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.
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).
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.
No dosage adjustment necessary.
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.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Osphena: 60 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Osphena: 60 mg
Administer with food.
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).
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).
Ospemifene may be confused with osimertinib, raloxifene, toremifene
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
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
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).
Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Estrogen Derivatives: May enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic 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. Selective Estrogen Receptor Modulators may diminish the therapeutic effect of Ospemifene. Ospemifene may also diminish the therapeutic effects of other Selective Estrogen Receptor Modulators. Risk X: Avoid combination
Use is contraindicated in women who may become pregnant.
Use is contraindicated in women who are pregnant.
It is not known if ospemifene is present in breast milk.
Breastfeeding is not recommended by the manufacturer.
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]).
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).
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)
Tablets (Osphena Oral)
60 mg (per each): $9.76
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