Fareston (Toremifene)
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Fareston (Toremifene)

FARESTON®
(toremifene citrate)

WARNING: QT PROLONGATION

FARESTON has been shown to prolong the QTc interval in a dose- and concentration-related manner [see CLINICAL PHARMACOLOGY]. 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].

DRUG 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-1,2diphenyl-1-butenyl]phenoxy}-N,N-dimethylethylamine citrate (1:1). The structural formula is:

FARESTON® (toremifene citrate) Structural Formula Illustration

and the molecular formula is C26H28ClNO • C6H8O7. The molecular weight of toremifene citrate is 598.10. The pKa is 8.0. Water solubility at 37°C is 0.63 mg/mL and in 0.02N HCl at 37°C is 0.38 mg/mL.

FARESTON is available only as tablets for oral administration. Inactive ingredients: colloidal silicon dioxide, lactose, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, and starch.

What are the possible side effects of toremifene (Fareston)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using toremifene and call your doctor at once if you have a serious side effect such as:

  • severe dizziness, fainting, fast or pounding heartbeats, seizure (convulsions);
  • nausea, vomiting, stomach pain, loss of appetite, constipation, increased thirst or urination, muscle pain or weakness, joint pain, confusion, and feeling tired or restless;
  • easy bruising, unusual bleeding, purple or red...

Read All Potential Side Effects and See Pictures of Fareston »

What are the precautions when taking toremifene (Fareston)?

See also Warning section.

Before taking toremifene, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bone cancer (metastases), blood disorders (e.g., anemia, low platelets), diabetes, history of stroke or other blood clots (e.g., in the legs, lungs), heart disease (e.g., heart attack, irregular heartbeat), high blood pressure, liver disease, long periods of sitting or lying down (e.g., immobility such as being bedridden), uterus problems such as endometrial hyperplasia.

This drug may...

Read All Potential Precautions of Fareston »

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

FARESTON® is an estrogen agonist/antagonist indicated for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors.

DOSAGE AND ADMINISTRATION

The dosage of FARESTON is 60 mg, once daily, orally. Treatment is generally continued until disease progression is observed.

HOW SUPPLIED

Dosage Forms And Strengths

Tablet is 60 mg, round, convex, unscored, uncoated, and white, or almost white, identified with TO 60 embossed on one side.

Storage And Handling

FARESTON Tablets, containing toremifene citrate in an amount equivalent to 60 mg of toremifene, are round, convex, unscored, uncoated, and white, or almost white.

FARESTON Tablets are identified with TO 60 embossed on one side.

FARESTON Tablets are available as:

NDC 11399-005-30 bottles of 30
NDC
11399-005-01 bottles of 100
NDC
11399-005-07 samples of 7

Store at 25°C (77°F).

Excursions permitted to 15-30°C (59-86°F)

[See USP Controlled Room Temperature.]

Protect from heat and light.

Distributed by GTx, Inc. Memphis, TN 38103, USA. Rev. 03/2011

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

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.

Clinical Trials Experience

Adverse drug reactions are principally due to the antiestrogenic actions of FARESTON and typically occur at the beginning of treatment.

The incidences of the following eight clinical toxicities were prospectively assessed in the North American Study. The incidence reflects the toxicities that were considered by the investigator to be drug related or possibly drug related.

  North American Study
FAR60
n = 221
TAM20
n = 215
Hot Flashes 35% 30%
Sweating 20% 17%
Nausea 14% 15%
Vaginal Discharge 13% 16%
Dizziness 9% 7%
Edema 5% 5%
Vomiting 4% 2%
Vaginal Bleeding 2% 4%

Approximately 1% of patients receiving FARESTON (n = 592) in the three controlled studies discontinued treatment as a result of adverse reactions (nausea and vomiting, fatigue, thrombophlebitis, depression, lethargy, anorexia, ischemic attack, arthritis, pulmonary embolism, and myocardial infarction).

Serious adverse reactions occurring in at least 1% of patients receiving FARESTON in the three major trials are listed in the table below.

Three prospective, randomized, controlled clinical studies (North American, Eastern European, and Nordic) were conducted. The patients were randomized to parallel groups receiving FARESTON 60 mg (FAR60) or tamoxifen 20 mg (TAM20) in the North American Study or tamoxifen 40 mg (TAM40) in the Eastern European and Nordic studies. The North American and Eastern European studies also included high-dose toremifene arms of 200 and 240 mg daily, respectively [see Clinical Studies].

