(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 unknown tumors
Off Label Uses
Desmoid tumors (aggressive fibromatosis)
Data from a retrospective review supports the use of toremifene for the treatment of desmoid tumors [Fiore 2015]. Data from a limited number of patients studied (case reports) also suggests that toremifene may be beneficial for the treatment of desmoid tumors [Brooks 1992]. Additional data may be necessary to further define the role of toremifene in this condition.
Known hypersensitivity to toremifene or any component of the formulation; congenital/acquired QT prolongation (long QT syndrome), uncorrected hypokalemia, uncorrected hypomagnesemia
Breast cancer, metastatic: Postmenopausal women: Oral: 60 mg once daily, continue until disease progression.
Desmoid tumors (aggressive fibromatosis) (off-label use): Oral: 180 mg once daily until disease progression or unacceptable toxicity (Fiore 2015). 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.
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.
Bilastine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Buprenorphine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. 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
Hydroxychloroquine: May enhance the QTc-prolonging effect of 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
Probucol: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Promazine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. 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
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
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
Teneligliptin: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. 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
Xipamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy
Dermatologic: Diaphoresis (20%)
Endocrine & metabolic: Hot flash (35%)
Gastrointestinal: Nausea (14%)
Genitourinary: Vaginal discharge (13%)
Hepatic: Increased serum alkaline phosphatase (8% to 19%), increased serum AST (5% to 19%)
1% to 10%:
Cardiovascular: Edema (5%), cardiac arrhythmia (≤2%), cerebrovascular accident (≤2%), local thrombophlebitis (≤2%), pulmonary embolism (≤2%), thrombosis (≤2%), transient ischemic attacks (≤2%), cardiac failure (≤1%), myocardial infarction (≤1%)
Central nervous system: Dizziness (9%)
Endocrine & metabolic: Hypercalcemia (≤3%)
Gastrointestinal: Vomiting (4%)
Genitourinary: Vaginal hemorrhage (2%)
Hepatic: Increased serum bilirubin (1% to 2%)
Ophthalmic: Cataract (≤10%), xerophthalmia (≤9%), visual field defect (≤4%), corneal disease (≤2%), glaucoma (≤2%), visual disturbance (≤2%), diplopia (≤2%)
<1% (Limited to important or life-threatening): Alopecia, angina pectoris, ataxia, blurred vision, corneal opacity (reversible; including corneal verticulata), depression, dermatitis, dyspnea, endometrial carcinoma, endometrial hyperplasia, jaundice, lethargy, leukopenia, paresis, prolonged Q-T interval on ECG, pruritus, rigors, skin discoloration, thrombocytopenia, toxic hepatitis, 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.
• Hepatotoxicity: Grades 3 and 4 transaminase increases and hyperbilirubinemia have been reported, including jaundice, hepatitis, and non-alcoholic fatty liver disease. Monitor liver function tests periodically.
• Hypercalcemia: May occur during the first weeks of treatment in breast cancer patients with bone metastases; monitor closely for hypercalcemia. 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.
• Uterine malignancy: Endometrial cancer, hypertrophy, hyperplasia, and uterine polyps have been reported. Long-term use of toremifene in patients with pre-existing endometrial hyperplasia has not been established. Baseline and annual gynecological exams are recommended in all patients; closely monitor patients who are at high risk for endometrial cancer.
• 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.
CBC with differential (periodically), electrolytes (magnesium and potassium prior to and periodically during treatment; calcium periodically), hepatic function tests (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. Baseline and annual gynecological exams (patients at high risk for endometrial cancer should be closely monitored). Signs/symptoms of uterine disorders (bleeding, discharge, pelvic pain/pressure).
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
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
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- Drug class: hormones/antineoplastics
Other brands: Fareston