Important Safety Information including Boxed Warning and Indication

Important Safety Information for OSPHENA®

WARNING: ENDOMETRIAL CANCER and CARDIOVASCULAR DISORDERS

Endometrial Cancer

OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. There is a potential increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adequate diagnostic measures, including directed and random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding

Cardiovascular Disorders

In clinical trials for OSPHENA (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 1.13 and 3.39 per thousand women years, respectively, in the OSPHENA 60 mg treatment group and 3.15 and 0 with placebo. The incidence of DVT was 2.26 per thousand women years (2 reported cases) in the OSPHENA 60 mg treatment group and 3.15 per thousand women years (1 reported case) with placebo. OSPHENA should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.

There is a reported increased risk of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) who received daily oral conjugated estrogens (CE) [0.625 mg]-alone therapy over 7.1 years as part of the Women’s Health Initiative (WHI).

Indication:

OSPHENA (ospemifene) is indicated for:
1.1 The treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause
1.2 The treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy, due to menopause

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 (e.g., stroke and myocardial infarction) or a history of these conditions
  • Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to OSPHENA or any of its ingredients
  • OSPHENA is contraindicated in 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/m. 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

Cardiovascular Disorders
In the clinical trials for OSPHENA (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 1.13 and 3.39 per thousand women years, respectively in OSPHENA 60 mg treatment group and 3.15 and 0 per thousand women years in placebo. Should thromboembolic or hemorrhagic stroke occur or be suspected, OSPHENA should be discontinued immediately. 

In the OSPHENA clinical trials, two cases of myocardial infarctions (MI) occurred in women receiving 60 mg of ospemifene.

In the OSPHENA clinical trials, two cases of DVT occurred in women receiving OSPHENA 60 mg. Should a VTE occur or be suspected, OSPHENA should be discontinued immediately.

If feasible, OSPHENA should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.

Malignant Neoplasms
OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has agonistic effects. In the OSPHENA clinical trials (60 mg treatment group), 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 5 mm or greater was seen in the OSPHENA up to 52 weeks treatment groups at a rate of 101.4 per thousand women vs. 20.9 per thousand women for placebo. The incidence of any type of proliferative (weakly plus active plus disordered) endometrium was 26.3 per thousand women in the OSPHENA up to 52 weeks treatment groups vs. 0 per thousand women for placebo. Uterine polyps occurred at an incidence of 19.6 per thousand women in the OSPHENA up to 52 weeks treatment groups vs. 8.3 per thousand women for placebo.

An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The greatest risk appears to be associated with prolonged use and estrogen dose. Adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer. The use of with OSPHENA therapy was not evaluated in the clinical trials.

OSPHENA 60 mg has not been adequately studied in women with breast cancer; therefore, it should not be used in women with known or suspected breast cancer.

Severe Hepatic Impairment
OSPHENA should not be used in women with severe hepatic impairment

In clinical trials the more commonly reported adverse reactions in ≥1 percent of patients treated with OSPHENA 60 mg compared to placebo were:

  1. In 12-week, double blind, placebo-controlled clinical trials were: hot flush (6.5% vs. 2.6%), vaginal discharge (3.8% vs. 0.4 %), muscle spasms (1.8% vs. 0.6%) and hyperhidrosis (1.1% vs. 0.2%)
  2. In all clinical trials up to 52-weeks (safety population) were: headaches (2.8% vs.2.4%), hot flush (12.2% vs.4.2), muscle spasms (4.5% vs. 2.4%), hyperhidrosis (2.5% vs.1.8%), night sweats (1.2% vs. 0.0%), vaginal discharge (6.00% vs. 0.6 %) and vaginal hemorrhage (1.3% vs. 0.0%).

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

  • Neoplasms Benign, Malignant and Unspecified (including 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

Drug interactions: OSPHENA is primarily metabolized by CYP3A4 and CYP2C9. CYP2C19 and other pathways contribute to the metabolism of ospemifene. Do not use estrogens or estrogen agonists/antagonists, fluconazole, ketoconazole 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.

NEW!
Osphena® now also indicated for moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy, due to menopause
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.

For U.S. Healthcare Professionals Only

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