Adverse Reactions North American Eastern European Nordic
FAR 60
n=221 (%)
TAM 20
n=215 (%)
FAR 60
n=157 (%)
TAM 40
n=149 (%)
FAR 60
n=214 (%)
TAM 40
n=201 (%)
Cardiac
Cardiac Failure 2 (1) 1 ( < 1) -   1 ( < 1) 2 (1) 3 (1.5)
Myocardial Infarction 2 (1) 3 (1.5) 1 ( < 1) 2 (1) -   1 ( < 1)
Arrhythmia -   -   -   -   3 (1.5) 1 ( < 1)
Angina Pectoris -   -   1 ( < 1) -   1 ( < 1) 2 (1)
Ocular*
Cataracts 22 (10) 16 (7.5) -   -   -   5 (3)
Dry Eyes 20 (9) 16 (7.5) -   -   -   -  
Abnormal Visual Fields 8 (4) 10 (5) -   -   -   1 ( < 1)
Corneal Keratopathy 4 (2) 2 (1) -   -   -   -  
Glaucoma 3 (1.5) 2 (1) 1 ( < 1) -   -   1 ( < 1)
Abnormal Vision/Diplopia -   -   -   -   3 (1.5) -  
Thromboembolic
Pulmonary Embolism 4 (2) 2 (1) 1 ( < 1) -   -   1 ( < 1)
Thrombophlebitis -   2 (1) 1 ( < 1) 1 ( < 1) 4 (2) 3 (1.5)
Thrombosis -   1 ( < 1) 1 ( < 1) -   3 (1.5) 4 (2)
CVA/TIA 1 ( < 1) -   -   1 ( < 1) 4 (2) 4 (2)
Elevated Liver Tests**
AST 11 (5) 4 (2) 30 (19) 22 (15) 32 (15) 35 (17)
Alkaline Phosphatase 41 (19) 24 (11) 16 (10) 13 (9) 18 (8) 31 (15)
Bilirubin 3 (1.5) 4 (2) 2 (1) 1 ( < 1) 2 (1) 3 (1.5)
Hypercalcemia 6 (3) 6 (3) 1 ( < 1) -   -   -  
* Most of the ocular abnormalities were observed in the North American Study in which on-study and biannual ophthalmic examinations were performed. No cases of retinopathy were observed in any arm.
** Elevated defined as follows: North American Study: AST > 100 IU/L; alkaline phosphatase > 200 IU/L; bilirubin > 2 mg/dL. Eastern European and Nordic studies: AST, alkaline phosphatase, and bilirubin – WHO Grade 1 (1.25 times the upper limit of normal).

Other adverse reactions included leukopenia and thrombocytopenia, skin discoloration or dermatitis, constipation, dyspnea, paresis, tremor, vertigo, pruritus, anorexia, reversible corneal opacity (corneal verticulata), asthenia, alopecia, depression, jaundice, and rigors.

The incidence of AST elevations was greater in the 200 and 240 mg FARESTON dose arms than in the tamoxifen arms. Higher doses of FARESTON were also associated with an increase in nausea.

Approximately 4% of patients were withdrawn for toxicity from the high-dose FARESTON treatment arms. Reasons for withdrawal included hypercalcemia, abnormal liver function tests, and one case each of toxic hepatitis, depression, dizziness, incoordination, ataxia, blurry vision, diffuse dermatitis, and a constellation of symptoms consisting of nausea, sweating, and tremor.

Post-marketing Experience

The following adverse reactions were identified during post approval use of FARESTON. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported during post approval use of FARESTON have been consistent with clinical trial experience. The most frequently reported adverse reactions related to FARESTON use since market introduction include hot flash, sweating, nausea, and vaginal discharge.

Read the Fareston (toremifene) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Drugs that Decrease Renal Calcium Excretion

Drugs that decrease renal calcium excretion, e.g., thiazide diuretics, may increase the risk of hypercalcemia in patients receiving FARESTON.

Agents that Prolong QT

The administration of FARESTON with agents that have demonstrated QT prolongation as one of their pharmacodynamic effects should be avoided. Should treatment with any of these agents be required, it is recommended that therapy with FARESTON be interrupted. If interruption of treatment with FARESTON is not possible, patients who require treatment with a drug that prolongs QT should be closely monitored for prolongation of the QT interval. Agents generally accepted to prolong QT interval include Class 1A (e.g., quinidine, procainamide, disopyramide) and Class III (e.g., amiodarone, sotalol, ibutilide, dofetilide) antiarrhythmics; certain antipsychotics (e.g., thioridazine, haloperidol); certain antidepressants (e.g., venlafaxine, amitriptyline); certain antibiotics (e.g., erythromycin, clarithromycin, levofloxacin, ofloxacin); and certain anti-emetics (e.g., ondansetron, granisetron). In patients at increased risk, electrocardiograms (ECGs) should be obtained and patients monitored as clinically indicated [see BOXED WARNING and WARNINGS AND PRECAUTIONS].

Effect of Strong CYP3A4 Inducers on Toremifene

Strong CYP3A4 enzyme inducers, such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital, St. John's Wort, lower the steady-state concentration of toremifene in serum.

Effect of Strong CYP3A4 Inhibitors on Toremifene

In a study of 18 healthy subjects, 80 mg toremifene once daily coadministered with 200 mg of ketoconazole twice daily increased the toremifene Cmax and AUC by 1.4- and 2.9-fold, respectively. N-demethyltoremifene Cmax and AUC were reduced by 56% and 20%, respectively.

The administration of FARESTON with agents that are strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) increase the steady-state concentration in serum and should be avoided. Grapefruit juice may also increase plasma concentrations of toremifene and should be avoided. Should treatment with any of these agents be required, it is recommended that therapy with FARESTON be interrupted. If interruption of treatment with FARESTON is not possible, patients who require treatment with a drug that strongly inhibits CYP3A4 should be closely monitored for prolongation of the QT interval [see BOXED WARNING and WARNINGS AND PRECAUTIONS].

