Dosing and uses of Osphena (ospemifene)
Adult dosage forms and strengths
tablet
- 60mg
Dyspareunia
Estrogen agonist/antagonist indicated for treatment of moderate-to-severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause
60 mg PO qDay with food
Dosage modifications
Renal impairment: No dosage adjustment required
Mild-to-moderate hepatic impairment: No dosage adjustment required
Severe hepatic impairment: Not studied; do not use
Pediatric dosage forms and strengths
Safety and efficacy not established
Osphena (ospemifene) adverse (side) effects
1-10%
Hot flush (7.5%)
Vaginal discharge (3.8%)
Muscle spasms (3.2%)
Hyperhidrosis (1.6%)
Genital discharge (1.3%)
Postmarketing reports
Hypersensitivity
Angioedema
Rash
Rash, erythematous
Generalized rash
Pruritus
Urticaria
Warnings
Black box warnings
Endometrial cancer
- Elicits estrogenic agonistic effects in the endometrium Increased risk of endometrial cancer in women with a uterus who uses unopposed estrogens (ie, without a progestin to reduce endometrial hyperplasia)
- 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 effects
- Increased risk of stroke and DVT reported in postmenopausal women who received daily oral conjugated estrogens [0.625 mg]-alone therapy over 7.1 years as part of the Women’s Health Initiative study
- In ospemifene clinical trials, the incidence of DVT was 1.45 per thousand women with ospemifene 60 mg compared with 1.04 per thousand women taking placebo
Contraindications
Undiagnosed abnormal genital bleeding
Known or suspected estrogen-dependent neoplasia
History of, or active DVT or PE History of, or active arterial thromboembolic disease (eg, stroke, MI)
Known or suspected pregnancy or women who may become pregnant
Documented hypersensitivity to drug or ingredients
Cautions
Manage cardiovascular disorders, arterial vascular disease (eg, hypertension, DM, smoking, hypercholesterolemia, obesity), and/or venous thromboembolism to reduce risk for progression to serious disease
Increased risk for endometrial hyperplasia (see Black box warnings)
Has not been studied in women with breast cancer; do not use with known or suspected breast cancer or history of breast cancer
Do not use with severe hepatic impairment (not studied)
Ospemifene is primarily metabolized by CYP3A4 and CYP2C9; CYP2C19 also contributes to its metabolism; avoid moderate-to-strong inhibitors of these isoenzymes as they may increase risk of adverse effects
May initiate or increase occurrence of hot flashes in some women
Pregnancy and lactation
Pregnancy category: X
Lactation: Unknown whether distributed in human breast milk; do not breastfeed
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Osphena (ospemifene)
Mechanism of action
Estrogen agonist/antagonist with tissue selective effects; its biological actions are mediated through binding to estrogen receptors resulting in activation of estrogenic pathways in some tissues and blockade in others
Absorption
Peak plasma time: 2 hr (fasted); 2.5 hr (high fat/high calorie meal)
Peak plasma concentration: 533 ng/mL (fasted); 1198 ng/mL (high fat/high calorie meal)
AUC: 4165 ng•h/mL (fasted); 7521 ng•h/mL (high fat/high calorie meal)
Distribution
Protein bound: >99%
Vd: 448 L
Metabolism
Metabolized by CYP3A4, CYP2C9, and CYP2C19
Elimination
Half-life: 26 hr
Total body clearance: 9.16 L/hr
Excretion: 75% feces, 7% urine
