(tore EM i feen)
- Toremifene Citrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Fareston: 60 mg
Brand Names: U.S.
- Antineoplastic Agent, Estrogen Receptor Antagonist
- Selective Estrogen Receptor Modulator (SERM)
Nonsteroidal, triphenylethylene derivative with potent antiestrogenic properties (also has estrogenic effects). Competitively binds to estrogen receptors on tumors and inhibits the growth stimulating effects of estrogen.
Vd: 580 L
Extensively hepatic, principally by CYP3A4 to N-demethyltoremifene (a weak antiestrogen)
Primarily feces; urine (~10%) during a 1-week period
Time to Peak
Serum: ≤3 hours
Toremifene: ~5 days, ~7 days (females > 60 years); N-demethyltoremifene: 6 days
Plasma: >99.5%, primarily to albumin
Special Populations: Hepatic Function Impairment
The mean elimination half-life was increased by less than 2-fold in patients with cirrhosis or fibrosis.
Special Populations: Elderly
Elimination half-life prolonged and Vd increased (457 vs 627 L) observed in elderly women.
Use: Labeled Indications
Breast cancer, metastatic: Treatment of metastatic breast cancer in postmenopausal women with estrogen receptor positive or estrogen receptor status unknown tumors
Treatment of soft tissue sarcoma (desmoid tumors)
Known hypersensitivity to toremifene or any component of the formulation; long QT syndrome (congenital or acquired QT prolongation), uncorrected hypokalemia, uncorrected hypomagnesemia
Breast cancer, metastatic: Postmenopausal women: Oral: 60 mg once daily, continue until disease progression.
Soft tissue sarcoma (desmoid tumors) (off-label use): Oral: 180 mg once daily until disease progression or unacceptable toxicity (Fiore, 2011) or 200 mg daily; in some patients with tumor progression, the dose was increased to 400 to 600 mg daily (Brooks, 1992). Additional data may be necessary to further define the role of toremifene in this condition.
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments listed in the manufacturer’s labeling. However, pharmacokinetics in patients with renal impairment are similar to those in patients with normal renal function and dosage adjustment is unlikely to be necessary.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling. However, hepatic impairment increases the half-life of toremifene.
Administer with or without food.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Avoid grapefruit juice.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from heat. Protect from light.
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Toremifene. Avoid combination
CYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Avoid combination
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Grapefruit Juice: May increase the serum concentration of Toremifene. Avoid combination
Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination
Indapamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Consider therapy modification
Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
MiFEPRIStone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Ospemifene: Selective Estrogen Receptor Modulators may enhance the adverse/toxic effect of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Selective Estrogen Receptor Modulators may diminish the therapeutic effect of Ospemifene. Ospemifene may also diminish the therapeutic effects of other Selective Estrogen Receptor Modulators. Avoid combination
QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Sugammadex: Toremifene may diminish the therapeutic effect of Sugammadex. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypercalcemic effect of Toremifene. Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Vinflunine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Vitamin K Antagonists (eg, warfarin): Toremifene may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Endocrine & metabolic: Hot flashes (35%)
Gastrointestinal: Nausea (14%)
Genitourinary: Vaginal discharge (13%)
Hepatic: Alkaline phosphatase increased (8% to 19%), AST increased (5% to 19%)
Miscellaneous: Diaphoresis (20%)
1% to 10%:
Cardiovascular: Edema (5%), arrhythmia (≤2%), CVA/TIA (≤2%), thrombosis (≤2%), cardiac failure (≤1%), MI (≤1%)
Central nervous system: Dizziness (9%)
Endocrine & metabolic: Hypercalcemia (≤3%)
Gastrointestinal: Vomiting (4%)
Genitourinary: Vaginal bleeding (2%)
Hepatic: Bilirubin increased (1% to 2%)
Local: Thrombophlebitis (≤2%)
Ocular: Cataracts (≤10%), xerophthalmia (≤9%), visual field abnormal (≤4%), corneal keratopathy (≤2%), glaucoma (≤2%), vision abnormal/diplopia (≤2%)
Respiratory: Pulmonary embolism (≤2%)
<1% (Limited to important or life-threatening): Alopecia, angina, ataxia, blurred vision, corneal opacity (reversible), corneal verticulata, depression, dermatitis, dyspnea, endometrial cancer, endometrial hyperplasia, hepatitis (toxic), incoordination, ischemic attack, jaundice, lethargy, leukopenia, paresis, pruritus, QT prolongation, rigors, skin discoloration, thrombocytopenia, tremor, tumor flare, vertigo, weakness
Concerns related to adverse effects:
• Bone marrow suppression: Leukopenia and thrombocytopenia have been reported rarely; monitor leukocyte and platelet counts in patients with leukopenia and thrombocytopenia.
