Overview
11 DESCRIPTION FARESTON (toremifene citrate) Tablets for oral administration each contain 88.5 mg of toremifene citrate, which is equivalent to 60 mg toremifene. FARESTON is an estrogen agonist/antagonist. The chemical name of toremifene is: 2-{p-[(Z)-4-chloro-1,2-diphenyl-1-butenyl]phenoxy}-N,N-dimethylethylamine citrate (1:1).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. In general, however, nonsteroidal triphenylethylene derivatives are predominantly antiestrogenic in rats and humans and estrogenic in mice. In rats, toremifene causes regression of established dimethylbenzanthracene (DMBA)-induced mammary tumors. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, i.e.
Indications
- 1 INDICATIONS AND USAGE FARESTON® is an estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. FARESTON® is an estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. ( 1 )
Common Doses
- 60 mg
Dosage
2 DOSAGE AND ADMINISTRATION The dosage of FARESTON is 60 mg, once daily, orally. Treatment is generally continued until disease progression is observed. 60 mg once daily, orally ( 2 )
Black Box Warning
WARNING: QT PROLONGATION FARESTON has been shown to prolong the QTc interval in a dose- and concentration-related manner [see Clinical Pharmacology (12.2) ] . Prolongation of the QT interval can result in a type of ventricular tachycardia called Torsade de pointes, which may result in syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital/acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided [see Warnings and Precautions (5.1) ] .
Contraindications
- 4 CONTRAINDICATIONS Hypersensitivity to the drug ( 4.1 ) QT Prolongation, Hypokalemia, Hypomagnesemia ( 4.2 ) 4.1 Hypersensitivity to the Drug FARESTON is contraindicated in patients with known hypersensitivity to the drug. 4.2 QT Prolongation, Hypokalemia, Hypomagnesemia Toremifene should not be prescribed to patients with congenital/acquired QT prolongation (long QT syndrome), uncorrected hypokalemia, or uncorrected hypomagnesemia.
Side Effects
- 6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Most common adverse reactions are hot flashes, sweating, nausea and vaginal discharge. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kyowa Kirin, Inc. at 1-800-305-FARESTON (1-800-305-3273) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS Drugs that decrease renal calcium excretion, e.g., thiazide diuretics, may increase the risk of hypercalcemia in patients receiving FARESTON. ( 7.1 ) Agents that prolong QT should be avoided. ( 7.2 ) Coadministration with a strong CYP3A4 inducer may result in a relevant decrease in FARESTON exposure and should be avoided. ( 7.3 ) Coadministration with a strong CYP3A4 inhibitor can result in a relevant increase in FARESTON exposure and should be avoided. ( 7.