FOLLISTIM AQ CARTRIDGE SIDE EFFECTS

SIDE EFFECTS

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

• Ovarian Hyperstimulation Syndrome
• Atelectasis
• Thromboembolism
• Ovarian Torsion
• Multi-fetal Gestation and Birth
• Congenital Anomalies
• Ectopic Pregnancy
• Spontaneous Abortion

Clinical Study Experience

Because clinical trials are conducted under widely varying conditions, adverse reactions 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.

Ovulation Induction

In a single cycle, multi-center, assessor-blind, parallel group, comparative study, a total of 172 chronic anovulatory women who had failed to ovulate and/or conceive with clomiphene citrate therapy, were randomized and treated with Follistim (105) or a urofollitropin comparator. Adverse reactions with an incidence of greater than 2% in either treatment group are listed in Table 1.

Table 1: Common Adverse Reactions Reported at a Frequency of ≥ 2% in an Assessor-Blind, Comparative Study of Anovulatory Women Receiving Ovulation Induction

Adverse reactions reported commonly (greater than or equal to 2% of women treated with Follistim) in other ovulation induction clinical trials were headache, abdominal distension, constipation, diarrhea, nausea, pelvic pain, uterine enlargement, vaginal hemorrhage and injection site reaction.

In Vitro Fertilization/Intracytoplasmic Sperm Injection

In a single cycle, multi-center, double-blind, parallel group, comparative study, a total of 1509 women were randomized to receive controlled ovarian stimulation with either Follistim AQ Cartridge (751 women were treated with Follistim AQ Cartridge) or a comparator and pituitary suppression with a gonadotropin releasing hormone (GnRH) antagonist as part of an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle. Table 2 lists adverse reactions with an incidence of greater than 2% in the group of women treated with Follistim AQ Cartridge.

Table 2: Common Adverse Reactions Reported At a Frequency of ≥ 2% in a Randomized, Double-blind, Active-controlled, Comparative Study of Normal Ovulatory Women Undergoing Controlled Ovarian Stimulation as Part of an In Vitro Fertilization or Intracytoplasmic Sperm Injection Cycle

Induction of Spermatogenesis

In an open-label, non-comparative clinical trial, 49 men with hypogonadotropic hypogonadism were enrolled to received pretreatment with hCG, followed by combination therapy with hCG and Follistim for induction of spermatogenesis. Of the 49 men, 30 received weekly Follistim doses of 450 international units; 24 of these 30 men received a total of 48 weeks of treatment with Follistim. Adverse reactions occurring with an incidence of greater than 2% in the 30 men treated with Follistim are listed in Table 3.

Table 3: Common Adverse Reactions Reported At a Frequency of ≥ 2% in an Open-Label Clinical Trial in Men with Hypogonadotropic Hypogonadism

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Follistim and/or Follistim AQ Cartridge. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal disorders

Abdominal distension, abdominal pain, constipation, diarrhea

General disorders and administration site conditions

Injection site reaction

Reproductive system and breast disorders

Breast tenderness, metrorrhagia, ovarian enlargement, vaginal hemorrhage

Skin and subcutaneous tissue disorders

Rash

Vascular disorders

Thromboembolism