Gonal-F SC Injection

Follitropin alfa 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 Follitropin Alfa, when monitoring of the patient indicates that sufficient follicular development is achieved. Follitropin Alfa stimulates spermatogenesis in men with hypogonadotropic hypogonadism when administered with hCG.

Induction of Ovulation-

• Initial starting dose of the first cycle-75 International Units of follitropin alfa 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)-

• 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-

• Use in conjunction with hCG.
• Prior to concomitant therapy with follitropin alfa 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 follitropin alfa 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.

Other ovulation stimulating agents (eg hCG, clomiphene citrate) may potentiate the follicular response, concurrent use of GnRH agonist-induced pituitary desensitisation may increase the dosage of Gonal-f needed to elicit an adequate ovarian response.

Follitropin Alfa is contraindicated in women and men who exhibit:

• 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

Follitropin Alfa is also contraindicated in women who exhibit:

• Abnormal uterine bleeding of undetermined origin
• Ovarian cyst or enlargement of undetermined origin.

The most common adverse reactions (≥5%) in ovulation induction include: ovarian cyst,headache, abdominal pain, OHSS, nausea, flatulence, pain and intermenstrual bleeding.

The most common adverse reactions (≥5%) in development of multiple follliclesg in ART include: headache, nausea, pelvic pain and abdominal pain.

The most common adverse reactions (>5%) in hypogonadotropic hypogonadal men participating in induction of spermatogenesis include: acne, injection site pain, fatigue, gynecomastia and seborrhea.

Follitropin Alfa 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 Follitropin Alfa alone or as part of IVF or ICSI cycles, increases the risk of congenital malformations.

There are no data on the presence of Follitropin Alfa 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 Follitropin Alfa.

Hypersensitivity Reactions and Anaphylaxis: If occurs, initiate appropriate therapy including supportive measures, and discontinue Gonal-F.

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.

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.

Ovarian Torsion: Early diagnosis and immediate detorsion limit damage to the ovary due to reduced blood supply.

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.

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.

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.

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.

Spontaneous Abortion: The risk of spontaneous abortion (miscarriage) is increased with gonadotropin products, however, causality has not been established.

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.

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

Geriatric Use: Safety and effectiveness of Gonal-F in postmenopausal women have not been established and it is not indicated in this population.

Drugs for Infertility

Lyophilized Multi-Dose vials may be stored refrigerated or at room temperature (2°-25°C).