Effect of Toremifene on CYP3A4 Substrates

In a study of 20 healthy subjects, 2 mg midazolam once daily (days 6 and 18) coadministered with toremifene as a 480 mg loading dose followed by 80 mg once daily for 16 days. Following coadministration on days 6 and 18 relevant increases in midazolam and α-hydroxymidazolam Cmax and AUC were not observed. Following coadministration on day 18 midazolam and α-hydroxymidazolam Cmax and AUC were reduced by less than 20%.

Clinically relevant exposure changes in sensitive substrates due to inhibition or induction of CYP3A4 by toremifene appear unlikely.

Effect of Toremifene on CYP2C9 Substrates

In a study of 20 healthy subjects, 500 mg tolbutamide once daily (days 7 and 19) coadministered with toremifene as a 480 mg loading dose followed by 80 mg once daily for 16 days. Following coadministration on days 7 and 19 plasma tolbutamide Cmax and AUC were increased by less than 30%. A reduction of similar magnitude was observed for hydroxytolbutamide and carboxytolbutamide Cmax and AUC.

Toremifene is a weak inhibitor of CYP2C9. Concomitant use of CYP2C9 substrates with a narrow therapeutic index such as warfarin or phenytoin with FARESTON should be done with caution and requires careful monitoring (e.g., substrate concentrations (if possible), appropriate laboratory markers, and signs and symptoms of increased exposure).

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Prolongation of the QT Interval

Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner [see CLINICAL PHARMACOLOGY]. 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 be avoided in patients with long QT syndrome. Caution should be exercised in patients with congestive heart failure, hepatic impairment and electrolyte abnormalities. Hypokalemia or hypomagnesemia must be corrected prior to initiating toremifene and these electrolytes should be monitored periodically during therapy. Drugs that prolong the QT interval should be avoided. In patients at increased risk, electrocardiograms (ECGs) should be obtained at baseline and as clinically indicated [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Hypercalcemia and Tumor Flare

As with other antiestrogens, hypercalcemia and tumor flare have been reported in some breast cancer patients with bone metastases during the first weeks of treatment with FARESTON. Tumor flare is a syndrome of diffuse musculoskeletal pain and erythema with increased size of tumor lesions that later regress. It is often accompanied by hypercalcemia. Tumor flare does not imply failure of treatment or represent tumor progression. If hypercalcemia occurs, appropriate measures should be instituted and, if hypercalcemia is severe, FARESTON treatment should be discontinued.

Tumorigenicity

Since most toremifene trials have been conducted in patients with metastatic disease, adequate data on the potential endometrial tumorigenicity of long-term treatment with FARESTON are not available. Endometrial hyperplasia has been reported. Some patients treated with FARESTON have developed endometrial cancer, but circumstances (short duration of treatment or prior antiestrogen treatment or premalignant conditions) make it difficult to establish the role of FARESTON. Endometrial hyperplasia of the uterus was observed in animals treated with toremifene [see Nonclinical Toxicology].

General

Patients with a history of thromboembolic diseases should generally not be treated with FARESTON. In general, patients with preexisting endometrial hyperplasia should not be given long-term FARESTON treatment. Patients with bone metastases should be monitored closely for hypercalcemia during the first weeks of treatment. Leukopenia and thrombocytopenia have been reported rarely; leukocyte and platelet counts should be monitored when using FARESTON in patients with leukopenia and thrombocytopenia.

Laboratory Tests

Periodic complete blood counts, calcium levels, and liver function tests should be obtained.

Use in Pregnancy

Based on its mechanism of action in humans and findings of increased pregnancy loss and fetal malformation in animal studies, FARESTON can cause fetal harm when administered to a pregnant woman. Toremifene caused embryo-fetal toxicities at maternal doses that were lower than the 60 mg daily recommended human dose on a mg/m² basis. There are no adequate and well-controlled studies in pregnant women using FARESTON. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use In Specific Populations].

Women of Childbearing Potential

FARESTON is indicated only in postmenopausal women. However, premenopausal women prescribed FARESTON should use effective non-hormonal contraception and should be apprised of the potential hazard to the fetus should pregnancy occur.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Conventional carcinogenesis studies in rats at doses of 0.12 to 12 mg/kg/day (approximately 1/50 to 2 times the daily maximum recommended human dose of 60 mg, on a mg/m² basis) for up to 2 years did not show evidence of carcinogenicity. Studies in mice at doses of 1.0 to 30.0 mg/kg/day (approximately 1/15 to 2 times the daily maximum recommended human dose of 60 mg, on a mg/m² basis) for up to 2 years revealed increased incidence of ovarian and testicular tumors and increased incidence of osteoma and osteosarcoma. The significance of the mouse findings is uncertain because of the different role of estrogens in mice and the estrogenic effect of toremifene in mice. An increased incidence of ovarian and testicular tumors in mice has also been observed with other human estrogen agonists/antagonists that have primarily estrogenic activity in mice. Endometrial hyperplasia of the uterus was observed in monkeys following 52 weeks of treatment at ≥ 1 mg/kg and in dogs following 16 weeks of treatment at ≥ 3 mg/kg with toremifene (approximately 1/3 and 1.4 times, respectively, the daily maximum recommended human dose of 60 mg, on a mg/m² basis).

