Ospemifeneside effects

The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders Malignant Neoplasms The most common adverse reactions (≥1 percent) with OSPHENA are: hot flush, vaginal discharge, muscle spasms, headache, hyperhidrosis, vaginal hemorrhage, night sweats. To report SUSPECTED ADVERSE REACTIONS, contact Duchesnay Inc. at 1-855-OSPHENA (1-855-677-4362) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials 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 trials of another drug and may not reflect the rates observed in practice. The safety of OSPHENA has been assessed in ten phase 2/3 trials (N=2209) with doses ranging from 5 to 90 mg per day. The duration of treatment in these studies ranged from 6 weeks to 15 months. The majority of women (N=1683) had treatment exposure up to 12 weeks; 847 had up to 52 weeks (1 year) of exposure. The incidence rates of thromboembolic and hemorrhagic stroke were 1.13 per thousand women years (1 reported case of thromboembolic stroke) and 3.39 per thousand women years (3 reported cases of hemorrhagic stroke), respectively in OSPHENA 60 mg treatment group and 3.15 (1 case of thromboembolic stroke) and 0 per thousand women years, respectively in placebo. There were 2 reported cases of DVT among the 1459 women in the OSPHENA 60 mg treatment group and 1 case of DVT among the 1136 women in the placebo group. Table 1 lists adverse reactions occurring more frequently in the OSPHENA 60 mg treatment group than in placebo and at a frequency ≥1% in the 12-week, double-blind, placebo-controlled clinical trials. Table 2 lists adverse reactions occurring more frequently in the OSPHENA 60 mg treatment group than in placebo and at a frequency ≥1% in all clinical trials up to 52-weeks.

Table 1: Adverse Reactions Reported More Commonly in the OSPHENA Treatment Group (60 mg Once Daily) and at Frequency ≥1.0% in the 12 Week Double-Blind, Controlled Clinical Trials with OSPHENA vs. Placebo Ospemifene 60 mg (N=1459) % Placebo (N=1136) % Vascular Disorders Hot flush 6.5

2.6 Reproductive

System and Breast Disorders Vaginal discharge 3.8

0.4 Musculoskeletal and

Connective Tissue Disorders Muscle spasms 1.8

0.6 Skin and

Subcutaneous Tissue Disorders Hyperhidrosis 1.1

0.2 Table 2:

Adverse Reactions Reported More Commonly in the OSPHENA Treatment Group (60 mg Once Daily) and at Frequency ≥1.0% in All Clinical Trials up to 52 Weeks (Safety Population) Ospemifene 60 mg All Trials (N=847) % Placebo (N=165) % Nervous System Disorders Headaches 2.8

2.4 Vascular

Disorders Hot flush 12.2

4.2 Musculoskeletal and

Connective Tissue Disorders Muscle spasms 4.5

2.4 Skin and

Subcutaneous Tissue Disorders Hyperhidrosis 2.5 1.8 Night sweats 1.2

0.0 Reproductive

System and Breast Disorders Vaginal discharge 6.0 0.6 Vaginal hemorrhage 1.3 0.0

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of ospemifene. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neoplasms Benign, Malignant and Unspecified (incl. cysts and polyps): endometrial hyperplasia, endometrial cancer Immune System Disorders: allergic conditions including hypersensitivity, angioedema Nervous System Disorders: headache Vascular Disorders: deep vein thrombosis, thrombosis, pulmonary embolism Skin and Subcutaneous Tissue Disorders: rash, rash erythematous, rash generalized, pruritus, urticaria