side.

Less serious side effects may include:

headache;

mild nausea or stomach pain;

mild numbness or tingly feeling;

mild pelvic pain, tenderness, or discomfort;

runny or stuffy nose, sore throat;

breast swelling or tenderness;

acne;

mild skin rash; or

pain, bruising, redness, or irritation where the injection was given.

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 Gonal-f RFF Pen (follicle stimulating hormone)?

There may be other drugs that can interact with follicle stimulating hormone. 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 Gonal-f RFF Pen resources Gonal-f RFF Pen Side Effects (in more detail)Gonal-f RFF Pen Use in Pregnancy & BreastfeedingGonal-f RFF Pen Drug InteractionsGonal-f RFF Pen Support Group0 Reviews for Gonal-f RFF Pen - Add your own review/rating Gonal-f RFF Pen Solution MedFacts Consumer Leaflet (Wolters Kluwer) Follistim Consumer Overview Follistim Advanced Consumer (Micromedex) - Includes Dosage Information Follistim AQ Consumer Overview Follistim AQ MedFacts Consumer Leaflet (Wolters Kluwer) Follistim AQ Prescribing Information (FDA) Gonal-F Prescribing Information (FDA) Gonal-F Advanced Consumer (Micromedex) - Includes Dosage Information Gonal-f Powder MedFacts Consumer Leaflet (Wolters Kluwer) Gonal-f RFF Prescribing Information (FDA) Compare Gonal-f RFF Pen with other medications Follicle StimulationHypogonadism, MaleOvulation Induction Where can I get more information? Your doctor or pharmacist can provide more information about follicle stimulating hormone.

See also: Gonal-f RFF Pen side effects (in more detail)

GONAL-f 1050 IU / 1.75 ml (77mcg / 1.75 ml)

1. Name Of The Medicinal Product

GONAL-f 1050 IU/1.75 ml (77 micrograms/1.75 ml) powder and solvent for solution for injection.

2. Qualitative And Quantitative Composition

Each vial contains 77 micrograms of follitropin alfa* equivalent to 1050 IU. Each ml of the reconstituted solution contains 600 IU.

* recombinant human follicle stimulating hormone (r-hFSH) produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Powder and solvent for solution for injection.

Appearance of the powder: white lyophilised pellet.

Appearance of the solvent: clear colourless solution.

The pH of the reconstituted solution is 6.5-7.5.

4. Clinical Particulars 4.1 Therapeutic Indications

In adult women

• Anovulation (including polycystic ovarian syndrome) in women who have been unresponsive to treatment with clomiphene citrate.

• Stimulation of multifollicular development in women undergoing superovulation for assisted reproductive technologies (ART) such as in vitro fertilisation (IVF), gamete intra-fallopian transfer and zygote intra-fallopian transfer.

• GONAL-f in association with a luteinising hormone (LH) preparation is recommended for the stimulation of follicular development in women with severe LH and FSH deficiency. In clinical trials these patients were defined by an endogenous serum LH level < 1.2 IU/l.

In adult men

• GONAL-f is indicated for the stimulation of spermatogenesis in men who have congenital or acquired hypogonadotrophic hypogonadism with concomitant human Chorionic Gonadotropin (hCG) therapy.

4.2 Posology And Method Of Administration

Treatment with GONAL-f should be initiated under the supervision of a physician experienced in the treatment of fertility disorders.

Posology

The dose recommendations given for GONAL-f are those in use for urinary FSH. Clinical assessment of GONAL-f indicates that its daily doses, regimens of administration, and treatment monitoring procedures should not be different from those currently used for urinary FSH-containing medicinal products. It is advised to adhere to the recommended starting doses indicated below.

Comparative clinical studies have shown that on average patients require a lower cumulative dose and shorter treatment duration with GONAL-f compared with urinary FSH. Therefore, it is considered appropriate to give a lower total dose of GONAL-f than generally used for urinary FSH, not only in order to optimise follicular development but also to minimise the risk of unwanted ovarian hyperstimulation. See section 5.1.

Bioequivalence has been demonstrated between equivalent doses of the monodose presentation and the multidose presentation of GONAL-f.

