Interactions between Clofazimine and Toremifene
1 drug interaction and 13 additional warnings found for the following 2 drugs:
- clofazimine
- toremifene
Drug interactions
Major drug interactions
Major:
clofazimine toremifene
Applies to: clofazimine and toremifene
Generally avoid
Toremifene has the potential to prolong the QT interval of the electrocardiogram in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The effect on the QT interval is dose- and concentration-dependent. In a placebo-controlled, parallel-design clinical trial, the mean QTc interval prolongation was 21 to 26 ms with 80 mg toremifene, and the 20 mg dose also affected the QTc interval. Abnormal new U waves were observed in 4.3% of subjects with the 80 mg dose. There are no data available for the therapeutic 60 mg dose. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, women and elderly patients may be more susceptible to the QT prolonging effects of drugs.
Management
Coadministration of toremifene with other drugs that can prolong the QT interval should generally be avoided. If treatment with other QT-prolonging drugs is required, interruption of toremifene therapy should be considered. Caution and clinical monitoring are recommended if concomitant use is unavoidable. In patients at increased risk, electrocardiograms (ECGs) are recommended at baseline and as clinically indicated. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References (4)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
- Cerner Multum, Inc. "Australian Product Information."
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
toremifene Food/Lifestyle
Applies to: toremifene
Generally avoid
Coadministration with grapefruit juice may theoretically increase the plasma concentrations of toremifene. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. Because toremifene is associated with dose- and concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.
Generally avoid
Due to their estrogenic effect, isoflavones present in soy such as genistein and daidzein may stimulate breast tumor growth and antagonize the antiproliferative action of toremifene. Supportive data are derived primarily from in vitro and animal studies. In vitro, low concentrations of these phytoestrogens have been found to promote DNA synthesis and reverse the inhibitory effect of tamoxifen on oestrogen-dependent breast cancer cell proliferation. In contrast, high concentrations of genistein greater than 10 microM/L have been found to enhance tamoxifen effects by inhibiting breast cancer cell growth. It is not known if these high concentrations are normally achieved in humans. Plasma concentrations below 4 microM/L have been observed in healthy volunteers given a soy diet for one month or large single doses of genistein. These concentrations are comparable to the low plasma concentrations associated with tumor stimulation reported in animals. In a study of 155 female breast cancer survivors with substantially bothersome hot flashes, a product containing 50 mg of soy isoflavones (40% to 45% genistein; 40% to 45% daidzein; 10% to 20% glycitein) taken three times a day was found to be no more effective than placebo in reducing hot flashes. No toxicity or recurrence of breast cancer was reported during the 9-week study period.
Management
Until more information is available, patients treated with toremifene should consider avoiding the consumption of grapefruit juice and soy-containing products. Patients should be advised to contact their physician if they experience vaginal bleeding or potential signs of blood clots such as chest pain, shortness of breath, sudden loss of vision, and pain, redness or swelling in an extremity. Patients should seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.
References (2)
- (2001) "Product Information. Fareston (toremifene)." Schering Corporation
- Therapeutic Research Faculty (2008) Natural Medicines Comprehensive Database. http://www.naturaldatabase.com
Disease interactions
12 potential interactions Applies to: 11 conditions, including Heart Failure, Diarrhea, Hypokalemia, Inflammatory Bowel Disease, and Thrombotic/Thromboembolic Disorder.
Diarrhea
Moderate:
clofazimine
Clofazimine has a moderate potential interaction with Diarrhea.
The use of clofazimine has been associated with severe abdominal symptoms including splenic infarction, bowel obstruction, and GI bleeding. Death has been reported following severe abdominal symptoms. Crystalline deposits have been found in the intestinal mucosa, liver, gallbladder, bile, spleen, adrenals, subcutaneous fat, mesenteric lymph nodes, muscles, bone and skin. Clofazimine should be administered cautiously in patients with GI problems such as abdominal pain and diarrhea.
Endometrial Dysplasia
Moderate:
toremifene
Toremifene has a moderate potential interaction with Endometrial Dysplasia.
Endometrial cancer, endometrial hyperplasia, hypertrophy, and uterine polyps have been reported in some patients treated with toremifene. Long-term use of toremifene has not been established in patients with preexisting endometrial hyperplasia. All patients should have baseline and annual gynecological examinations. In particular, patients at high risk of endometrial cancer should be closely monitored.
Heart Failure
Major:
toremifene
Toremifene has a major potential interaction with Heart Failure.
Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.
History, Thrombotic/Thromboembolic Disorder
Moderate:
toremifene
Toremifene has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.
Thromboembolic events such as thrombophlebitis and pulmonary embolism have been noted during toremifene therapy. Patients with an active or past history of thromboembolic events should generally not be administered toremifene.
Hypokalemia
Major:
toremifene
Toremifene has a major potential interaction with Hypokalemia.
Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.
Inflammatory Bowel Disease
Moderate:
clofazimine
Clofazimine has a moderate potential interaction with Inflammatory Bowel Disease.
The use of clofazimine has been associated with severe abdominal symptoms including splenic infarction, bowel obstruction, and GI bleeding. Death has been reported following severe abdominal symptoms. Crystalline deposits have been found in the intestinal mucosa, liver, gallbladder, bile, spleen, adrenals, subcutaneous fat, mesenteric lymph nodes, muscles, bone and skin. Clofazimine should be administered cautiously in patients with GI problems such as abdominal pain and diarrhea.
Liver Disease
Moderate:
clofazimine
Clofazimine has a moderate potential interaction with Liver Disease.
Use of clofazimine should be avoided in patients with hepatic dysfunction (Child-Pugh A, B, or C).
Moderate:
toremifene
Toremifene has a moderate potential interaction with Liver Disease.
Hepatotoxicity, hepatitis, and non-alcoholic fatty liver disease have been reported in clinical trials and postmarketing with toremifene. Liver function tests should be performed periodically. Caution is advised in patients with any hepatic impairment.
Long QT Syndrome
Major:
toremifene
Toremifene has a major potential interaction with Long QT Syndrome.
Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.
Magnesium Imbalance
Major:
toremifene
Toremifene has a major potential interaction with Magnesium Imbalance.
Toremifene has shown to prolong the QTc interval in a dose and concentration related manner, which can result in Torsade de Pointes (ventricular tachycardia), syncope, seizure, and/or death. Toremifene should not be prescribed to patients with congenital or acquired QT prolongation, uncorrected hypokalemia or uncorrected hypomagnesemia. Caution is advised in patients with congestive heart failure, and patients taking other drugs that can prolong the QT interval.
Renal Dysfunction
Moderate:
clofazimine
Clofazimine has a moderate potential interaction with Renal Dysfunction.
Clofazimine should be used with caution in patients with severe renal dysfunction. No dose adjustments are recommended in patients with mild to moderate renal dysfunction.
Thrombotic/Thromboembolic Disorder
Moderate:
toremifene
Toremifene has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.
Thromboembolic events such as thrombophlebitis and pulmonary embolism have been noted during toremifene therapy. Patients with an active or past history of thromboembolic events should generally not be administered toremifene.
Report options
More resources
clofazimine
A total of 385 drugs are known to interact with clofazimine.
- Clofazimine is in the drug class leprostatics.
- Clofazimine is used to treat the following conditions:
toremifene
A total of 432 drugs are known to interact with toremifene.
- Toremifene is in the following drug classes: hormones/antineoplastics, selective estrogen receptor modulators.
- Toremifene is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.