Toremifene has not been shown to be mutagenic in in vitro tests (Ames and E. coli bacterial tests). Toremifene is clastogenic in vitro (chromosomal aberrations and micronuclei formation in human lymphoblastoid MCL-5 cells) and in vivo (chromosomal aberrations in rat hepatocytes).

Toremifene produced impairment of fertility and conception in male and female rats at doses ≥ 25.0 and 0.14 mg/kg/day, respectively (approximately 4 times and 1/50 the daily maximum recommended human dose of 60 mg, on a mg/m² basis). At these doses, sperm counts, fertility index, and conception rate were reduced in males with atrophy of seminal vesicles and prostate. In females, fertility and reproductive indices were markedly reduced with increased pre-and post-implantation loss. In addition, offspring of treated rats exhibited depressed reproductive indices. Toremifene produced ovarian atrophy in dogs administered doses ≥ 3 mg/kg/day (approximately 1.5 times the daily maximum recommended human dose of 60 mg, on a mg/m² basis) for 16 weeks. Cystic ovaries and reduction in endometrial stromal cellularity were observed in monkeys at doses ≥ 1 mg/kg/day (about 1/3 the daily maximum recommended human dose of 60 mg, on a mg/m² basis) for 52 weeks.

Use In Specific Populations

Pregnancy

Pregnancy Category D [see WARNINGS AND PRECAUTIONS.]

Based on its mechanism of action in humans and findings of increased pregnancy loss and fetal malformation in animal studies, FARESTON can cause fetal harm when administered to a pregnant woman. Toremifene caused embryo-fetal toxicities at maternal doses that were lower than the 60 mg daily recommended human dose on a mg/m² basis. There are no adequate and well-controlled studies in pregnant women using FARESTON. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

In animal studies, toremifene crossed the placenta and accumulated in the rodent fetus. Administration of toremifene to pregnant rats during organogenesis at doses of approximately 6% the daily maximum recommended human dose of 60 mg (on a mg/m² basis) resulted in signs of maternal toxicity and increased preimplantation loss, increased resorptions, reduced fetal weight, and fetal anomalies. Fetal anomalies include malformation of limbs, incomplete ossification, misshapen bones, ribs/spine anomalies, hydroureter, hydronephrosis, testicular displacement, and subcutaneous edema. Maternal toxicity may have contributed to these adverse embryo-fetal effects. Similar embryo-fetal toxicities occurred in rabbits that received toremifene at doses approximately 40% the daily recommended human dose of 60 mg (on a mg/m² basis). Findings in rabbits included increased preimplantation loss, increased resorptions, and fetal anomalies, including incomplete ossification and anencephaly.

Animal doses resulting in embryo-fetal toxicities were ≥ 1.0 mg/kg/day in rats and ≥ 1.25 mg/kg/day in rabbits.

In rodent models of fetal reproductive tract development, toremifene produced inhibition of uterine development in female pups similar to effects seen with diethylstilbestrol (DES) and tamoxifen. The clinical relevance of these changes is not known. Neonatal rodent studies have not been conducted to assess the potential for toremifene to cause other DES-like effects in offspring (i.e., vaginal adenosis). Vaginal adenosis in animals occurred following treatment with other drugs of this class and has been observed in women exposed to diethylstilbestrol in utero.

Nursing Mothers

It is not known if toremifene is excreted in human milk. Toremifene is excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from FARESTON, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

There is no indication for use of FARESTON in pediatric patients.

Geriatric Use

The pharmacokinetics of toremifene were studied in 10 healthy young males and 10 elderly females following a single 120 mg dose under fasting conditions. Increases in the elimination half-life (4.2 versus 7.2 days) and the volume of distribution (457 versus 627 L) of toremifene were seen in the elderly females without any change in clearance or AUC.

The median ages in the three controlled studies ranged from 60 to 66 years. No significant age-related differences in FARESTON effectiveness or safety were noted.

Renal Impairment

The pharmacokinetics of toremifene and N-demethyltoremifene were similar in normals and in patients with impaired kidney function.

Hepatic Impairment

The mean elimination half-life of toremifene was increased by less than twofold in 10 patients with hepatic impairment (cirrhosis or fibrosis) compared to subjects with normal hepatic function. The pharmacokinetics of Ndemethyltoremifene were unchanged in these patients. Ten patients on anticonvulsants (phenobarbital, clonazepam, phenytoin, and carbamazepine) showed a twofold increase in clearance and a decrease in the elimination half-life of toremifene.

Race

The pharmacokinetics of toremifene in patients of different races has not been studied.

Fourteen percent of patients in the North American Study were non-Caucasian. No significant race-related differences in FARESTON effectiveness or safety were noted.

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Lethality was observed in rats following single oral doses that were ≥ 1000 mg/kg (about 150 times the recommended human dose on a mg/m² basis) and was associated with gastric atony/dilatation leading to interference with digestion and adrenal enlargement.

Vertigo, headache, and dizziness were observed in healthy volunteer studies at a daily dose of 680 mg for 5 days. The symptoms occurred in two of the five subjects during the third day of the treatment and disappeared within 2 days of discontinuation of the drug. No immediate concomitant changes in any measured clinical chemistry parameters were found. In a study in postmenopausal breast cancer patients, toremifene 400 mg/m²/day caused dose-limiting nausea, vomiting, and dizziness, as well as reversible hallucinations and ataxia in one patient.