The following table states the volume to be administered to deliver the prescribed dose:

Dose (IU)

Volume to be injected (ml)

0.13

150

0.25

225

0.38

300

0.50

375

0.63

450

0.75

The next injection should be done at the same time the next day.

Women with anovulation (including polycystic ovarian syndrome)

GONAL-f may be given as a course of daily injections. In menstruating women treatment should commence within the first 7 days of the menstrual cycle.

A commonly used regimen commences at 75-150 IU FSH daily and is increased preferably by 37.5 or 75 IU at 7 or preferably 14 day intervals if necessary, to obtain an adequate, but not excessive, response. Treatment should be tailored to the individual patient's response as assessed by measuring follicle size by ultrasound and/or oestrogen secretion. The maximal daily dose is usually not higher than 225 IU FSH. If a patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned and the patient should undergo further evaluation after which she may recommence treatment at a higher starting dose than in the abandoned cycle.

When an optimal response is obtained, a single injection of 250 micrograms recombinant human choriogonadotropin alfa (r-hCG) or 5,000 IU, up to 10,000 IU hCG should be administered 24-48 hours after the last GONAL-f injection. The patient is recommended to have coitus on the day of, and the day following, hCG administration. Alternatively intrauterine insemination (IUI) may be performed.

If an excessive response is obtained, treatment should be stopped and hCG withheld (see section 4.4). Treatment should recommence in the next cycle at a dose lower than that of the previous cycle.

Women undergoing ovarian stimulation for multiple follicular development prior to in vitro fertilisation or other assisted reproductive technologies.

A commonly used regimen for superovulation involves the administration of 150-225 IU of GONAL-f daily, commencing on days 2 or 3 of the cycle. Treatment is continued until adequate follicular development has been achieved (as assessed by monitoring of serum oestrogen concentrations and/or ultrasound examination), with the dose adjusted according to the patient's response, to usually not higher than 450 IU daily. In general adequate follicular development is achieved on average by the tenth day of treatment (range 5 to 20 days).

A single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG is administered 24-48 hours after the last GONAL-f injection to induce final follicular maturation.

Down-regulation with a gonadotropin-releasing hormone (GnRH) agonist or antagonist is now commonly used in order to suppress the endogenous LH surge and to control tonic levels of LH. In a commonly used protocol, GONAL-f is started approximately 2 weeks after the start of agonist treatment, both being continued until adequate follicular development is achieved. For example, following two weeks of treatment with an agonist, 150-225 IU GONAL-f are administered for the first 7 days. The dose is then adjusted according to the ovarian response.

Overall experience with IVF indicates that in general the treatment success rate remains stable during the first four attempts and gradually declines thereafter.

Women with anovulation resulting from severe LH and FSH deficiency.

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of GONAL-f therapy in association with lutropin alfa is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotropin (hCG). GONAL-f should be given as a course of daily injections simultaneously with lutropin alfa. Since these patients are amenorrhoeic and have low endogenous oestrogen secretion, treatment can commence at any time.

A recommended regimen commences at 75 IU of lutropin alfa daily with 75-150 IU FSH. Treatment should be tailored to the individual patient's response as assessed by measuring follicle size by ultrasound and oestrogen response.

If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day intervals and preferably by 37.5-75 IU increments. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.

When an optimal response is obtained, a single injection of 250 micrograms r-hCG or 5,000 IU up to 10,000 IU hCG should be administered 24-48 hours after the last GONAL-f and lutropin alfa injections. The patient is recommended to have coitus on the day of, and on the day following, hCG administration.

Alternatively, IUI may be performed.

Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum.

If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.

Men with hypogonadotrophic hypogonadism

GONAL-f should be given at a dose of 150 IU three times a week, concomitantly with hCG, for a minimum of 4 months. If after this period, the patient has not responded, the combination treatment may be continued; current clinical experience indicates that treatment for at least 18 months may be necessary to achieve spermatogenesis.

Special population

Elderly population

There is no relevant use of GONAL-f in the elderly population. Safety and effectiveness of GONAL-f in elderly patients have not been established.

