Follicleside effects

The following serious adverse reactions are discussed elsewhere in the labeling: Abnormal Ovarian Enlargement Ovarian Hyperstimulation Syndrome Atelectasis, acute respiratory distress syndrome and exacerbation of asthma Thromboembolic events Ovarian Torsion Multi-fetal Gestation and Birth Congenital Malformations Ectopic Pregnancy Spontaneous Abortion Ovarian Neoplasms The most common adverse reactions (≥2%) in ART include: abdominal cramps; abdomen enlarged; abdominal pain; headache; injection site pain and reaction; injection site inflammation; OHSS To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trial 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. In two single cycle, open label, multinational, multicenter, comparative trials, a total of 434 normal ovulatory infertile women were randomized and received subcutaneously administered MENOPUR as part of an in vitro fertilization (IVF) cycle (both trials) or intracytoplasmic sperm injection (ICSI) cycle (one of the two trials). All women received pituitary down-regulation with gonadotropin releasing hormone (GnRH) agonist before stimulation. Adverse Reactions occurring at an incidence of ≥ 2% in women receiving MENOPUR are shown in Table 1.

Table 1: MENOPUR Administered Subcutaneously in Women Undergoing IVF and ICSI. Adverse Reactions with Incidence of 2% or Greater Occurring on or After GnRH Administration. Body System/Preferred Term IVF n=434 N % Body as a whole Abdominal cramps 13 3.0 Abdomen enlarged 10 2.3 Abdominal pain 29 6.7 Headache 27 6.2 Injection site pain + reaction 17 3.9 Injection site inflammation 10

2.3 Urogenital

Ovarian Hyperstimulation Syndrome (OHSS) 27 6.2 In addition, thrombophlebitis was reported in less than 1% of subjects. In an open label, US, multicenter, comparative IVF and ICSI trial, MENOPUR and BRAVELLE were administered in the same syringe to 60 normal ovulatory infertile women. OHSS, post retrieval cramping and nausea and spontaneous abortion were the most common adverse reactions occurring at an incidence of ≥ 5% in women receiving the combination of MENOPUR and BRAVELLE. In another open label, US multicenter, comparative trial for ovulation induction in anovulatory or oligovulatory infertile women, 76 subjects received subcutaneous or intramuscular injections of MENOPUR. The most common adverse reactions occurring at an incidence of ≥ 5% in women receiving MENOPUR were: headache; OHSS; injection site reaction, abdominal cramps, fullness and pain; and nausea.

6.2 Postmarketing

Experience The following adverse reactions have been reported during postmarketing use of gonadotropins. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to MENOPUR cannot be reliably determined.

Gastrointestinal disorders: abdominal pain, abdominal pain lower, abdominal distension, nausea, vomiting, abdominal discomfort General disorders and administration site conditions: injection site reactions (most frequently reported injection site reaction was injection site pain), fatigue Nervous system disorders: headache, dizziness Reproductive system disorders: OHSS, pelvic pain, ovarian cyst, breast complaints (including breast pain, breast tenderness, breast discomfort, and breast swelling) Skin and subcutaneous tissue disorders: acne, rash Vascular disorders: hot flush