GONAL-F SIDE EFFECTS

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

• Hypersensitivity Reactions and Anaphylaxis
• Ovarian Hyperstimulation Syndrome
• Pulmonary and Vascular Complication
• Ovarian Torsion
• Abnormal Ovarian Enlargement
• Multi-fetal Gestation and Birth
• Embryofetal Toxicity
• Ectopic Pregnancy
• Spontaneous Abortion
• Ovarian Neoplasms

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

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

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 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 <0.1×10⁶/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 orSecondary Hypogonadotropic Hypogonadism Receiving Gonal-F in Trials 1, 2 and 3 for Induction for Spermatogensis

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

SRC: NLM .