Renal or hepatic impairment

Safety, efficacy and pharmacokinetics of GONAL-f in patients with renal or hepatic impairment have not been established.

Paediatric population

There is no relevant use of GONAL-f in the paediatric population.

Method of administration

GONAL-f is intended for subcutaneous administration. The first injection of GONAL-f should be performed under direct medical supervision. Self-administration of GONAL-f should only be performed by patients who are well motivated, adequately trained and have access to expert advice.

As GONAL-f multidose is intended for several injections, clear instructions should be provided to the patients to avoid misuse of the multidose presentation.

Due to a local reactivity to benzyl alcohol, the same site of injection should not be used on consecutive days.

Individual reconstituted vials should be for single patient use only.

For instructions on the reconstitution and administration of GONAL-f powder and solvent for solution for injection see section 6.6 and the package leaflet.

4.3 Contraindications

• hypersensitivity to the active substance follitropin alfa, FSH or to any of the excipients

• tumours of the hypothalamus or pituitary gland

• ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome

• gynaecological haemorrhages of unknown aetiology

• ovarian, uterine or mammary carcinoma

GONAL-f must not be used when an effective response cannot be obtained, such as:

• primary ovarian failure

• malformations of sexual organs incompatible with pregnancy

• fibroid tumours of the uterus incompatible with pregnancy

• primary testicular insufficiency

4.4 Special Warnings And Precautions For Use

GONAL-f is a potent gonadotrophic substance capable of causing mild to severe adverse reactions, and should only be used by physicians who are thoroughly familiar with infertility problems and their management.

Gonadotropin therapy requires a certain time commitment by physicians and supportive health professionals, as well as the availability of appropriate monitoring facilities. In women, safe and effective use of GONAL-f calls for monitoring of ovarian response with ultrasound, alone or preferably in combination with measurement of serum oestradiol levels, on a regular basis. There may be a degree of interpatient variability in response to FSH administration, with a poor response to FSH in some patients and exaggerated response in others. The lowest effective dose in relation to the treatment objective should be used in both men and women.

Porphyria

Patients with porphyria or a family history of porphyria should be closely monitored during treatment with GONAL-f. Deterioration or a first appearance of this condition may require cessation of treatment.

Treatment in women

Before starting treatment, the couple's infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinemia and appropriate specific treatment given.

Patients undergoing stimulation of follicular growth, whether as treatment for anovulatory infertility or ART procedures, may experience ovarian enlargement or develop hyperstimulation. Adherence to recommended GONAL-f dose and regimen of administration and careful monitoring of therapy will minimise the incidence of such events. For accurate interpretation of the indices of follicle development and maturation, the physician should be experienced in the interpretation of the relevant tests.

In clinical trials, an increase of the ovarian sensitivity to GONAL-f was shown when administered with lutropin alfa. If an FSH dose increase is deemed appropriate, dose adaptation should preferably be at 7-14 day intervals and preferably with 37.5-75 IU increments.

No direct comparison of GONAL-f/LH versus human menopausal gonadotropin (hMG) has been performed. Comparison with historical data suggests that the ovulation rate obtained with GONAL-f/LH is similar to that obtained with hMG.

Ovarian Hyperstimulation Syndrome (OHSS)

A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is more commonly seen in women with polycystic ovarian syndrome and usually regresses without treatment.

In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities.

The following symptomatology may be observed in severe cases of OHSS: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, or acute pulmonary distress. Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events such as pulmonary embolism, ischaemic stroke or myocardial infarction.

Independent risk factors for developing OHSS include polycystic ovarian syndrome high absolute or rapidly rising serum oestradiol levels (e.g. > 900 pg/ml or > 3,300 pmol/l in anovulation; > 3,000 pg/ml or > 11,000 pmol/l in ART) and large number of developing ovarian follicles (e.g. > 3 follicles of

Adherence to recommended GONAL-f dose and regimen of administration can minimise the risk of ovarian hyperstimulation (see sections 4.2 and 4.8). Monitoring of stimulation cycles by ultrasound scans as well as oestradiol measurements are recommended to early identify risk factors.

