toremifene (Rx)

>10%

Hot flashes (35%)

Sweating (20%)

Nausea (14%)

Vaginal discharge (13%)

1-10%

Cataracts (10%)

Dizziness (9%)

Edema (5%)

Vomiting (4%)

Dry eyes (4%)

Hypercalcemia (3%)

Thrombophlebitis (2%)

Vaginal bleeding (2%)

<1%

Alopecia

Angina

Hepatitis

Dermatitis

Depression

Corneal opacity

Postmarketing

Hepatototoxicity

Risk of uterine malignancy

Contraindications

Hypersensitivity

Estrogen receptor-negative tumors

Thromboembolic history

Should not be prescribed to patients with congenital/acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia

Cautions

May increase risk of ovarian CA, osteosarcoma

Risk of hypercalcemia & tumor flare

Long-term treatment discouraged in preexisting endometrial hyperplasia

Prolongs QTc interval; avoid in patients with congenital/acquired QT prolongation or uncorrected hypokalemia/hypomagnesemia

Avoid concomitant use of drugs known to prolong QT interval

Hepatotoxicity, both increases in serum concentration for grade 3 and 4 transaminitis; hyperbilirubinemia, including jaundice, hepatitis, and non-alcoholic fatty liver disease, have also been reported in clinical trials and postmarketing; liver function tests should be performed periodically

Endometrial cancer, endometrial hypertrophy, hyperplasia, and uterine polyps reported; endometrial hyperplasia of uterus observed in animals treated with toremifene; long-term use has not been established in patients with pre-existing endometrial hyperplasia; all patients should have baseline and annual gynecological examinations; patients at high risk of endometrial cancer should be closely monitored

Pregnancy Category: D

Lactation: Not known if excreted in breast milk, indicated in postmenopausal women

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.

Mechanism of Action

Selective estrogen receptor modulator: nonsteroidal estrogen, agonist/antagonist, competes for estrogen binding sites on breast tumor cells

Pharmacokinetics

Half-Life: 5 days

Peak Plasma Time: 3 hr

Protein Bound: >99.5%

Vd: 580 L

Metabolism: Hepatic CYP3A4

Metabolites: N-demethyltoremifene, (deamino-hydroxy) toremifene

Clearance: 5 L/hr

Excretion: Feces (primarily); urine (10%)