Theoretically, overdose may be manifested as an increase of antiestrogenic effects, such as hot flashes; estrogenic effects, such as vaginal bleeding; or nervous system disorders, such as vertigo, dizziness, ataxia, and nausea. There is no specific antidote and the treatment is symptomatic.

CONTRAINDICATIONS

Hypersensitivity to the Drug

FARESTON is contraindicated in patients with known hypersensitivity to the drug.

QT Prolongation, Hypokalemia, Hypomagnesemia

Toremifene should not be prescribed to patients with congenital/acquired QT prolongation (long QT syndrome), uncorrected hypokalemia, or uncorrected hypomagnesemia.

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

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., its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor.

Pharmacodynamics

Toremifene causes a decrease in the estradiol-induced vaginal cornification index in some postmenopausal women, indicative of its antiestrogenic activity. Toremifene also has estrogenic activity as shown by decreases in serum gonadotropin concentrations (FSH and LH).

Effects on Cardiac Electrophysiology

The effect of 20 mg, 80 mg, and 300 mg of toremifene on QT interval was evaluated in a double-blind, randomized study in healthy male subjects aged 18 to 45 years. The QT interval was measured at steady state of toremifene (Day 5 of dosing), including the time of peak plasma concentration (Tmax), at 13 time points (4 ECGs/time point) over 24 hours post dose in a time matched analysis. The 300 mg dose of toremifene (approximately five times the highest recommended dose 60 mg) was chosen because this dose produces exposure to toremifene that will cover the expected exposures that may result from potential drug interactions and hepatic impairment [see DRUG INTERACTIONS].

Dose and concentration-related increases in the QTc interval and T wave changes were observed (see Table 1). These effects are believed to be caused by toremifene and N-demethyltoremifene. Toremifene had no effects on heart rate, PR and QRS interval duration [see BOXED WARNING and WARNINGS AND PRECAUTIONS].

Table 1: QTc Prolongation in Healthy Male Volunteers

Treatment Arm Mean (90% CI) QTc, ms QTc > 60 ms (n, %) QTc > 500 ms (n, %)
Toremifene 20 mg (N = 47) 7 (0.9, 13.6) 0 0
Toremifene 80 mg (N = 47) 26 (21.1, 31.2) 2 (4.3%) 0
Toremifene 300 mg (N = 48) 65 (60.1, 69.2) 43 (89.6%) 5 (10.4%)

Pharmacokinetics

Absorption

Toremifene is well absorbed after oral administration and absorption is not influenced by food. Peak plasma concentrations are obtained within 3 hours. Toremifene displays linear pharmacokinetics after single oral doses of 10 to 680 mg. After multiple dosing, dose proportionality was observed for doses of 10 to 400 mg. Steady state concentrations were reached in about 4-6 weeks.

Distribution

Toremifene has an apparent volume of distribution of 580 L and binds extensively ( > 99.5%) to serum proteins, mainly albumin.

Metabolism

Toremifene is extensively metabolized, principally by CYP3A4 to N-demethyltoremifene which is also antiestrogenic but with weak in vivo antitumor potency. Serum concentrations of N-demethyltoremifene are 2 to 4 times higher than toremifene at steady state.

Following multiple dosing with toremifene in 20 healthy volunteers, plasma toremifene exposure was lower on Day 17 compared to Day 5 by approximately 14%. N-demethyltoremifene exposure was higher on Day 17 compared to Day 5 by approximately 80%. Based on these data and an in vitro induction study in human hepatocytes, auto-induction of CYP3A4 by toremifene is likely. The effect of auto-induction on efficacy was likely captured following prolonged dosing in the clinical studies.

Elimination

The plasma concentration time profile of toremifene declines biexponentially after absorption with a mean distribution half-life of about 4 hours and an elimination half-life of about 5 days. Elimination half-lives of major metabolites, N-demethyltoremifene and (Deaminohydroxy) toremifene, were 6 and 4 days, respectively. Mean total clearance of toremifene was approximately 5 L/h. Toremifene is eliminated as metabolites primarily in the feces, with about 10% excreted in the urine during a 1-week period. Elimination of toremifene is slow, in part because of enterohepatic circulation.

Renal insufficiency

The pharmacokinetics of toremifene and N-demethyltoremifene were similar in normals and patients with impaired kidney function.

Hepatic insufficiency

The mean elimination half-life of toremifene was increased by less than twofold in 10 patients with hepatic impairment (cirrhosis or fibrosis) compared to subjects with normal hepatic function. The pharmacokinetics of N-demethyltoremifene were unchanged in these patients. Ten patients on anticonvulsants (phenobarbital, clonazepam, phenytoin, and carbamazepine) showed a twofold increase in clearance and a decrease in the elimination half-life of toremifene.

Geriatric patients

The pharmacokinetics of toremifene were studied in 10 healthy young males and 10 elderly females following a single 120 mg dose under fasting conditions. Increases in the elimination half-life (4.2 versus 7.2 days) and the volume of distribution (457 versus 627 L) of toremifene were seen in the elderly females without any change in clearance or AUC. The median ages in the three controlled studies ranged from 60 to 66 years. No significant age-related differences in FARESTON effectiveness or safety were noted.

