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Follitropin Alfa

FDA Drug Information • Also known as: Gonal-F

Brand Names
Gonal-F
Route
SUBCUTANEOUS
Dosage Form
KIT
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Follitropin alfa, a gonadotropin [human follicle stimulating hormone (hFSH)], is a glycoprotein hormone produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) cell line. It has a dimeric structure containing two glycoprotein subunits (alpha and beta). The alpha and beta subunits have 92 and 111 amino acids, respectively, and their primary and tertiary structures are indistinguishable from those of human follicle stimulating hormone. The molecular weight is approximately 31 kDa (14 kDa for alpha subunit and 17 kDa for beta subunit). GONAL-f (follitropin alfa) for injection is a sterile, lyophilized powder intended for subcutaneous injection after reconstitution. Each multiple-dose vial of GONAL-f containing either 450 International Units (33 mcg) or 1050 International Units (77 mcg) follitropin alfa and the inactive ingredients dibasic sodium phosphate (0.89 mg), monobasic sodium phosphate (0.39 mg), and sucrose (30 mg). Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment. After reconstitution with supplied 1 mL of with Bacteriostatic Water for Injection (0.9% benzyl alcohol), USP, the resultant concentration is 600 IU/mL with a pH of approximately 6.5 to 7.5. Under current storage conditions, GONAL-f may contain up to 10% of oxidized follitropin alfa.

What Is Follitropin Alfa Used For?

