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Ospemifene

Medically reviewed by Drugs.com. Last updated on Jun 19, 2020.

Pronunciation

(os PEM i feen)

Index Terms

  • FC1271a

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Osphena: 60 mg

Brand Names: U.S.

  • Osphena

Pharmacologic Category

  • Selective Estrogen Receptor Modulator (SERM)

Pharmacology

Ospemifene is a selective estrogen receptor modulator (SERM); it activates estrogen pathways in some tissues and blocks estrogen pathways in others, and specifically has agonistic effects on the endometrium. In women with VVA, ospemifene was shown to improve vaginal changes associated with the decrease in natural estrogen production associated with menopause (improves vaginal maturation index, decreases vaginal pH) and significantly decreased the most bothersome moderate-to-severe subjective findings reported by women (vaginal dryness and dyspareunia) after 12 weeks of therapy (Bachmann, 2010).

Distribution

Vd: 448 L

Metabolism

Hepatic via CYP3A4, 2C9, and 2C19; forms a metabolite (4-hydroxyospemifene)

Excretion

Feces (75%); urine (7%; <0.2% as unchanged drug)

Onset of Action

A significant decrease in vaginal dryness and dyspareunia were observed after 12 weeks of therapy (Bachmann, 2010).

Time to Peak

~2 hours (range: 1-8 hours)

Half-Life Elimination

~26 hours

Protein Binding

>99% bound to serum proteins

Use: Labeled Indications

Dyspareunia: Treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause

Vaginal dryness: Treatment of moderate to severe vaginal dryness, symptoms of VVA, associated with menopause

Note: The International Society for the Study of Women’s Sexual Health and The North American Menopause Society have endorsed the term genitourinary syndrome of menopause (GSM) as new terminology for vulvovaginal atrophy. The term GSM encompasses all genital and urinary signs and symptoms associated with a loss of estrogen due to menopause (Portman 2014).

Contraindications

Hypersensitivity (eg, angioedema, urticaria, rash, pruritus) to ospemifene or any component of the formulation; undiagnosed abnormal genital bleeding; DVT or PE (current or history of); active or history of arterial thromboembolic disease (eg, stroke, MI); estrogen-dependent tumor (known or suspected); women who are or may become pregnant

Dosing: Adult

General dosing guidelines: When treating symptoms of menopause, therapy should be evaluated routinely for appropriate dose, duration, and route of administration for each individual patient based on treatment goals and changes in benefits, risks, and health over time (NAMS 2017).

Dyspareunia, moderate to severe: Postmenopausal females: Oral: 60 mg once daily.

Vaginal dryness, moderate to severe: Postmenopausal females: Oral: 60 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Administer with food.

Storage

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Apalutamide: May decrease the serum concentration of Ospemifene. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ospemifene. Monitor therapy

Dicloxacillin: May decrease the serum concentration of Ospemifene. Monitor therapy

Enzalutamide: May decrease the serum concentration of Ospemifene. Monitor therapy

Estrogen Derivatives: May enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic effect of Ospemifene. Avoid combination

Fluconazole: May increase the serum concentration of Ospemifene. Avoid combination

Fluoroestradiol F18: Selective Estrogen Receptor Modulators may diminish the diagnostic effect of Fluoroestradiol F18. Management: Image patients with fluoroestradiol F-18 prior to starting systemic endocrine therapies that block the estrogen receptor. Use of fluoroestradiol F-18 should not delay indicated treatment. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of Ospemifene. Monitor therapy

RifAMPin: May decrease the serum concentration of Ospemifene. Monitor therapy

Selective Estrogen Receptor Modulators: May enhance the adverse/toxic effect of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Selective Estrogen Receptor Modulators may diminish the therapeutic effect of Ospemifene. Ospemifene may also diminish the therapeutic effects of other Selective Estrogen Receptor Modulators. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Endocrine & metabolic: Hot flash (7% to 12%)

1% to 10%:

Central nervous system: Headache (3%)

Dermatologic: Hyperhidrosis (1% to 3%), night sweats (1%)

