Interaction between Tamoxifen and Diphenhydramine
Major
Metabolism
| ID | DDInter1744 and DDInter569 |
| Interaction | Chronic coadministration of potent or moderate CYP450 2D6 inhibitors including certain antidepressants may reduce the effectiveness of tamoxifen. The proposed mechanism is inhibition of tamoxifen bioactivation via CYP450 2D6 to endoxifen (4-hydroxy-N-desmethyltamoxifen), the active metabolite that may be responsible for much of tamoxifen's antiestrogenic activity. |
| Management | Based on available data, patients treated with tamoxifen should avoid the chronic use of potent CYP450 2D6 inhibitors such as fluoxetine, paroxetine, and quinidine whenever possible, and preferably also moderate inhibitors such as bupropion, duloxetine, and sertraline. If an antidepressant is required during treatment with tamoxifen, agents such as desvenlafaxine, fluvoxamine, milnacipran, levomilnacipran, mirtazapine, and venlafaxine may be considered, since they have mild to no effects on CYP450 2D6. Alternatively, aromatase inhibitors such as anastrozole, exemestane, and letrozole may be appropriate substitutes for tamoxifen in certain patients. Alternatively, aromatase inhibitors such as anastrozole, exemestane, and letrozole may be appropriate substitutes for tamoxifen in certain patients. |
| References | |
| Alternative for Tamoxifen |
L02B
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| Alternative for Diphenhydramine |
D04A
Doxepin (topical)
Cinchocaine (topical)
Lidocaine (topical)
Benzocaine (topical)
Tetracaine (ophthalmic)
Diphenhydramine (topical)
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.