1 INDICATIONS AND USAGE GONAL-f is indicated for: GONAL-f is a gonadotropin indicated for: Women: Induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure. ( 1.1 ) Development of multiple follicles in ovulatory infertile women as part of Assisted Reproductive Technology (ART) cycles. ( 1.2 ) Men: Induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism for whom the cause of infertility is not due to primary testicular failure. ( 1.3 ) 1.1 Induction of ovulation and pregnancy in oligo-anovulatory infertile women for whom the cause of infertility is functional and not due to primary ovarian failure. 1.2 Development of multiple follicles in ovulatory infertile women as part of an assisted reproductive technology (ART) cycle. 1.3 Induction of spermatogenesis in infertile men with primary and secondary hypogonadotropic hypogonadism for whom the cause of infertility is not due to primary testicular failure.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Induction of Ovulation ( 2.3 ) Initial starting dose of the first cycle - 75 International Units of GONAL-f per day for 14 days, administered subcutaneously Individualize doses after 14 days Do not administer doses greater than 300 International Units per day Development of Multiple Follicles in Assisted Reproductive Technology (ART) ( 2.3 ) Initial starting dose of the first cycle - 150 International Units per day, administered subcutaneously Dosage adjustments after 3 to 5 days and by 75 to 150 International Units at each adjustment Do not administer doses greater than 450 International Units per day Males with Hypogonadotropic Hypogonadism and Azoospermia ( 2.4 ) Use in conjunction with hCG. Prior to concomitant therapy with GONAL-f and hCG, pretreat with 1,000 to 2,250 USP units of hCG alone two to three times per week to achieve normal serum testosterone levels, which may take 3 to 6 months. After normalization of serum testosterone, administer 150 International Units of GONAL-f subcutaneously three times a week and 1,000 USP units of hCG (or the dose required to maintain serum testosterone levels within the normal range) three times a week. 2.1 Important Dosage and Administration Information Only physicians who are experienced in infertility treatment, should treat women with GONAL-f. GONAL-f is a gonadotropin product capable of causing in women, Ovarian Hyperstimulation Syndrome (OHSS) with or without pulmonary or vascular complications [see Warnings and Precautions (5.2 , 5.3) ] and multiple births [see Warnings and Precautions (5.6) ] . Gonadotropin therapy requires the availability of appropriate monitoring facilities [see Warnings and Precautions (5.11) ] . Use the lowest effective dose of GONAL-f. Give careful attention to the diagnosis of infertility and the selection of candidates for GONAL-f therapy [see Dosage and Administration (2.3 , 2.4) ] . 2.2 Preparation of GONAL-f and Selection of Injection Site Store lyophilized multiple-dose vials refrigerated or at room temperature (2°-25°C /36°-77°F) and protected from light. Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit. Instruct women and men to use the accompanying syringes, calibrated in International Units FSH for administration. The 27-gauge injection syringe (see figure below) has unit dose markings from 37.5 International Units to 600 International Units FSH for use with GONAL-f Multi-Dose. Instruct women and men to take a specific dose of GONAL-f Multi-Dose. Show women and men how to locate the syringe marking that corresponds to the prescribed dose. Each GONAL‑f Multi‑Dose Vial delivers 450 International Units or 1050 International Units of follitropin alfa, respectively Multi-Dose 450 International Units Vial: Dissolve the contents of one Multi-Dose vial (450 International Units) with 1 mL Bacteriostatic Water for Injection (0.9%...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Hypersensitivity Reactions and Anaphylaxis [see Warnings and Precautions (5.1) ] Ovarian Hyperstimulation Syndrome [see Warnings and Precautions (5.2) ] Pulmonary and Vascular Complication [see Warnings and Precautions (5.3) ] Ovarian Torsion [see Warnings and Precautions (5.4) ] Abnormal Ovarian Enlargement [see Warnings and Precautions (5.5) ] Multi-fetal Gestation and Birth [see Warnings and Precautions (5.6) ] Embryofetal Toxicity [see Warnings and Precautions (5.7) ] Ectopic Pregnancy [see Warnings and Precautions (5.8) ] Spontaneous Abortion [see Warnings and Precautions (5.9) ] Ovarian Neoplasms [see Warnings and Precautions (5.10) ] The most common adverse reactions (≥5%) in ovulation induction include: ovarian cyst, headache, abdominal pain, OHSS, nausea, flatulence, pain and intermenstrual bleeding. ( 6.1 ) The most common adverse reactions (≥5%) in development of multiple follicles in ART include: headache, nausea, pelvic pain and abdominal pain. ( 6.1 ) The most common adverse reactions (>5%) in hypogonadotropic hypogonadal men participating in induction of spermatogenesis include: acne, injection site pain, fatigue, gynecomastia and seborrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088, Ext 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Study Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. Women: The safety of GONAL-f was examined in four clinical trials that enrolled 691 women [two trials for ovulation induction (454 women) and two trials for ART (237 women)]. Induction of Ovulation In a randomized, open-labeled, multicenter, active-controlled trial in oligo-anovulatory infertile women, conducted in the U.S., a total of 118 oligo-anovulatory infertile women were randomized to and underwent ovulation induction with GONAL-f versus a comparator urofollitropin. Adverse reactions occurring in at least 5.0% of women receiving GONAL-f are listed in Table 1. Table 1: Common Adverse Reactions Reported at a Frequency of ≥ 5% in an U.S. Ovulation Induction Trial System Organ Class/Adverse Reactions GONAL-f N=118 total number of women treated with GONAL-f (288 treatment cycles up to 3 treatment cycles per woman ) n number of women with the adverse reaction (%) Body as a Whole - General Pain 6 (5.1%) Central and Peripheral Nervous System Headache 12 (10.2%) Gastrointestinal System Abdominal Pain 9 (7.6%) Nausea 7 (5.9%) Flatulence 7 (5.9%) Reproductive, Female Intermenstrual Bleeding 6 (5.1) Ovarian Hyperstimulation 8 (6.8%) Ovarian Cyst 17 (14.4%) Development of Multiple Follicles as part of an Assisted Reproductive Technology (ART) Cycle In a randomized, open-labeled, active-comparator trial conducted in the U.S., a total of 56 normal ovulatory infertile women were randomized and received GONAL-f versus a urofollitropin comparator as part of an ART [in vitro fertilization (IVF) or intracytoplasmic sperm injection cycle (ICSI)] cycle. All women received pituitary down-regulation with gonadotropin releasing hormone (GnRH) agonist before stimulation. Adverse Reactions occurring in at least 5.0% of women are listed in Table 2. Table 2: Common Adverse Reactions Reported at a Frequency of ≥ 5% in an U.S. ART Trial System Organ Class/Adverse Reactions GONAL-f (N=56 total number of women treated with GONAL-f ) n number of women with the adverse reaction (%) Central and Peripheral Nervous System Headache 7 (12.5%) Gastrointestinal System Abdominal Pain 3 (5.4%) Nausea 4 (7.1%) Reproductive, Female Pelvic Pain 4 (7.1) Induction of Spermatogenesis: The safety of GONAL-f for induction of spermatogenesis in men with primary or secondary hypogonadotropic...

