Safety profile established through 10 Phase 2/3 trials and clinical experience1Osphena® has been prescribed more than one million times in the U.S. since its launch in 20132

Safety profile established through 10 Phase 2/3 trials and clinical experience1Osphena® has been prescribed more than one million times in the U.S. since its launch in 20132

Osphena® safety and efficacy have been confirmed by multiple clinical trials:1,2

  • Largest population of postmenopausal women with vaginal dryness and dyspareunia (n=2,209)1,2
  • Ten phase 2/3 trials1
  • Long-term safety data up to 52 weeks in duration1,3
    • 847 postmenopausal women were studied for up to 52 weeks in safety studies.
  • Unlike clinical trials involving estrogen-based products, Osphena® clinical trials were performed without adding a progestin, either in women with or without an intact uterus.1,3

Osphena®’s safety information contains a Boxed Warning regarding endometrial cancer and cardiovascular disorders.

Important safety information: Common side effects and contraindications1

Common side effects may include:1

  • Hot flashes
  • Vaginal discharge
  • Muscle spasms
  • Hyperhidrosis
  • Night sweats
  • Headaches
  • Vaginal hemorrhage

Osphena® is contraindicated in patients with:1

  • 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 [MI]), or a history of these conditions
  • Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to Osphena® or any of its ingredients
  • Known or suspected pregnancy

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

Osphena® Safety Profile

Breast safety considerations2,3

Phase 2/3 clinical studies of Osphena® 60 mg, which included postmenopausal women (aged 40-80 years) with VVA.2,3

  • Patients had to have a normal clinical breast examination at screening.*
  • Patients underwent a full breast examination at screening and had follow-up assessments at 12 months and 12 weeks, 6 months, and 12 months.

These studies demonstrated the following:2,3,5

  • No clinically significant mammographic changes in Osphena®-treated patients.
  • A decrease in abnormal breast palpation findings from baseline to 52 weeks:
    • Osphena®: 2.8% at baseline (N=1102) vs. 0.8% at 52 weeks (N=354)
    • Placebo: 2.3% at baseline (N=821) vs. 0% at 52 weeks (N=90).
  • A low rate of breast-related treatment-related adverse events (2.1% Osphena® [33/1559] vs. 1.6% placebo [21/1268]).
  • No cases of breast cancer in the Osphena® group (0% vs. 0.2% [2/1268] placebo).

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.

*Obtained at screening or within 9 months prior to randomization.

†Including one case of breast cancer, in situ.

Cardiovascular (CV) data1

In clinical trials, less than 1% of patients experienced treatment-related CV events.1

Phase 2/3 clinical studies of Osphena® 60 mg, which included postmenopausal women (aged 40–80 years) with VVA, demonstrated the following:1,5,6

adverse events graph

Endometrial data

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 of study medication.1,2

There were 0 cases of endometrial cancer. There was 1 case of simple hyperplasia without atypia observed 88 days after the last dose of study medication.1,2

Osphena® has a Boxed Warning regarding endometrial cancer and cardiovascular disorders.

Osphena® is a SERM, not an estrogen1,5,7

What are SERMs?

SERMs, or selective estrogen-receptor modulators, are a well-established class of synthetic compounds that mimic estrogen effects in some tissues and inhibit estrogen effects in others.1,7

Osphena® is an estrogen receptor agonist/antagonist with tissue selective effects. Its biological actions are mediated through binding to estrogen receptors. This binding results in activation of estrogenic pathways in some tissues (agonism) and blockade of estrogenic pathways in others (antagonism).1,7

Osphena® binds to estrogen receptors but is not a hormone1,4,5

  • Acts selectively as an estrogen receptor agonist on the vagina.*,1,4,8
  • Taken orally, distributed systemically, but active locally as a function of its characteristic tissue selectivity.4,8
safety mechanism of action

*Increases superficial cells, decreases parabasal cells and reduces pH.1

 

Talk to your patients about a once daily non-hormonal oral tablet1

Osphena® is easy to prescribe and easy for patients to take.1

Osphena®
is a convenient,
once-daily medication
that fits patients’ busy
lives and does not disrupt
intimate moments.1,9
One 60 mg pill1 Once daily1 With food1 Ideally, at the same time every day1
  ic with food ic with food ic with food
hand with pill

Additional prescribing notes:1

  • Osphena® should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.
  • Do not use Osphena® in women with severe hepatic impairment.
  • Please see Full Prescribing Information for a list of contraindications, warnings and precautions.
  1. Osphena Prescribing Information. January 2019.
  2. Data on file. Duchesnay USA Inc.
  3. 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.
  4. 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.
  5. Archer DF. 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;26(6):611–621.
  6. Constantine G et al. Endometrial safety of ospemifene: results of the Phase 2/3 clinical development program. Menopause. 2015;1(22):36‐43.
  7. Pinkerton JV, Thomas S. J Steroid Biochem Mol Biol. 2014;142:142-154.
  8. Archer DF, Carr BR, Pinkerton JV, et al. Effects of ospemifene on the female reproductive and urinary tracts: translation from preclinical models into clinical evidence. Menopause. 2015;22(7):786–796.
  9. 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.

Indication and Important Safety Information including Boxed Warning

INDICATIONS:

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.

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).

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

INDICATION AND IMPORTANT SAFETY INFORMATION

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

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 AND IMPORTANT SAFETY INFORMATION

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

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).