tacrolimus and rifampicin

Rifampicin is a potent inducer of cytochrome P450 3A4 and the efflux transporter P-glycoprotein. Tacrolimus is metabolised by CYP3A4 and is a substrate for P-glycoprotein. Induction of these pathways increases tacrolimus metabolism and reduces its intestinal absorption, leading to substantially lower blood concentrations.

Tacrolimus levels can fall below therapeutic range, significantly increasing the risk of acute graft rejection in organ transplant recipients. The effect is clinically important and can occur within days of starting rifampicin.

Avoid concomitant use where possible. If co-administration is unavoidable, increase the tacrolimus dose, guided by frequent trough level monitoring, and adjust therapy when rifampicin is stopped. Consider alternative antitubercular drugs such as rifabutin, which is a weaker inducer, if appropriate.

Established interaction, supported by clinical pharmacokinetic studies, case reports, and transplant guidelines. The magnitude of the effect is well documented.