Genitourinary: Endometrial hyperplasia (10%), vaginal discharge (4% to 6%), endometrial polyps (2%), vaginal hemorrhage (1%)

Neuromuscular & skeletal: Muscle spasm (2% to 5%)

<1%, postmarketing, and/or case reports: Angioedema, benign neoplasm, cerebrovascular accident, cyst, deep vein thrombosis, endometrial carcinoma, erythematous rash, hypersensitivity reaction, malignant neoplasm, myocardial infarction, polyp, pruritus, pulmonary embolism, skin rash, thrombosis, urticaria

ALERT: U.S. Boxed Warning

Endometrial cancer:

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

Cardiovascular disorders:

In the clinical trials for ospemifene (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 ospemifene 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 ospemifene 60 mg treatment group and 3.15 per thousand women years (1 reported case) with placebo. Ospemifene 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 (0.625 mg)–alone therapy over 7.1 years as part of the Women's Health Initiative (WHI).

Warnings/Precautions

Concerns related to adverse effects:

• Breast cancer: Ospemifene has not been adequately studied in women with breast cancer. Use is not currently recommended in women with carcinoma of the breast (known, suspected or history of) and use is contraindicated with an estrogen-dependent tumor.

• Endometrial cancer: [US Boxed Warning]: Ospemifene is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, ospemifene has estrogen agonistic effects. There is a potential increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Undertake adequate diagnostic measures, including directed and random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. For women with an intact uterus using an estrogen without a progestin, the risk of endometrial cancer is dependent upon dose and duration of therapy. Endometrial cancer was not reported in clinical studies of ospemifene (duration ≤52 weeks) and the use of progestins was not evaluated. There is no safety or efficacy data to recommend the addition of a progestin to ospemifene therapy in women with a uterus (current warnings are based on safety data for systemic hormone therapy with unopposed estrogen); evaluate appropriately if postmenopausal vaginal bleeding develops (Simon 2018).

Disease-related concerns:

• Cardiovascular disease: [US Boxed Warning]: The following were reported with ospemifene in clinical trials lasting ≤15 months duration: thromboembolic stroke 1.13/1,000 women years (placebo 3.15/1,000 women years); hemorrhagic stroke 3.39/1,000 women years (placebo 0/1,000 women years); DVT 2.26/1,000 women years (placebo 3.15/1,000 women years). Risk factors for cardiovascular disorders, arterial vascular disorders, and/or venous thromboembolism (VTE) should be managed appropriately. Risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of VTE. Discontinue immediately if a VTE, thromboembolic, or hemorrhagic stroke occur or are suspected. Use is contraindicated in women with active DVT, PE, or a history of these conditions and in women with active or recent arterial thromboembolic disease (stroke and MI) or a history of these conditions.

• Hepatic dysfunction: Has not been studied in patients with severe hepatic impairment; use is not recommended.

Special populations:

• Surgical patients: Whenever possible, discontinue at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.

Other warnings/precautions:

• Risks vs benefits: [US Boxed Warning]: Ospemifene should be used for the shortest duration possible consistent with treatment goals and risks for the individual woman. With appropriate clinical monitoring, use may continue as long as bothersome symptoms are present (NAMS 2013).

Monitoring Parameters

Evaluate baseline risk for breast cancer and CVD prior to therapy. Efficacy and side effects beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate; age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer). Duration of treatment should be evaluated at least annually (ES [Stuenkel 2015]).

Reproductive Considerations

Use is contraindicated in women who may become pregnant.

Pregnancy Considerations

Use is contraindicated in women who are pregnant.

Patient Education

What is this drug used for?

• It is used to treat vaginal pain during sex caused by changes that happen with menopause.

• It is used to treat vaginal irritation and dryness caused by menopause.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hot flashes

• Vaginal pain, itching, and discharge

• Muscle spasms

• Night sweats

• Sweating a lot

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight

• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood

• Severe loss of strength and energy

• Severe headache

• Lump in breast

• Breast soreness

• Vaginal bleeding

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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