Food

The rate and extent of absorption of FARESTON are not influenced by food; thus FARESTON may be taken with or without food.

Race

The pharmacokinetics of toremifene in patients of different races has not been studied. Fourteen percent of patients in the North American Study were non-Caucasian. No significant race-related differences in FARESTON effectiveness or safety were noted.

Clinical Studies

Three prospective, randomized, controlled clinical studies (North American, Eastern European, and Nordic) were conducted to evaluate the efficacy of FARESTON for the treatment of breast cancer in postmenopausal women. The patients were randomized to parallel groups receiving FARESTON 60 mg (FAR60) or tamoxifen 20 mg (TAM20) in the North American Study or tamoxifen 40 mg (TAM40) in the Eastern European and Nordic studies. The North American and Eastern European studies also included high-dose toremifene arms of 200 and 240 mg daily, respectively. The studies included postmenopausal patients with estrogen-receptor (ER) positive or estrogen-receptor (ER) unknown metastatic breast cancer. The patients had at least one measurable or evaluable lesion. The primary efficacy variables were response rate (RR) and time to progression (TTP). Survival (S) was also determined. Ninety-five percent confidence intervals (95% CI) were calculated for the difference in RR between FAR60 and TAM groups and the hazard ratio (relative risk for an unfavorable event, such as disease progression or death) between TAM and FAR60 for TTP and S.

Two of the 3 studies showed similar results for all effectiveness endpoints. However, the Nordic Study showed a longer time to progression for tamoxifen (see table).

Clinical Studies

Study North American Eastern European Nordic
Treatment Group FAR60 TAM20 FAR60 TAM40 FAR60 TAM40
No. Patients 221 215 157 149 214 201
Responses
CR1 + PR2 14 + 33 11 + 30 7 + 25 3 + 28 19 + 48 19 + 56
RR3 (CR + PR)% 21.3 19.1 20.4 20.8 31.3 37.3
Difference in RR 2.2   -0.4   -6.0  
   95% CI4 for Difference in RR -5.8 to 10.2 -9.5 to 8.6 -15.1 to 3.1
Time to Progression (TTP)
Median TTP (mo.) 5.6 5.8 4.9 5.0 7.3 10.2
Hazard Ratio (TAM/FAR) 1.01   1.02   0.80  
   95% CI4 for Hazard Ratio (%) 0.81 to 1.26 0.79 to 1.31 0.64 to 1.00
Survival (S)
Median S (mo.) 33.6 34.0 25.4 23.4 33.0 38.7
Hazard Ratio (TAM/FAR) 0.94   0.96   0.94  
   95% CI4 for Hazard Ratio (%) 0.74 to 1.24 0.72 to 1.28 0.73 to 1.22
1CR = complete response; 2PR = partial response; 3RR = response rate; 4CI = confidence interval

The high-dose groups, toremifene 200 mg daily in the North American Study and 240 mg daily in the Eastern European Study, were not superior to the lower toremifene dose groups, with response rates of 22.6% and 28.7%, median times to progression of 5.6 and 6.1 months, and median survivals of 30.1 and 23.8 months, respectively. The median treatment duration in the three pivotal studies was 5 months (range 4.2-6.3 months).

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Vaginal bleeding has been reported in patients using FARESTON. Patients should be informed about this and instructed to contact their physician if such bleeding occurs.

FARESTON may harm the fetus and increase the risk for pregnancy loss [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].

Premenopausal women using FARESTON should use nonhormonal contraception during treatment and should be apprised of the potential hazard to the fetus should pregnancy occur [see WARNINGS AND PRECAUTIONS].

Patients with bone metastases should be informed about the typical signs and symptoms of hypercalcemia and instructed to contact their physician for further assessment if such signs or symptoms occur.

Patients who must take medications known to prolong the QT interval, or potent CYP3A4 inhibitors, should be informed of the effect of toremifene on QT interval. Toremifene has been shown to prolong the QTc interval in a dose-related manner [see BOXED WARNING, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Specific interactions with foods that inhibit CYP3A4, including grapefruit juice, have not been studied but may increase toremifene concentrations. Patients should avoid grapefruit products and other foods that are known to inhibit CYP3A4 during FARESTON treatment.

Certain other medicines, including over-the-counter medications or herbal supplements (such as St. John's Wort) and toremifene, can reduce concentrations of coadministered drugs [see DRUG INTERACTIONS].

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Vaginal bleeding has been reported in patients using FARESTON. Patients should be informed about this and instructed to contact their physician if such bleeding occurs.

FARESTON may harm the fetus and increase the risk for pregnancy loss [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].

Premenopausal women using FARESTON should use nonhormonal contraception during treatment and should be apprised of the potential hazard to the fetus should pregnancy occur [see WARNINGS AND PRECAUTIONS].

Patients with bone metastases should be informed about the typical signs and symptoms of hypercalcemia and instructed to contact their physician for further assessment if such signs or symptoms occur.

Patients who must take medications known to prolong the QT interval, or potent CYP3A4 inhibitors, should be informed of the effect of toremifene on QT interval. Toremifene has been shown to prolong the QTc interval in a dose-related manner [see BOXED WARNING, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Specific interactions with foods that inhibit CYP3A4, including grapefruit juice, have not been studied but may increase toremifene concentrations. Patients should avoid grapefruit products and other foods that are known to inhibit CYP3A4 during FARESTON treatment.

