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Ospemifene: Drug information

Ospemifene: Drug information
(For additional information see "Ospemifene: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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).

Brand Names: US
  • Osphena
Brand Names: Canada
  • Osphena
Pharmacologic Category
  • Selective Estrogen Receptor Modulator (SERM)
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 (Ref).

Dyspareunia, moderate to severe

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

Vaginal dryness, moderate to severe

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: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): No dosage adjustment provided in manufacturer's labeling (has not been studied). Use is not recommended.

Dosing: Older Adult

Refer to adult dosing.

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

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

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).

Dosage Forms: US

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

Tablet, Oral:

Osphena: 60 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Osphena Oral)

60 mg (per each): $9.76

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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

Tablet, Oral:

Osphena: 60 mg

Administration: Adult

Administer with food.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

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).

Medication Safety Issues
Sound-alike/look-alike issues:

Ospemifene may be confused with osimertinib, raloxifene, toremifene

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

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

Estrogen Derivatives: May enhance the adverse/toxic effect of Ospemifene. Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fluconazole: May increase the serum concentration of Ospemifene. Risk X: 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. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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

RifAMPin: May decrease the serum concentration of Ospemifene. Risk C: 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. Risk X: Avoid combination

Reproductive Considerations

Use is contraindicated in women who may become pregnant.

Pregnancy Considerations

Use is contraindicated in women who are pregnant.

Breastfeeding Considerations

It is not known if ospemifene is present in breast milk.

Breastfeeding is not recommended by the manufacturer.

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]).

Mechanism of Action

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).

Pharmacokinetics (Adult Data Unless Noted)

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

Distribution: Vd: 448 L

Protein binding: >99% bound to serum proteins

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

Bioavailability: Increased approximately two- to threefold by food

Half-life elimination: ~26 hours

Time to peak: ~2 hours (range: 1-8 hours)

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BD) Bangladesh: Osmina;
  • (DE) Germany: Senshio;
  • (ES) Spain: Senshio;
  • (GB) United Kingdom: Senshio;
  • (IT) Italy: Senshio;
  • (PR) Puerto Rico: Osphena
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.
  2. Bachmann GA and Komi JO (Ospemifene Study Group), "Ospemifene Effectively Treats Vulvovaginal Atrophy in Postmenopausal Women: Results From A Pivotal Phase 3 Study," Menopause, 2010, 17(3):480-6. [PubMed 20032798]
  3. North American Menopause Society (NAMS). The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753. doi: 10.1097/GME.0000000000000921. [PubMed 28650869]
  4. North American Menopause Society [NAMS]. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013;20(9):888-902; quiz 903-4. doi: 10.1097/GME.0b013e3182a122c2. [PubMed 23985562]
  5. Osphena (ospemifene) [prescribing information]. Princeton, NJ: Duchesnay USA Inc; May 2023.
  6. Portman DJ, Bachmann GA, Simon JA; Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623-630. doi: 10.1097/gme.0b013e318279ba64. [PubMed 23361170]
  7. Portman DJ, Gass ML; Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society. Menopause. 2014;21(10):1063-1068. doi: 10.1097/GME.0000000000000329. [PubMed 25160739]
  8. Simon JA, Altomare C, Cort S, et al. Overall safety of ospemifene in postmenopausal women from placebo-controlled phase 2 and 3 trials. J Womens Health (Larchmt). 2018;27(1):14-23. doi: 10.1089/jwh.2017.6385. [PubMed 29064335]
  9. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011. doi: 10.1210/jc.2015-2236. [PubMed 26444994]
  10. Tan O, Bradshaw K, and Carr BR, "Management of Vulvovaginal Atrophy-Related Sexual Dysfunction in Postmenopausal Women: An Up-to-Date Review," Menopause, 2012, 19(1):109-17. [PubMed 22011753]
  11. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
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