Contraindications

4 CONTRAINDICATIONS GONAL-f is contraindicated in women and men who exhibit: Prior hypersensitivity to recombinant FSH products or one of their excipients. Reactions have included anaphylaxis [see Warning and Precautions (5.1) ] High levels of FSH indicating primary gonadal failure The presence of uncontrolled non-gonadal endocrinopathies (for example, thyroid, adrenal, or pituitary disorders) Sex hormone dependent tumors of the reproductive tract and accessory organs Tumors of pituitary gland or hypothalamus GONAL-f is also contraindicated in women who exhibit: Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin GONAL-f is contraindicated in women and men who exhibit ( 4 ): Prior hypersensitivity to recombinant FSH products or one of their excipients High levels of FSH indicating primary gonadal failure Uncontrolled non-gonadal endocrinopathies Sex hormone dependent tumors of the reproductive tract and accessory organs Tumors of pituitary gland or hypothalamus GONAL-f is also contraindicated in women who exhibit ( 4 ): Abnormal uterine bleeding of undetermined origin Ovarian cyst or enlargement of undetermined origin

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary GONAL-f is not indicated in pregnant women. The incidence of congenital malformations after some Assisted Reproductive Technology, specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), may be slightly higher than that after spontaneous conception. This slightly higher incidence is thought to be related to differences in parental characteristics (e.g., maternal age, maternal and paternal genetic background, sperm characteristics) and to a higher incidence of multi-fetal gestations after IVF or ICSI. There is no human data that the use of gonadotropins (including GONAL-f) alone or as part of IVF or ICSI cycles, increases the risk of congenital malformations. The risk of spontaneous abortion (miscarriage) is increased in women who have used gonadotropin products (including GONAL-f) to achieve pregnancy. In animal studies, the continuous administration of recombinant human FSH during pregnancy resulted in a decrease in the number of viable fetuses and difficult and prolonged delivery. No teratogenic effect has been observed. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Data on a limited number of exposed pregnancies indicate no adverse reactions of gonadotropins on pregnancy, embryonal or fetal development, parturition or postnatal development following controlled ovarian stimulation. Animal Data Embryofetal development studies with recombinant human FSH in rats, where dosing occurred during organogenesis, showed a dose dependent increase in difficult and prolonged parturition in dams, and dose dependent increases in resorptions, pre- and post-implantation losses, and stillborn pups at doses representing 5 and 41 times the lowest clinical dose of 75 International Units based on body surface area. Pre-/post-natal development studies with recombinant human FSH in...

Overdosage

10 OVERDOSAGE Ovarian hyperstimulation syndrome (OHSS) and multiple gestations have been observed in women with GONAL-f overdosage [see Warnings and Precautions (5.2 , 5.6) ].

How Supplied

16 How Supplied/Storage and Handling 16.1 How Supplied GONAL-f (follitropin alfa) for injection is supplied as a sterile, white lyophilized powder in multiple-dose vials of either 450 International Units per vial or 1050 International Units per vial. The following package presentations are available: NDC 44087-9030-1 - One multiple-dose vial of GONAL-f 450 International Units, one-1 mL prefilled diluent syringe of Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol), and six administration syringes calibrated in FSH Units (IU FSH) with a fixed 27-gauge × 0.5-inch needle. NDC 44087-9070-1 - One multiple-dose vial GONAL-f of 1050 International Units, one-2 mL prefilled diluent syringe of Bacteriostatic Water for Injection, USP (0.9% benzyl alcohol), and ten administration syringes calibrated in FSH Units (IU FSH) with a fixed 27-gauge × 0.5-inch needle. 16.2 Storage and Handling Store vials refrigerated between 2°C to 8°C (36°F to 46°F) or at room temperature between 20°C to 25°C (68°F to 77°F). Store reconstituted solution refrigerated between 2°C to 8°C (36°F to 46°F) or at room temperature between 20°C to 25°C (68°F to 77°F) and discard unused portion after 28 days. Protect from light [see Dosage and Administration (2.2) ] .

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.