Letrovitae Drug Interactions

Metabolism of letrozole is partly mediated via CYP2A6 and CYP3A4. Cimetidine, a weak, unspecified inhibitor of CYP450 enzymes, did not affect the plasma concentrations of letrozole. The effect of potent CYP450 inhibitors is unknown.
There is no clinical experience to date on the use of letrozole in combination with estrogen or other anticancer agents, other than tamoxifen. Tamoxifen, other antiestrogens or estrogen-containing therapies may diminish the pharmacological action of letrozole. In addition, co-administration of tamoxifen with letrozole has been shown to substantially decrease plasma concentrations of letrozole. The concomitant administration of letrozole with tamoxifen, other antiestrogens or estrogens should be avoided.
In vitro, letrozole inhibits cytochrome P450 isozymes 2A6 and, moderately, 2C19, but the clinical relevance is unknown. Caution is therefore indicated when giving letrozole concomitantly with medicinal products whose elimination is mainly dependent on these isoenzymes and whose therapeutic index is narrow (eg phenytoin, clopidogrel).