Certain other medicines, including over-the-counter medications or herbal supplements (such as St. John's Wort) and toremifene, can reduce concentrations of coadministered drugs [see DRUG INTERACTIONS].

Last reviewed on RxList: 6/3/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Fareston Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

TOREMIFENE - ORAL

(tor-EM-eh-feen)

COMMON BRAND NAME(S): Fareston

WARNING: Toremifene has caused very serious (possibly fatal) heart rhythm problems (QT prolongation in the EKG, torsades de pointes). Get medical help right away if any of these rare but serious side effects occur: fast/irregular heartbeat, seizures, severe dizziness, or fainting. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm. Before using toremifene, tell your doctor or pharmacist of all the drugs you take (see also Drug Interaction section) and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using toremifene safely.

USES: Toremifene is used in postmenopausal women to treat breast cancer that has spread to other parts of the body (metastatic breast cancer). It is usually used to treat cancer that needs estrogen, a female hormone, in order to grow (estrogen-receptor positive). Toremifene is a nonsteroidal antiestrogen that blocks the effects of estrogen in the breast tissue, thereby slowing or stopping the growth of cancer.

HOW TO USE: Take this medication by mouth with or without food, usually once daily or as directed by your doctor. Dosage is based on your medical condition and response to therapy.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.

Since this drug can be absorbed through the skin and lungs, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

Inform your doctor immediately if your condition worsens (e.g., you get new breast lumps).

Disclaimer

Fareston Consumer (continued)

SIDE EFFECTS: See also Warning section.

Hot flashes, sweating, nausea, vomiting, dry eyes, or dizziness may occur. If any of these side effects persist or worsen, notify your doctor promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: bone/joint/muscle pain or swelling, constipation, mental/mood changes (e.g., depression), trouble walking/clumsiness, swelling ankles/feet, unusual tiredness, vision changes (e.g., blurred vision, eye pain).

Toremifene may increase your risk of uterine cancer. Tell your doctor immediately if you develop changes in menstrual period, unusual vaginal bleeding/discharge or pain/pressure below your "belly button" (navel).

Tell your doctor immediately if any of these rare but very serious side effects occur: easy bleeding/bruising, signs of infection (e.g., fever, chills, persistent sore throat), persistent nausea/vomiting, severe abdominal/stomach pain, dark urine, yellowing eyes/skin.

Toremifene has rarely caused very serious (possibly fatal) blood clots in the lungs/legs, brain (stroke), and heart (heart attack). Seek immediate medical attention if you develop pain/swelling in the groin/calf, pain in the chest/jaw/left arm, confusion, fainting, severe sudden headache, slurred speech, sudden vision changes, shortness of breath, or weakness on one side of the body.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Fareston (toremifene) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: See also Warning section.

Before taking toremifene, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: bone cancer (metastases), blood disorders (e.g., anemia, low platelets), diabetes, history of stroke or other blood clots (e.g., in the legs, lungs), heart disease (e.g., heart attack, irregular heartbeat), high blood pressure, liver disease, long periods of sitting or lying down (e.g., immobility such as being bedridden), uterus problems such as endometrial hyperplasia.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Notify your doctor beforehand if you will be having surgery or will be confined to a chair/bed for a long time (e.g., a long plane flight).

During pregnancy, toremifene should be used only when clearly needed. It may harm an unborn baby. If you become pregnant or think you may be pregnant, inform your doctor immediately. Women of childbearing age should use 2 forms of birth control while using this medication. Discuss the use of birth control, the risks and benefits of this medication, and any other concerns about using this medication with your doctor.

It is not known if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

Disclaimer

Fareston Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: "blood thinners" (e.g., warfarin), estrogens, "water pills" (diuretics such as hydrochlorothiazide), drugs affecting liver enzymes that remove toremifene from your body (e.g., certain anti-seizure medications such as carbamazepine/clonazepam/phenobarbital/phenytoin, rifampin).

Many drugs besides toremifene may affect the heart rhythm (QT prolongation), including amiodarone, granisetron, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), and certain quinolone antibiotics (such as levofloxacin), among others.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood count, calcium levels, liver tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised April 2011. Copyright(c) 2011 First Databank, Inc.

Fareston Patient Information Including Side Effects

Brand Names: Fareston

Generic Name: toremifene (Pronunciation: tor EH mih feen)

What is toremifene (Fareston)?

Toremifene blocks estrogen from reaching cancer cells. Certain types of breast cancer require estrogen to grow.

Toremifene is used to slow the growth of metastatic breast cancer (cancer that has spread from the original tumor). Unlike chemotherapy, toremifene does not actually destroy cancer cells.

Toremifene may also be used for purposes not listed in this medication guide.

What are the possible side effects of toremifene (Fareston)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using toremifene and call your doctor at once if you have a serious side effect such as:

  • severe dizziness, fainting, fast or pounding heartbeats, seizure (convulsions);
  • nausea, vomiting, stomach pain, loss of appetite, constipation, increased thirst or urination, muscle pain or weakness, joint pain, confusion, and feeling tired or restless;
  • easy bruising, unusual bleeding, purple or red pinpoint spots under your skin;
  • vaginal bleeding or discharge;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
  • sudden numbness or weakness, especially on one side of the body;
  • chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;
  • pain, swelling, warmth, or redness in one or both legs;
  • blurred vision, eye pain, or seeing halos around lights;
  • jaundice (yellowing of the skin or eyes);
  • tremor; or
  • loss of movement in any part of your body.