• Gynecologic effects: Endometrial hyperplasia has been reported; some patients have developed endometrial cancer, although the role of toremifene in endometrial cancer development has not been established. Avoid long-term use in patients with pre-existing endometrial hyperplasia.
• Hypercalcemia: May occur during the first weeks of treatment in breast cancer patients with bone metastases; monitor closely for hypocalcemia. Institute appropriate measures if hypercalcemia occurs; discontinue treatment if severe. Medications that decrease renal calcium excretion (eg, thiazide diuretics) may increase the risk of hypercalcemia in patients receiving toremifene.
• QT prolongation: [US Boxed Warning]: May prolong the QT interval; QTc prolongation is dose-dependent and concentration dependent. QT prolongation may lead to a form of ventricular tachycardia called torsades de pointes, which may result in syncope, seizure and/or sudden death. Use is contraindicated in patients with congenital or acquired QT prolongation (long QT syndrome), uncorrected hypokalemia, or uncorrected hypomagnesemia. Avoid use with other medications known to prolong the QT interval and with strong CYP3A4 inhibitors. If concurrent use with QT prolonging agents cannot be avoided, interrupt treatment with toremifene. Use with caution in patients with heart failure, hepatic impairment, or electrolyte abnormalities. Monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Obtain ECG at baseline and as clinically indicated in patients at risk for QT prolongation.
• Tumor flare: May occur during the first weeks of treatment in breast cancer patients with bone metastases. Tumor flare consists of diffuse musculoskeletal pain and erythema with initial increased size of tumor lesions (which later regress). It is often accompanied by hypercalcemia and does not imply treatment failure or represent tumor progression.
• Hepatic impairment: The half-life of toremifene is increased (less than 2-fold) in patients with hepatic impairment (cirrhosis and fibrosis), although the pharmacokinetics of N-demethyltoremifene (a metabolite with weak antitumor potency) were unchanged.
• Thromboembolic disease: Avoid use in patients with a history of thromboembolic disease.
Concurrent drug therapy issues:
• Drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
CBC with differential (periodically), electrolytes (magnesium and potassium prior to and periodically during treatment; calcium periodically), hepatic function (periodically). Obtain ECG (baseline and periodically during treatment) in patients at risk for QT prolongation. In patients with bone metastases, monitor closely for hypercalcemia during the first few weeks of treatment.
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. Based on the mechanism of action, may cause fetal harm if administered during pregnancy. Toremifene is only approved for use in postmenopausal women; however, if prescribed in premenopausal women, effective non-hormonal contraception should be used.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience hot flashes, lack of appetite, sweating a lot, or vaginal discharge. Have patient report immediately to prescriber signs of high calcium (weakness, confusion, feeling tired, headache, nausea and vomiting, constipation, or bone pain), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, tachycardia, arrhythmia, severe dizziness, passing out, coughing up blood, severe nausea, vomiting, vision changes, depression, chills, pharyngitis, hallucinations, muscle pain, seizures, shortness of breath, tremors, bruising, bleeding, or vaginal bleeding (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about toremifene
- Other brands: Fareston