There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may be more severe and more protracted if pregnancy occurs. Therefore, if signs of ovarian hyperstimulation occur such as serum oestradiol level > 5,500 pg/ml or > 20,200 pmol/l and/or

In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.

Mild or moderate OHSS usually resolves spontaneously. If severe OHSS occurs, it is recommended that gonadotropin treatment be stopped if still ongoing, and that the patient be hospitalised and appropriate therapy be started.

Multiple pregnancy

In patients undergoing ovulation induction, the incidence of multiple pregnancy is increased compared with natural conception. The majority of multiple conceptions are twins. Multiple pregnancy, especially of high order, carries an increased risk of adverse maternal and perinatal outcomes.

To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.

In patients undergoing ART procedures the risk of multiple pregnancy is related mainly to the number of embryos replaced, their quality and the patient age.

The patients should be advised of the potential risk of multiple births before starting treatment.

Pregnancy loss

The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing stimulation of follicular growth for ovulation induction or ART than following natural conception.

Ectopic pregnancy

Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy after ART, was reported to be higher than in the general population.

Reproductive system neoplasms

There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility treatment. It is not yet established whether or not treatment with gonadotropins increases the risk of these tumours in infertile women.

Congenital malformation

The prevalence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, sperm characteristics) and multiple pregnancies.

Thromboembolic events

In women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for thromboembolic events, such as personal or family history, treatment with gonadotropins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotropin administration need to be weighed against the risks. It should be noted however that pregnancy itself as well as OHSS also carry an increased risk of thromboembolic events.

Treatment in men

Elevated endogenous FSH levels are indicative of primary testicular failure. Such patients are unresponsive to GONAL-f/hCG therapy. GONAL-f should not be used when an effective response cannot be obtained.

Semen analysis is recommended 4 to 6 months after the beginning of treatment as part of the assessment of the response.

Sodium content

GONAL-f contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant use of GONAL-f with other medicinal products used to stimulate ovulation (e.g. hCG, clomiphene citrate) may potentiate the follicular response, whereas concurrent use of a GnRH agonist or antagonist to induce pituitary desensitisation may increase the dose of GONAL-f needed to elicit an adequate ovarian response. No other clinically significant medicinal product interaction has been reported during GONAL-f therapy.

4.6 Pregnancy And Lactation

Pregnancy

There is no indication for use of GONAL-f during pregnancy. Data on a limited number of exposed pregnancies (less than 300 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity of follitropin alfa.

No teratogenic effect has been observed in animal studies (see section 5.3).

In case of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of GONAL-f.

Breastfeeding

GONAL-f is not indicated during breastfeeding.

Fertility

GONAL-f is indicated for use in infertility (see section 4.1).

4.7 Effects On Ability To Drive And Use Machines

GONAL-f is expected to have no or negligible influence on the ability to drive and use machines.

4.8 Undesirable Effects

The most commonly reported adverse reactions are headache, ovarian cysts and local injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection).

Mild or moderate ovarian hyperstimulation syndrome (OHSS) has been commonly reported and should be considered as an intrinsic risk of the stimulation procedure. Severe OHSS is uncommon (see section 4.4).

Thromboembolism may occur very rarely, usually associated with severe OHSS (see section 4.4).

The following definitions apply to the frequency terminology used hereafter:

Very common (

Common (

Uncommon (

Rare (

Very rare (< 1/10,000)

Treatment in women

Immune system disorders Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and shock Nervous system disorders Very common: Headache Vascular disorders Very rare: Thromboembolism, usually associated with severe OHSS (see section 4.4) Respiratory, thoracic and mediastinal disorders Very rare: Exacerbation or aggravation of asthma Gastrointestinal disorders Common: Abdominal pain, abdominal distension, abdominal discomfort, nausea, vomiting, diarrhoea Reproductive system and breast disorders Very common: Ovarian cysts Common: Mild or moderate OHSS (including associated symptomatology) Uncommon: Severe OHSS (including associated symptomatology) (see section 4.4) Rare: Complication of severe OHSS General disorders and administration site conditions Very common: Injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection)

