Gonal-f

Q: Who makes Gonal-f?

Gonal-f is listed by 1 labeler in the FDA NDC directory, including EMD Serono, Inc..

follitropin alfa · Kit · Subcutaneous

Prescription (Rx)

Uses

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

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% benzyl alcohol), USP. Resulting concentration will be 600 International Units/mL. Following reconstitution as directed, product will deliver the equivalent of six 75 International Units doses. Multi-Dose 1050 International Units Vial: Dissolve the contents of one Multi-Dose vial (1050 International Units) with 2 mL Bacteriostatic Water for Injection (0.9% benzyl alcohol), USP. Resulting concentration will be 600 International Units/mL. Following reconstitution as directed, product will deliver the equivalent of fourteen 75 International Units doses. Discard unused reconstituted solution after 28 days. Administer GONAL-f subcutaneously in the abdomen, upper arm, or upper leg as described in Patient Information and Instructions for Use. Figure 2.3 Dosing for Ovulation Induction Prior to initiation of treatment with GONAL-f: Perform a complete gynecologic and endocrinologic evaluation Exclude primary ovarian failure Exclude the possibility of pregnancy Demonstrate tubal patency Evaluate the fertility status of the male partner The dosing scheme is stepwise and is individualized for each woman [see Clinical Studies (14.1) ]. Administer a starting dose of 75 International Units of GONAL-f subcutaneously daily for 14 days in the first cycle of use. In subsequent cycles of treatment, determine the starting dose (and dosage adjustments) of GONAL-f based on the woman's history of the ovarian response to GONAL-f. If indicated by the ovarian response after the initial 14 days, make an incremental adjustment in dose of up to 37.5 International Units. If indicated by the ovarian response, make additional incremental adjustments in the dose, up to 37.5 International Units, every 7 days. Continue treatment until follicular growth and/or serum estradiol levels indicate an adequate ovarian response. Consider the following when planning the woman's individualized dose: Use the lowest dose of GONAL-f consistent with the expectation of good results. Use appropriate GONAL-f dose adjustment(s) to prevent multiple follicular growth and cycle cancellation. The maximum, individualized, daily dose of GONAL-f is 300 International Units per day. In general, do not exceed 35 days of treatment, unless an estradiol rise indicates imminent follicular development. When pre-ovulatory conditions are reached, administer human chorionic gonadotropin (hCG) to induce final oocyte maturation and ovulation. Human chorionic gonadotropin, hCG, (5,000 USP units) should be given 1 day after the last dose of GONAL-f. Encourage the woman and her partner to have intercourse daily, beginning on the day prior to the administration of hCG and until ovulation becomes apparent. Withhold hCG in cases where the ovarian monitoring suggests an increased risk of ovarian hyperstimulation syndrome (OHSS) on the last day of GONAL-f therapy (for example estradiol greater than 2,000 pg per mL) [see Warnings and Precautions (5.2 , 5.3 , 5.5 , 5.11) ].

Dosage forms and strengths

For Injection: 450 International Units of white lyophilized powder in a multiple-dose vial For Injection: 1050 International Units of white lyophilized powder in a multiple-dose vial For Injection: 450 International Units in a multiple-dose vial.( 3 ) For Injection: 1050 International Units in a multiple-dose vial. ( 3 )

