Description
Interaction with other medicinal products and other types of interactions
Metabolism of letrozole is partly performed with the participation of CYP2A6 and CYP3A4. Thus, the systemic withdrawal of letrozole may be affected by drugs affecting CYP3A4 and CYP2A6 enzymes. Apparently, metabolism of letrozole has low affinity with CYP3A4, because this enzyme is not saturated at concentrations 150 times higher than concentrations of letrozole that are found in plasma during the equilibrium state under typical clinical conditions.
It was reported that in concomitant use of letrozole with cimetidine and warfarin no clinically significant interaction was observed, despite the fact that cimetidine is known to be an inhibitor of one of the isoenzymes of the cytochrome P450 system involved in the metabolism of letrozole in vitro.
No clinically significant interactions between letrozole and other drugs that are frequently used are known (e.g. benzodiazepine, barbiturates, NSAIDs such as diclofenac sodium, ibuprofen, paracetamol, furosemide, omeprazole).
To date, there is no clinical experience with letrozole in combination with estrogens or anticancer drugs other than tamoxifen. Tamoxifen, other anti-estrogens or estrogenic drugs may offset the pharmacological effect of letrozole. In addition, it is proved that in case of concomitant use of tamoxifen and letrozole plasma concentrations of letrozole are significantly reduced. Concomitant use of letrozole with tamoxifen, estrogen antagonists or estrogens should be avoided.
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