Less serious side effects may include:

  • sweating, hot flashes;
  • mild nausea, constipation;
  • dizziness, spinning sensation;
  • depressed mood;
  • swelling in your hands or feet;
  • itching, skin discoloration; or
  • hair loss.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Fareston (toremifene) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about toremifene (Fareston)?

You should not use toremifene if you are allergic to it, or if you have a history of Long QT syndrome, or an uncontrolled electrolyte imbalance (low levels of potassium or magnesium in your blood).

Before you take toremifene, tell your doctor if you have endometrial hyperplasia (overgrowth of cells lining the uterus), bone cancer, or if you have ever had a blood clot.

Taking toremifene may increase your risk of developing endometrial hyperplasia, a condition that may lead to cancer of the uterus. Talk to your doctor about your individual risk.

Stop using toremifene and call your doctor at once if you have symptoms of a serious heart rhythm disorder (severe dizziness, fainting, fast or pounding heartbeats) or signs of high levels of calcium in your blood (nausea, vomiting, stomach pain, loss of appetite, constipation, increased thirst or urination, muscle pain or weakness, joint pain, confusion, and feeling tired or restless).

Side Effects Centers

Fareston Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking toremifene (Fareston)?

You should not use toremifene if you are allergic to it, or if you have:

  • a history of Long QT syndrome; or
  • an uncontrolled electrolyte imbalance (low levels of potassium or magnesium in your blood).

To make sure you can safely take toremifene, tell your doctor if you have any of these other conditions:

  • endometrial hyperplasia (overgrowth of cells lining the uterus);
  • bone cancer; or
  • if you have ever had a blood clot.

FDA pregnancy category D. Do not use toremifene if you are pregnant. It could harm the unborn baby. Use effective birth control if you are not past menopause, and tell your doctor if you become pregnant during treatment.

It is not known whether toremifene passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using toremifene.

Taking toremifene may increase your risk of developing endometrial hyperplasia, a condition that may lead to cancer of the uterus. Talk to your doctor about your individual risk.

How should I take toremifene (Fareston)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Toremifene is usually taken once a day. Follow your doctor's instructions.

You may take toremifene with or without food. Take the medicine at the same time each day.

To be sure this medicine is not causing harmful effects, your blood will need to be tested often. Your liver function may also need to be tested. Visit your doctor regularly.

Store at room temperature away from moisture, heat, and light.

Side Effects Centers

Fareston Patient Information including If I Miss a Dose

What happens if I miss a dose (Fareston)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Fareston)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking toremifene (Fareston)?

Grapefruit and grapefruit juice may interact with toremifene and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

What other drugs will affect toremifene (Fareston)?

Tell your doctor about all other medicines you use, especially:

  • arsenic trioxide (Trisenox);
  • isoniazid (for treating tuberculosis);
  • lithium (Eskalith, Lithobid);
  • St. John's wort;
  • tacrolimus (Prograf);
  • vitamin or mineral supplements that contain calcium or vitamin D;
  • warfarin (Coumadin, Jantoven);
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), levofloxacin (Levaquin), ofloxacin (Floxin), rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), telithromycin (Ketek), and others;
  • an antidepressant such as amitriptylline (Elavil, Vanatrip, Limbitrol), venlafaxine (Effexor), nefazodone, and others;
  • antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), voriconazole (Vfend), and others;
  • seizure medicine such as carbamazepine (Carbatrol, Tegretol), clonazepam (Klonopin), phenobarbital (Solfoton), or phenytoin (Dilantin);
  • a diuretic (water pill) such as chlorothiazide (Diuril), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Lopressor HCT, Vasoretic, Zestoretic), chlorthalidone (Hygroton, Thalitone), indapamide (Lozol), metolazone (Mykrox, Zaroxolyn), and others;
  • heart or blood pressure medication such as diltiazem (Cartia, Cardizem), nicardipine (Cardene), verapamil (Calan, Covera, Isoptin, Verelan), and others;
  • heart rhythm medicine such as amiodarone (Cordarone, Pacerone), dofetilide (Tikosyn), disopyramide (Norpace), ibutilide (Corvert), procainamide (Procan, Pronestyl), quinidine (Quin-G), sotalol (Betapace), and others;
  • HIV/AIDS medicine such as atazanavir (Reyataz), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), ritonavir (Norvir, Kaletra), and others;
  • medicine to prevent or treat nausea and vomiting such as granisetron (Kytril) or ondansetron (Zofran);
  • medicines to treat psychiatric disorders, such as haloperidol (Haldol), thioridazine (Mellaril), and others;
  • migraine headache medicine such as sumatriptan (Imitrex, Treximet) or zolmitriptan (Zomig); or
  • narcotic medication such as methadone (Methadose, Diskets, Dolophine).

This list is not complete and there are many other drugs that can interact with toremifene. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Where can I get more information?

Your pharmacist can provide more information about toremifene.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 7.01. Revision date: 5/17/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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