Ovalia Drug Interactions

Metabolism of letrozole is partly mediated via CYP2A6 and CYP3A4. Clinical interaction studies with cimetidine and warfarin indicated that the co-administration of letrozole with these drugs does not result in clinically significant drug interactions, even though cimetidine is a known weak inhibitor of one of the cytochrome P450 isoenzymes capable of metabolising letrozole in vitro.
There was no evidence of other clinically relevant interaction in patients receiving other commonly prescribed drugs (e.g. benzodiazepines; barbiturates; NSAIDs such as diclofenac sodium, ibuprofen; paracetamol; furosemide; omeprazole).
There is no clinical experience to date on the use of letrozole in combination with oestrogens or other anticancer agents, other than tamoxifen. Tamoxifen, other anti-oestrogens or oestrogen-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. Co-administration of letrozole with tamoxifen, other anti-oestrogens or oestrogens should be avoided.
Letrozole inhibits in vitro the cytochrome P450 isoenzymes 2A6 and moderately 2C19, however, CYP2A6 does not play a major role in drug metabolism. In in vitro experiments, letrozole was not able to substantially inhibit the metabolism of diazepam (a substrate of CYP2C19) at concentrations approximately 100-fold higher than those observed in plasma at steady-state. Thus, clinically relevant interactions with CYP2C19 are unlikely to occur. Nevertheless, caution should be used in the concomitant administration of drugs whose disposition is mainly dependent on these isoenzymes and whose therapeutic index is narrow (e.g phenytoin, clopidogrel).