Treatment in men

Immune system disorders Very rare: Mild to severe hypersensitivity reactions including anaphylactic reactions and shock Respiratory, thoracic and mediastinal disorders Very rare: Exacerbation or aggravation of asthma Skin and subcutaneous tissue disorders Common: Acne Reproductive system and breast disorders Common: Gynaecomastia, Varicocele General disorders and administration site conditions Very common: Injection site reactions (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection) Investigations Common: Weight gain 4.9 Overdose

The effects of an overdose of GONAL-f are unknown, nevertheless, there is a possibility that OHSS may occur (see section 4.4).

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Sex hormones and modulators of the genital systems, gonadotropins, ATC code: G03GA05.

In women, the most important effect resulting from parenteral administration of FSH is the development of mature Graafian follicles. In women with anovulation, the object of GONAL-f therapy is to develop a single mature Graafian follicle from which the ovum will be liberated after the administration of hCG.

Clinical efficacy and safety in women

In clinical trials, patients with severe FSH and LH deficiency were defined by an endogenous serum LH level < 1.2 IU/l as measured in a central laboratory. However, it should be taken into account that there are variations between LH measurements performed in different laboratories.

In clinical studies comparing r-hFSH (follitropin alfa) and urinary FSH in ART (see table below) and in ovulation induction, GONAL-f was more potent than urinary FSH in terms of a lower total dose and a shorter treatment period needed to trigger follicular maturation.

In ART, GONAL-f at a lower total dose and shorter treatment period than urinary FSH, resulted in a higher number of oocytes retrieved when compared to urinary FSH.

Table: Results of study GF 8407 (randomised parallel group study comparing efficacy and safety of GONAL-f with urinary FSH in assisted reproduction technologies)

GONAL-f

(n = 130)

urinary FSH

(n = 116)

Number of oocytes retrieved

11.0 ± 5.9

8.8 ± 4.8

Days of FSH stimulation required

11.7 ± 1.9

14.5 ± 3.3

Total dose of FSH required (number of FSH 75 IU ampoules)

27.6 ± 10.2

40.7 ± 13.6

Need to increase the dose (%)

56.2

85.3

Differences between the 2 groups were statistically significant (p< 0.05) for all criteria listed.

Clinical efficacy and safety in men

In men deficient in FSH, GONAL-f administered concomitantly with hCG for at least 4 months induces spermatogenesis.

5.2 Pharmacokinetic Properties

Following intravenous administration, follitropin alfa is distributed to the extracellular fluid space with an initial half-life of around 2 hours and eliminated from the body with a terminal half-life of about one day. The steady state volume of distribution and total clearance are 10 l and 0.6 l/h, respectively. One-eighth of the follitropin alfa dose is excreted in the urine.

Following subcutaneous administration, the absolute bioavailability is about 70 %. Following repeated administration, follitropin alfa accumulates 3-fold achieving a steady-state within 3-4 days. In women whose endogenous gonadotropin secretion is suppressed, follitropin alfa has nevertheless been shown to effectively stimulate follicular development and steroidogenesis, despite unmeasurable LH levels.

5.3 Preclinical Safety Data

Non-clinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity and genotoxicity additional to that already stated in other sections of this SmPC.

In rabbits, the formulation reconstituted with 0.9 % benzyl alcohol and 0.9 % benzyl alcohol alone, both resulted in a slight haemorrhage and subacute inflammation after single subcutaneous injection or mild inflammatory and degenerative changes after single intramuscular injection respectively.

Impaired fertility has been reported in rats exposed to pharmacological doses of follitropin alfa (

Given in high doses (

6. Pharmaceutical Particulars 6.1 List Of Excipients

Powder

Sucrose

Sodium dihydrogen phosphate monohydrate

Disodium phosphate dihydrate

Phosphoric acid, concentrated

Sodium hydroxide

Solvent

Water for injections

Benzyl alcohol

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

2 years.

The reconstituted solution is stable for 28 days at or below 25°C.

