esketamine + rifampin

Esketamine + rifampin refers to the concurrent use of **esketamine**, a non-competitive NMDA receptor antagonist primarily indicated for treatment-resistant depression, with **rifampin**, a potent inducer of cytochrome P450 enzymes (not itself an antidepressant but well known as an anti-tubercular agent and strong CYP inducer). Esketamine acts on the glutamatergic system to rapidly alleviate depressive symptoms, while rifampin is used primarily to treat infections such as tuberculosis. Co-administration is notable for pharmacokinetic interactions: rifampin induces hepatic metabolism (CYP2B6 and CYP3A4), resulting in decreased plasma concentrations and systemic exposure to esketamine by approximately 17–28%. However, this drug–drug interaction is not considered clinically significant; no dosage adjustment is recommended for esketamine when used with rifampin[1][3][4][6]. There is no established therapeutic rationale for the combination other than the possibility of their concurrent use in rare clinical scenarios—most pharmacological references address them as a drug–drug interaction rather than a fixed-dose combination product.