Important Safety Information including Boxed Warning and Indication

Important Safety Information for Osphena®

WARNING: Endometrial Cancer and Cardiovascular Disorders

Osphena® is an estrogen agonist/antagonist with tissue selective effects. In the endometrium Osphena® has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogen therapy. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

The Women’s Health Initiative (WHI) estrogen-alone sub study reported an increased risk of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg], relative to placebo. Osphena® 60 mg had thromboembolic and hemorrhagic stroke incidence rates of 0.72 and 1.45 per thousand women vs. 1.04 and 0 per thousand women for placebo and a DVT incidence rate of 1.45 vs. 1.04 per thousand women for placebo. Osphena® should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.

Contraindications

  • Undiagnosed abnormal genital bleeding
  • Known or suspected estrogen-dependent neoplasia
  • Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions
  • Active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions
  • Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to Osphena® or any of its ingredients
  • Women who are or may become pregnant. Osphena® may cause fetal harm when administered to a pregnant woman. Ospemifene was embryo-fetal lethal with labor difficulties and increased pup deaths in rats at doses below clinical exposures, and embryo-fetal lethal in rabbits at 10 times the clinical exposure based on mg/m2. If this drug is used during pregnancy, or if a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus.

Warnings and Precautions

In Osphena® clinical trials of up to 15 months, the incidence rates compared to placebo for thromboembolic and hemorrhagic stroke were 0.72 Osphena® 60 mg vs. 1.04 placebo and 1.45 Osphena® 60 mg vs. 0 placebo per thousand women. Should thromboembolic or hemorrhagic stroke occur or be suspected, Osphena® should be discontinued immediately. In clinical trials, a single MI occurred in a woman receiving Osphena® 60 mg.

Incidence rate of DVT was 1.45 Osphena® vs. 1.04 placebo per thousand women. Should a VTE occur or be suspected, Osphena® should be discontinued immediately. Osphena® should be discontinued at least 4 to 6 weeks before surgery with increased risk of thromboembolism or during periods of prolonged immobilization.

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogen therapy. The risk appears dependent on duration of treatment and estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. However, studies suggest a possible increased risk for breast cancer in patients receiving estrogen plus progestin therapy.

Osphena® is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, Osphena® has agonistic effects. In Osphena® clinical trials, no cases of endometrial cancer were seen with exposure up to 52 weeks. There was a single case of simple hyperplasia without atypia. Endometrial thickening equal to 5mm or greater was reported at a rate of 60.1 Osphena® vs. 21.2 placebo per 1000 women. Uterine polyps occurred at an incidence of 5.9 Osphena® vs. 1.8 placebo per 1000 women, and any type of proliferative endometrium (weakly plus active plus disordered) was 86.1 Osphena® vs. 13.3 placebo per 1000 women.

Osphena® has not been adequately studied in women with breast cancer; therefore it should not be used in women with known or suspected breast cancer or with a history of breast cancer.

Osphena® should not be used in women with severe hepatic impairment as it has not been studied.

In clinical trials the more commonly reported adverse reactions in ≥1 percent of patients treated with Osphena® 60 mg compared to placebo were: hot flush (7.5% vs. 2.6%), vaginal discharge (3.8% vs. 0.3%), muscle spasms (3.2% vs. 0.9%), hyperhidrosis (1.6% vs. 0.6%), and genital discharge (1.3% vs. 0.1%).

The following adverse reactions have been identified during post-approval use of ospemifene:

Immune System Disorders: allergic conditions including hypersensitivity, angioedema.
Nervous System Disorders: headache
Skin and Subcutaneous Tissue Disorders: rash, rash erythematous, rash generalized, pruritus, urticaria.

Drug interactions: Do not use estrogens or estrogen agonists/antagonists, fluconazole, or rifampin concomitantly with Osphena®. Co-administration of Osphena® with drugs that inhibit CYP3A4 and CYP2C9 may increase the risk of Osphena®-related adverse reactions. Osphena® is highly protein bound. Use cautiously with highly protein bound drugs as use with other highly protein-bound drugs may lead to increase exposure of that drug or ospemifene.

Please click for U.S. Full Prescribing Information for Osphena® (ospemifene) tablets, including Boxed Warning, and Patient Information.

Indication:

Osphena® (ospemifene) is indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

For U.S. Healthcare Professionals Only

How Osphena® Helps

Starting the conversation with your postmenopausal patients: patient profiles

Dyspareunia is a common condition, but every patient's preference is unique.1-4

Audrey

Audrey worries that vaginal creams and gels may be a barrier to sexual spontaneity.1-4

Karen

Karen is uncomfortable with the feeling left by vaginal creams and gels.1-4

Valerie

Valerie prefers taking a once-daily oral pill.1,4

Ava

Ava wants a hormone-free treatment option.1-4

Judy

Judy prefers a treatment that does not require vaginal insertion of an applicator.1-4

Note: Although patient preference should be considered, HCPs must determine appropriate treatment for individual patients based on medical history and current condition, as well as on the potential side effects of individual treatment options.

Help them start to enjoy sexual intimacy again with Osphena®

  • Once-daily oral pill taken with a full meal5
    • Taken with food: increases bioavailability 2 to 3-fold
      • In a cross study comparison, Osphena 60 mg was administered with an 860 kcal meal
  • Helps improve the specific vaginal tissue that causes pain5
    • Increases superficial cells, decreases parabasal cells and reduces vaginal pH5
  • Provides relief of moderate to severe dyspareunia in as little as 12 weeks5-7
  • Hormone free5,6,8
  • Level A treatment recommended by ACOG and NAMS7,8 based on its safety and efficacy profile

Common side effects may include hot flashes, vaginal discharge, muscle spasms and increased sweating.

Osphena should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.

Left untreated, dyspareunia may worsen1

Please see Important Safety Information and Full Prescribing Information, including Boxed Warning regarding Endometrial Cancer and Cardiovascular Disorders.

1 Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and Vaginal Atrophy in Postmenopausal Women: Findings from the REVIVE (REal Women’s Views of Treatment Options for Menopausal Vaginal ChangEs) Survey. J Sex Med 2013 Jul; 10: 1790-1799.

2 Krychman M, Graham S, Bernick B, et al. The Women’s EMPOWER Survey: Women’s Knowledge and Awareness of Treatment Options for Vulvar and Vaginal Atrophy Remains Inadequate. J Sex Med 2017;14:425e433.

3 Kingsberg S, Krychman M, Graham S, et al. The Women’s EMPOWER Survey: Identifying Women’s Perceptions on Vulvar and Vaginal Atrophy and Its Treatment. J Sex Med 2017;14:413e424.

4 Wysocki S, Kingsberg S, Krychman M. Management of Vaginal Atrophy: Implications from the REVIVE Survey. Clinical Medicine Insights Reproductive Health. 2014;8:23-30. doi:10.4137 CMRH.S14498.

5 Osphena® Package Insert. Florham Park, NJ: Shionogi Inc.; 2015.

6 Wurz G, Kao CJ, DeGregorio MA. Safety and efficacy of Ospemifene for the Treatment of Dyspareunia Associated with Vulvar and Vaginal Atrophy Due to Menopause. Clinical Interventions in Aging, 2014: 9 1939-1950.

7 ACOG Practice Bullet Number 141: Management of menopausal symptoms. Practice Bulletin No. 141. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2014:123(1):202-216

8 North American Menopause Society. Management of symptomatic vulvovaginal atrophy: 2013 position statement of the North American Menopause Society. Menopause. 2013;20(9):888-902.