tazemetostat + rifampin

Tazemetostat + rifampin is a drug combination consisting of tazemetostat, a first-in-class, oral, selective inhibitor of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), and rifampin, a broad-spectrum antibiotic that is also a potent inducer of cytochrome P450 3A (CYP3A) enzymes. Tazemetostat is approved for the treatment of relapsed or refractory follicular lymphoma with EZH2 mutations or epithelioid sarcoma, whereas rifampin is used in the treatment of tuberculosis and other bacterial infections. This combination is specifically notable for a clinically significant pharmacokinetic drug-drug interaction: rifampin significantly reduces exposure to tazemetostat due to strong induction of CYP3A-mediated metabolism, decreasing tazemetostat plasma concentrations by approximately 84%. This interaction effectively contraindicates the coadministration of these drugs, as tazemetostat efficacy could be compromised[1][5][3][7].