Interactions between Menthol topical and Toremifene
1 drug interaction and 9 additional warnings found for the following 2 drugs:
- menthol topical
- toremifene
Drug interactions
Minor drug interactions
Minor:
menthol topical toremifene
Applies to: menthol topical and toremifene
Coadministration with orally administered menthol may decrease plasma concentrations of drugs that are substrates of the CYP450 3A4 and/or CYP450 2C9 isoenzymes. The proposed mechanism is increased clearance due to menthol-mediated induction of CYP450 3A4 and CYP450 2C9. In vivo data suggests that concomitant administration of oral menthol reduced the systemic exposure (AUC) of triazolam (a CYP450 3A4 substrate) by 40%, and phenytoin (a CYP450 2C9 substrate) by 20%. Until further data are available, no specific precautions are recommended.
References (4)
- (2024) "Product Information. Advil Targeted Relief (camphor/capsicum/menthol/methyl salicylate topical)." Haleon
- Hoshino M (2015) "Effects of menthol on the pharmacokinetics of triazolam and phenytoin." Biol Pharm Bull, 38, p. 454-60
- Hoshino M (2014) "Menthol reduces the anticoagulation effect of warfarin by cytochrome p450 2C expression." Eur J Pharm Sci, 56, p. 92-101
- (2019) "Product Information. Radian B Muscle Rub (camphor/capsicum/menthol/meth salic top)." Thornton & Ross Ltd
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
8 potential interactions Applies to: 8 conditions, including Heart Failure, Hypokalemia, Thrombotic/Thromboembolic Disorder, Liver Disease, and Long QT Syndrome.
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.
Liver Disease
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.
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.
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More resources
menthol topical
A total of 364 drugs are known to interact with menthol topical.
- Menthol topical is in the drug class topical rubefacient.
- Menthol topical 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
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