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Toremifene Citrate

Pronunciation: tore-EM-i-feen
Class: Antiestrogen

Trade Names

- Tablets, oral 60 mg


An estrogen agonist/antagonist that blocks the growth-stimulating effects of estrogen in the tumor.



Well absorbed; absorption is not influenced by food. T max is 3 h. Steady state is reached in approximately 4 to 6 wk.


Vd is 580 L. Approximately 99.5% is bound to plasma proteins, mainly albumin. Mean distribution half-life is approximately 4 h.


Extensively metabolized, principally by CYP3A4 to N-demethyltoremifene.


Mean total Cl is approximately 5 L/h. Elimination is primarily in feces (as metabolites), with approximately 10% excreted in urine during a 1-wk period. Elimination is slow. Half-life is approximately 5 days.

Special Populations

Renal Function Impairment

Pharmacokinetics are similar in patients with impaired kidney function and in healthy patients.

Hepatic Function Impairment

The mean elimination half-life was increased by less than 2-fold in patients with cirrhosis or fibrosis.


Increases in elimination half-life (4 vs 7 days) and Vd (457 vs 627 L) were observed in elderly women.


Pharmacokinetics have not been studied in different races.

Indications and Usage

Metastatic breast cancer in postmenopausal women.


Congenital/acquired QT prolongation; hypersensitivity to any component of the product; uncorrected hypokalemia or hypomagnesemia.

Dosage and Administration

Breast Cancer

PO 60 mg once daily with or without food. Treatment is generally continued until disease progression is observed.


Store between 59° and 86°F. Protect from heat and light.

Drug Interactions

CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin)

Toremifene is a weak CYP2C9 inhibitor. Plasma concentrations of these agents may be increased. Coadminister CYP2C9 substrates with a narrow therapeutic index (eg, phenytoin, warfarin) with caution. Carefully monitor substrate concentrations (if available), appropriate laboratory markers, and signs and symptoms of increased drug exposure.

Drugs that decrease renal calcium excretion (eg, thiazide diuretics [eg, hydrochlorothiazide])

The risk of hypercalcemia may be increased. Monitor serum calcium. If hypercalcemia occurs, institute appropriate measures. If hypercalcemia is severe, discontinue one or both agents.

Drugs that prolong the QT interval (eg, amitriptyline, class 1A antiarrhythmic agents [eg, disopyramide, procainamide, quinidine], class III antiarrhythmic agents [eg, amiodarone, dofetilide, ibutilide, sotalol], clarithromycin, erythromycin, granisetron, haloperidol, levofloxacin, ofloxacin, ondansetron, thioridazine, venlafaxine)

The risk of life-threatening arrhythmias, including torsades de pointes, may be increased. If coadministration cannot be avoided, or if toremifene therapy cannot be interrupted, closely monitor patients for QT interval prolongation.

Grapefruit juice

Toremifene plasma concentrations may be elevated, increasing the risk of adverse reactions. Patients taking toremifene should avoid grapefruit juice.

Strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)

Steady-state toremifene concentration may be reduced, decreasing the pharmacologic effects. Monitor the clinical response and adjust the toremifene dose as needed.

Strong CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)

Steady-state toremifene concentration may be elevated, increasing the pharmacologic effects and risk of adverse reactions. If coadministration cannot be avoided or if toremifene therapy cannot be interrupted, closely monitor patients for QT interval prolongation.

Adverse Reactions


Arrhythmia, cerebrovascular accident/transient ischemic attack, pulmonary embolism, thrombophlebitis, thrombosis (2%); cardiac failure, MI (1%).


Dizziness (9%).


Cataracts (10%); dry eyes (9%); abnormal visual fields (4%); abnormal vision/diplopia, corneal keratopathy, glaucoma (2%).


Hot flashes (35%); sweating (20%).


Nausea (14%); vomiting (4%).


Vaginal discharge (13%); vaginal bleeding (2%).


Leukopenia; thrombocytopenia.


Elevated alkaline phosphatase, elevated AST (19%); elevated bilirubin (2%).


Edema (5%); hypercalcemia (3%).



QT prolongation

Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Prolongation of the QT interval can result in torsades 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.


Obtain periodic CBCs, calcium levels, and LFTs. Closely monitor patients with bone metastases for hypercalcemia during the first weeks of treatment. Monitor leukocyte and platelet counts in patients with leukopenia and thrombocytopenia. Obtain ECGs at baseline and as clinically indicated. Periodically monitor magnesium and potassium during therapy.


Category D .




No indication for use in children.

Hypercalcemia and tumor flare

Hypercalcemia and tumor flare have been reported in some patients with bone metastases during the first weeks of treatment. Discontinue treatment if severe hypercalcemia occurs.

Thromboembolic disease

Avoid in patients with a history of thromboembolic diseases.


Endometrial hyperplasia and cancer have been reported. Avoid long-term use in patients with preexisting endometrial hyperplasia.



Ataxia, dizziness, headache, nausea, reversible hallucinations, vertigo, vomiting.

Patient Information

  • Instruct patient to contact their health care provider if vaginal bleeding occurs.
  • Inform patients that toremifene may cause fetal harm and increase the risk of pregnancy loss. Advise premenopausal women taking toremifene to use nonhormonal contraception during treatment.
  • Inform patients with bone metastases of typical signs/symptoms of hypercalcemia and to contact their health care provider if such signs or symptoms occur.
  • Advise patients who take potent CYP3A4 inhibitors or medications that prolong the QT interval of the effects of toremifene on QT interval.
  • Advise patients to avoid taking foods that inhibit CYP3A4, including grapefruit products, because they may increase toremifene concentrations.
  • Advise patients that certain medicines, including OTC medications or herbal supplements (such as St. John's wort) and toremifene, can reduce concentrations of coadministered drugs.

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