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:

  • The treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
  • 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 (e.g., 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/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

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 progestins 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: 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): 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 increased exposure of that drug or ospemifene.

Please see Full Prescribing Information for OSPHENA (ospemifene) tablets, including Boxed Warning regarding Endometrial Cancer and Cardiovascular Disorders, and Patient Information at osphena.com/hcp.

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

NEW! Osphena®

Now also indicated for moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy due to menopause

Osphena® is the first and only selective estrogen receptor modulator (SERM) approved to treat moderate to severe vaginal dryness, the most common bothersome symptom of vulvar and vaginal atrophy (VVA) due to menopause.1-4

Once-daily Osphena® tablets are:

  • Non-hormonal
  • Administered orally, distributed systemically, active locally as a function of their characteristic tissue selectivity.5,6
  • Differentiated by their agonistic activity in vaginal tissue.5,6

Osphena® is an estrogen agonist/antagonist indicated for:

  • The treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy due to menopause
  • The treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy due to menopause

Vaginal dryness is the most common bothersome symptom among menopausal women1,2

 

With Osphena®, there is no need for vaginal administration

Prescribe Osphena® to offer your patients the convenience of a once-daily oral tablet that can be taken any time (with food, ideally at the same time of day).

Order samples now

Over 1 million Osphena® prescriptions have been written since its launch in 2013.8

 

Osphena®'s safety and efficacy have been confirmed in multiple clinical trials1

OVERALL SAFETY1,8

Largest studied population of postmenopausal women with dyspareunia and vaginal dryness

The safety of Osphena® has been assessed in 10 Phase 2/3 trials (n=2,209), with daily dosage ranging from 5 to 90 mg

Long-term safety data up to 52 weeks (n=847) with no cases of endometrial cancer1

EFFICACY IN MODERATE TO SEVERE VAGINAL DRYNESS TRIALS1,6

Secondary endpoints: significant improvement seen as early as 4 weeks (the most bothersome symptom, vaginal dryness; pH; superficial cells; and parabasal cells)6

Significant improvement in all co-primary endpoints at 12 weeks in two studies (the most bothersome symptom, vaginal dryness; pH; superficial cells; and parabasal cells)1,6

No unanticipated treatment-related adverse events were reported over 12 weeks.6

RESULTS AFTER 12 WEEKS OF TREATMENT1,6

After just 12 weeks of treatment, studies showed a statistically significant increase in the proportion of superficial cells and a decrease in the proportion of parabasal cells on a vaginal smear.

 

1 Osphena Prescribing Information. January 2019.
2 Kingsberg SA, Wysocki S, Magnus L, et al. 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;10:1790–1799.
3 Kingsberg SA, 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;14:413-424.
4 Simon JA, Altomare C, Cort S, et al. Overall safety of ospemifene in postmenopausal women from placebo-controlled phase 2 and 3 trials. J Women’s Health. 2018;27(1):14–23.
5 Simon JA, Davis SR, Althof SE, et al. Sexual well-being after menopause: An International Menopause Society White Paper, Climacteric. 2018; 21(5):415-427.
6 Archer DF, Goldstein SR, Simon JA, et al. Efficacy and safety of ospemifene in postmenopausal women with moderate-to-severe vaginal dryness: a phase 3, randomized, double-blind, placebo-controlled, multicenter trial. Menopause. 2019 Jan 28.
7 North American Menopause Society. Management of symptomatic vulvovaginal atrophy: 2013position statement of The North American Menopause Society. Menopause. 2013;20(19):888–902
8 Data on file.

For U.S. Healthcare Professionals Only