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

Warnings and precautions

Hypersensitivity Reactions and Anaphylaxis: If occurs, initiate appropriate therapy including supportive measures, and discontinue GONAL-f ( 5.1 ) Ovarian Hyperstimulation Syndrome: If serious, stop gonadotropins, including hCG, and determine if the woman needs to be hospitalized. Treatment is primarily symptomatic and consists of bed rest, fluid and electrolyte management, and analgesics ( 5.2 ) Pulmonary and Vascular Complications: In women with recognized risk factors, the benefits of induction of ovulation and ART need to be weighed against the risks. During or after use of GONAL-f, monitor for venous or arterial thromboembolic events ( 5.3 ) Ovarian Torsion: Early diagnosis and immediate detorsion limit damage to the ovary due to reduced blood supply ( 5.4 ) Abnormal Ovarian Enlargement: If the ovaries are abnormally enlarged on the last day of GONAL-f therapy, inform women not to administer hCG and to avoid intercourse ( 5.5 ) Multi-fetal Gestation and Births: The rate of multiple births is dependent on the number of embryos transferred. Advise the woman and her partner of the potential risk of multi-fetal gestation and birth before beginning therapy with GONAL-f ( 5.6 ) Embryofetal Toxicity: Inform women that the incidence of congenital malformations (birth defects) after some Assisted Reproductive Technology (ART) [specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)] may be slightly higher than after spontaneous conception. There is no evidence that the use of gonadotropins during IVF or ICSI is associated with an increased risk of congenital malformations ( 5.7 ) Ectopic Pregnancy: Advise women who become pregnant following ART and have: abdominal/pelvic pain (particularly on one side); shoulder, neck or rectal pain; and nausea and vomiting to seek immediate medical attention. Confirm the presence of an intrauterine pregnancy early by β-hCG testing and transvaginal ultrasound ( 5.8 ) Spontaneous Abortion: The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products, however, causality has not been established ( 5.9 ) Ovarian Neoplasm: Both benign and malignant ovarian neoplasms are reported in women who have had multiple drug therapy for controlled ovarian stimulation, however, causality has not been established ( 5.10 ) 5.1 Hypersensitivity Reactions and Anaphylaxis In the post-marketing experience, serious systemic hypersensitivity reactions, including anaphylaxis, have been reported with use of GONAL-f and GONAL-f RFF. Symptoms have included dyspnea, facial edema, pruritus, and urticaria. If an anaphylactic or other serious allergic reaction occurs, initiate appropriate therapy including supportive measures if cardiovascular instability and/or respiratory compromise occur, and discontinue further use. 5.2 Ovarian Hyperstimulation Syndrome (OHSS) Ovarian Hyperstimulation Syndrome (OHSS) is a medical entity distinct from uncomplicated ovarian enlargement and may progress rapidly to become a serious medical event. OHSS is characterized by a dramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. The early warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain. Abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement [see Warnings and Precautions (5.6) ] , weight gain, dyspnea, and oliguria have been reported with OHSS. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic reactions [see Warnings and Precautions (5.4) ] . Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy, have been reported in association with OHSS. OHSS occurs after gonadotropin treatment has been discontinued and it can develop rapidly, reaching its maximum about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration [see Dosage and Administration (2.2 , 2.3) ] , withhold hCG. Cases of OHSS are more common, more severe, and more protracted if pregnancy occurs; therefore, assess women for the development of OHSS for at least two weeks after hCG administration. If serious OHSS occurs, stop gonadotropins, including GONAL-f and hCG, and consider whether the woman needs to be hospitalized. Treatment is primarily symptomatic and overall consists of bed rest, fluid and electrolyte management, and analgesics (if needed). Because the use of diuretics can accentuate the diminished intravascular volume, avoid diuretics except in the late phase of resolution as described below. The management of OHSS is divided into three phases as follows: Acute Phase : Management is directed at preventing hemoconcentration due to loss of intravascular volume to the third space and minimizing the risk of thromboembolic phenomena and kidney damage. Thoroughly assess daily or more often, based on the clinical need, fluid intake and output, weight, hematocrit, serum and urinary electrolytes, urine specific gravity, BUN and creatinine, total proteins with albumin: globulin ratio, coagulation studies, electrocardiogram to monitor for hyperkalemia, and abdominal girth. Treatment, consisting of limited intravenous fluids, electrolytes, human serum albumin, is intended to normalize electrolytes while maintaining an acceptable but somewhat reduced intravascular volume. Full correction of the intravascular volume deficit may lead to an unacceptable increase in the amount of third space fluid accumulation.

Side effects

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 hypogonadism was examined in 3 open-label, non-randomized, multi-center, multi-national, escalating dose clinical trials (Trials 1, 2 and 3) conducted in 76 adult men (aged 16 to 48 years) with primary or secondary hypogonadotropic hypogonadism (defined as serum testosterone <100 ng/mL and low or normal FSH and LH) and azoospermia (sperm concentration <0.1×10 6 /mL). Of the 76 men enrolled, 63 received treatment with GONAL-f. During these trials, there was one serious adverse reaction of gynecomastia requiring surgical excision of breast tissue in a 50 year old man who received 9 months of therapy with GONAL-f. Pathology report showed gynecomastia with no atypia. There were no discontinuations due to adverse reactions. Adverse reactions reported in Trials 1, 2 and 3 by ≥2 patients during treatment with GONAL-f are shown in Table 3. Table 3. Common Adverse Reactions in Men with Azoospermia and Primary or Secondary Hypogonadotropic Hypogonadism Receiving GONAL-f in Trials 1, 2 and 3 for Induction for Spermatogenesis N=63 n (%) Acne 17 (27) Injection site pain 7 (11) Gynecomastia 4 (6) Seborrhea 3 (5) Fatigue 6 (10) Libido decreased 2 (3) 6.2 Postmarketing Experience In addition to adverse events reported from clinical trials, the following adverse reactions have been reported during postmarketing use of GONAL-f. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to GONAL-f cannot be reliably determined. Body as a Whole - General: Hypersensitivity reactions including anaphylaxis Respiratory System: Asthma exacerbation Vascular Disorders: Thromboembolism

Use in specific populations

Lactation: Advise not to breastfeed ( 8.2 ) 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 rats, where dosing occurred from mid-gestation through lactation, showed difficult and prolonged parturition in all dams dosed at 41 times the lowest clinical dose of 75 International Units based on body surface area, along with maternal death and stillborn pups associated with the difficult and prolonged parturition. This toxicity was not observed in dams and offspring dosed at a level 5 times the lowest clinical dose of 75 International Units based on body surface area. 8.2 Lactation There are no data on the presence of GONAL-f in human milk, the effects on the breastfed infant, or the effects on milk production. Because the secretion of prolactin during lactation can result in inadequate response to ovarian stimulation, advise women not to breast feed during treatment with GONAL-f. 8.3 Females and Males of Reproductive Potential Because GONAL-f is not indicated in pregnant women, verify a negative pregnancy test before administering GONAL-f to a woman [see Dosage and Administration (2.3 , 2.4) ]. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Safety and effectiveness of GONAL-f in postmenopausal women have not been established and it is not indicated in this population.

