Ospemifene

Indications

Ospemifene is used for: Dyspareunia, Vaginal Dryness

Adult Dose

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 once daily Use for the shortest duration consistent with treatment goals and risks for the individual woman Vaginal Dryness Indicated for treatment of moderate-to-severe vaginal dryness, a symptom of vulvar and vaginal atrophy, due to menopause 60 mg PO once daily Hepatic impairment Mild-to-moderate hepatic impairment: No dosage adjustment required Severe hepatic impairment: Not studied; do not use

Child Dose

Renal Dose

Renal impairment: No dosage adjustment required

Administration

Take with food; food increases bioavailability by ~2-3 fold

Contra Indications

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

Precautions

Manage risk factors for 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 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-Lactation

Pregnancy Contraindicated in women who are or may become pregnant; if a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus Based on animal data, ospemifene is likely to increase risk for adverse outcomes during pregnancy and labor Adverse findings at maternally toxic doses included embryofetal lethality in rats and rabbits, and neonatal mortality and difficult labor in rats Reproductive effects observed are consistent with, and are considered to be related to ospemifene’s estrogen receptor activity Lactation Unknown if excreted in human breast milk Do not breastfeed Animal studies Excreted in rat milk and detected at concentrations higher than that in maternal plasma

Interactions

Ospemifene should not be used concomitantly with estrogen or estrogen agonist/antagonist. Do not use fluconazole and ketoconazole concomitantly with Ospemifene as they increase serum concentrations of Ospemifene.

Side Effects

Side effects of Ospemifene : 1-10% Hot flush (7.5%) Vaginal discharge (3.8%) Muscle spasms (3.2%) Hyperhidrosis (1.6%) Genital discharge (1.3%)

Mode 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