6.4 Special Precautions For Storage

Prior to reconstitution, do not store above 25°C. Store in the original package, in order to protect from light.

After reconstitution, do not store above 25°C. Do not freeze. Store in the original container, in order to protect from light.

6.5 Nature And Contents Of Container

GONAL f is presented as a powder and solvent for injection. The powder is presented in 3 ml vials (Type I glass), with rubber stopper (bromobutyl rubber) and aluminium flip-off cap. The solvent for reconstitution is presented in 2 ml pre-filled syringes (Type I glass) with a rubber stopper. The administration syringes made of polypropylene with a stainless steel pre-fixed needle are also provided.

The medicinal product is supplied as a pack of 1 vial of powder with 1 pre-filled syringe of solvent for reconstitution and 15 disposable syringes for administration graduated in FSH units.

6.6 Special Precautions For Disposal And Other Handling

GONAL-f 1050 IU/1.75 ml (77 micrograms/1.75 ml) must be reconstituted with the 2 ml solvent provided before use.

GONAL-f 1050 IU/1.75 ml (77 micrograms/1.75 ml) preparation must not be reconstituted with any other GONAL-f containers.

The solvent pre-filled syringe provided should be used for reconstitution only and then disposed of in accordance with local requirements. A set of administration syringes graduated in FSH units is supplied in the GONAL-f multidose box. Alternatively, a 1 ml syringe, graduated in ml, with pre-fixed needle for subcutaneous administration could be used (see section “How to prepare and use the GONAL-f powder and solvent” in the package leaflet).

The reconstituted solution should not be administered if it contains particles or is not clear.Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing Authorisation Holder

Merck Serono Europe Ltd.

56 Marsh Wall

London E14 9TP

United Kingdom

8. Marketing Authorisation Number(S)

EU/1/95/001/021

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 20 October 1995.

Date of last renewal: 20 October 2010.

10. Date Of Revision Of The Text

May 2011

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu

Follistim AQ Cartridge

Generic Name: follicle stimulating hormone (FOL ik al STIM ue lay ting HOR mone)
Brand Names: Follistim AQ, Follistim AQ Cartridge, Gonal-F, Gonal-f RFF, Gonal-f RFF Pen

What is Follistim AQ Cartridge (follicle stimulating hormone)?

Follicle stimulating hormone is a man-made form of a hormone that occurs naturally in the body. This hormone regulates ovulation, the growth and development of eggs in a woman's ovaries.

Follicle stimulating hormone is often used together with another medication called human chorionic gonadotropin (hCG).

Follicle stimulating hormone may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Follistim AQ Cartridge (follicle stimulating hormone)? Do not use this medication if you are already pregnant. Your doctor may give you a pregnancy test to make sure you are not pregnant before you receive follicle stimulating hormone.

Follicle stimulating hormone is not effective in women with primary ovarian failure or in men with primary testicular failure.

Before using follicle stimulating hormone, tell your doctor if you have polycystic ovary disease, asthma, or a history of stroke or blood clot.

What should I discuss with my healthcare provider before using Follistim AQ Cartridge (follicle stimulating hormone)?

This medication is not effective in women with primary ovarian failure (when the ovaries are unable to produce an egg).

This medication is not effective in men with primary testicular failure (when the testicles are unable to produce sperm).

You should not use follicle stimulating hormone if you are allergic to it, if you are already pregnant, or if you have:

an untreated or uncontrolled disorder of the thyroid, pituitary gland, or adrenal glands;

heavy or abnormal vaginal bleeding that has not been checked by a doctor;

an ovarian cyst;

cancer of the breast, ovary, uterus, testicle, hypothalamus, or pituitary gland; or

if you are allergic to neomycin (Mycifradin, Neo-Fradin) or streptomycin.

To make sure you can safely use follicle stimulating hormone, tell your doctor if you have:

polycystic ovary disease;

asthma; or

a history of stroke or blood clot.

It is not known whether follicle stimulating hormone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using follicle stimulating hormone. How should I use Follistim AQ Cartridge (follicle stimulating hormone)? You must remain under the care of a doctor while using follicle stimulating hormone.