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Drug Interactions between dexamethasone and tamoxifen

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

dexAMETHasone tamoxifen

Applies to: dexamethasone and tamoxifen

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of tamoxifen, which is metabolized by the isoenzyme. In ten healthy subjects, the potent CYP450 3A4 inducer rifampin (600 mg orally once a day for 5 days) decreased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and elimination half-life of tamoxifen (80 mg single oral dose) by 55%, 86% and 44%, respectively, compared to placebo. The AUC of the active N-demethyl metabolite decreased by 62% and Cmax increased by 46%, suggesting enhanced presystemic metabolism in the intestine. Aminoglutethimide has also been reported to significantly increase the clearance of tamoxifen by more than 3-fold. Coadministration of another CYP450 3A4 inducer, bexarotene, resulted in a 35% decrease in plasma concentrations of tamoxifen. The extent to which other CYP450 3A4 inducers may affect tamoxifen is unknown.

MANAGEMENT: In general, agents without CYP450 3A4-inducing activity are preferable in patients treated with tamoxifen, particularly if these agents are to be used for a prolonged period. Otherwise, pharmacologic response to tamoxifen should be monitored closely whenever an inducing agent is added to or withdrawn from therapy, and the tamoxifen dosage adjusted if necessary.

References

  1. Lien EA, Anker G, Lonning PE, et al. "Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide." Cancer Res 50 (1990): 5851-7
  2. Kivisto KT, Villikka K, Nyman L, Anttila M, Neuvonen PJ "Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin." Clin Pharmacol Ther 64 (1998): 648-54
  3. "Product Information. Targretin (bexarotene)." Ligand Pharmaceuticals PROD (2001):
  4. Biochem Pharmacol "Variable contribution of cytochromes P450 2D6, 2C9, and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes." Biochem Pharmacol 53 (1997): 171-8
View all 4 references

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Drug and food interactions

Moderate

tamoxifen food

Applies to: tamoxifen

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 tamoxifen. 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 estrogen-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.

Green tea does not appear to have significant effects on the pharmacokinetics of tamoxifen or its primary active metabolite, endoxifen. In a study consisting of 14 patients who have been receiving tamoxifen treatment at a stable dose of 20 mg (n=13) or 40 mg (n=1) once daily for at least 3 months, coadministration with green tea supplements twice daily for 14 days resulted in no significant differences in the pharmacokinetics of either tamoxifen or endoxifen with respect to peak plasma concentration (Cmax), systemic exposure (AUC), and trough plasma concentration (Cmin) compared to administration of tamoxifen alone. The combination was well tolerated, with all reported adverse events categorized as mild (grade 1) and none categorized as serious or severe (grade 3 or higher) during the entire study. Although some adverse events such as headache, polyuria, gastrointestinal side effects (e.g., constipation, dyspepsia), and minor liver biochemical disturbances were reported more often during concomitant treatment with green tea, most can be attributed to the high dose of green tea used or to the caffeine in green tea. The green tea supplements used were 1000 mg in strength and contained 150 mg of epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea. According to the investigators, the total daily dose of EGCG taken by study participants is equivalent to the amount contained in approximately 5 to 6 cups of regular green tea. However, it is not known to what extent the data from this study may be applicable to other preparations of green tea such as infusions, since the bioavailability of EGCG and other catechins may vary between preparations.

MANAGEMENT: Until more information is available, patients treated with tamoxifen may consider avoiding or limiting the consumption of soy-containing products. Consumption of green tea and green tea extracts during tamoxifen therapy appears to be safe.

References

  1. Therapeutic Research Faculty "Natural Medicines Comprehensive Database. http://www.naturaldatabase.com" (2008):
  2. Braal CL, Hussaarts KGAM, Seuren L, et al. "Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen." Breast Cancer Res Treat 184 (2020): 107-13

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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