Drug interaction between maribavir and rifampin: a case report

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in immunocompromised patients, particularly transplant recipients. The emergence of drug-resistant CMV strains and the toxicities of conventional antiviral therapies like ganciclovir highlight the need for novel treatments. Maribavir, a benzimidazole riboside, offers an alternative due to its unique mechanism of action-selectively inhibiting the CMV UL97 protein kinase, which is essential for viral replication. It is effective against wild-type and ganciclovir-resistant CMV strains. Pharmacologically, maribavir is rapidly absorbed, highly protein-bound (>98%), and metabolized via CYP3A4, leading to a short half-life (4-5 hours) and twice-daily dosing. However, CYP3A4-mediated drug-drug interactions (DDIs)-particularly with inducers like rifampin-pose a risk, as rifampin reduces maribavir's C_max, AUC, and C_trough by 39%, 60%, and 82%, respectively, potentially compromising efficacy. A 47-year-old renal transplant patient with ganciclovir-resistant CMV and concurrent tuberculosis required maribavir and rifampin. Despite the DDI, dose escalation to 800 mg TID (guided by therapeutic drug monitoring) achieved adequate C_trough, controlling CMV viremia without adverse effects. This case suggests that dose adjustment with close monitoring may mitigate DDIs when coadministration is unavoidable. Further studies are needed to validate this approach, given the increased cost and potential for resistance.