Pregnancy

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 rats, where dosing occurred from mid-gestation through lactation, showed difficult and prolonged parturition in all dams dosed at 41 times the lowest clinical dose of 75 International Units based on body surface area, along with maternal death and stillborn pups associated with the difficult and prolonged parturition. This toxicity was not observed in dams and offspring dosed at a level 5 times the lowest clinical dose of 75 International Units based on body surface area.

Pediatric use

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Safety and effectiveness of GONAL-f in postmenopausal women have not been established and it is not indicated in this population.

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) ].

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.

Mechanism of action

12.1 Mechanism of Action GONAL-f stimulates ovarian follicular growth in women who do not have primary ovarian failure. In order to bring about final maturation of the follicle and ovulation in the absence of an endogenous LH surge, human chorionic gonadotropin (hCG) must be given, following the administration of GONAL-f, when monitoring of the patient indicates that sufficient follicular development is achieved. GONAL-f stimulates spermatogenesis in men with hypogonadotropic hypogonadism when administered with hCG.

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) ] .

Storage

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) ] .

Patient information

Advise women and men to read the FDA-approved patient labeling (Patient Information and Instructions for Use) Hypersensitivity Reactions and Anaphylaxis Advise women and men to discontinue GONAL-f and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur [see Warnings and Precautions (5.1) ]. Ovarian Hyperstimulation Syndrome Inform women regarding the risks of OHSS [see Warnings and Precautions (5.2 ] and OHSS-associated conditions including pulmonary and vascular complications [see Warnings and Precautions (5.3) ] and ovarian torsion [see Warnings and Precautions (5.4) ] with the use of GONAL-f. Advise women to seek medical attention if any of these conditions occur. Abnormal Ovarian Enlargement Inform women regarding the hazards associated with abnormal ovarian enlargement that may occur with GONAL-f therapy. If the ovaries are abnormally enlarged on the last day of GONAL-f therapy, inform women not to administer hCG and to avoid intercourse [see Warnings and Precautions (5.5) ] . Multi-fetal Gestation and Birth Advise the woman and her partner of the potential risk of multi-fetal gestation and birth before beginning therapy with GONAL-f [see Warnings and Precautions (5.6) ]. Embryofetal Toxicity Inform women that the incidence of congenital malformations (birth defects) after some Assisted Reproductive Technology [(ART) specifically in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)] may be slightly higher than after spontaneous conception [see Warnings and Precautions (5.7) ] . Ectopic Pregnancy Inform women undergoing ART that the incidence of ectopic pregnancy may be increased with these procedures, particularly for women with tubal abnormalities. Advise women who become pregnant and have: abdominal/pelvic pain (particularly on one side); shoulder, neck or rectal pain; and nausea and vomiting to seek immediate medical attention [see Warnings and Precautions (5.8) ] . Spontaneous Abortion Inform women that the risk of spontaneous abortion (miscarriage) is increased with gonadotropin products (including GONAL-f). However, causality has not been established. The increased risk may be a factor of the underlying infertility [see Warnings and Precautions (5.9) ] . Lactation Advise women not to breastfeed because the secretion of prolactin during lactation can result in inadequate response to ovarian stimulation with GONAL-f [see Use in Specific Populations (8.2) ] . Dosing and Use of GONAL-f Multi Dose Instruct women and men on the correct usage and dosing of GONAL-f [see Dosage and Administration (2.3 , 2.4 , 2.5) ] . Caution against changing the dosage or the schedule of administration unless instructed to do so by a healthcare provider. Duration and Necessary Monitoring in Patients Undergoing Therapy with GONAL-f Prior to beginning therapy with GONAL-f, inform women and men about the time commitment and monitoring procedures necessary for treatment [see Dosage and Administration (2.3 , 2.4 , 2.5) and Warnings and Precautions (5.11) ]. Instructions Regarding a Missed Dose Inform women and men that if they miss or forget to take a dose of GONAL-f, they should not double the next dose and should call their healthcare provider for further dosing instructions.

Label text from the FDA structured product label by EMD Serono, Inc. (revised Sep 2, 2025). Long sections are shortened; the complete label is on DailyMed.

Gonal-f NDC products (1)

NDC	Strength & form	Labeler	Type
44087-9030	Kit	EMD Serono, Inc.	BLA

Frequently asked questions

What is Gonal-f used for?

What are the side effects of Gonal-f?

Who makes Gonal-f?

Gonal-f is listed by 1 labeler in the FDA NDC directory, including EMD Serono, Inc..