cyclosporine and rifampicin

Rifampicin induces hepatic and intestinal CYP3A4 and P-glycoprotein, which are the main enzymes and transporters responsible for cyclosporine metabolism and efflux. This induction increases the first-pass metabolism and systemic clearance of cyclosporine, leading to markedly reduced blood concentrations.

Co-administration can cause a clinically significant reduction in cyclosporine exposure, potentially leading to subtherapeutic immunosuppression. This increases the risk of acute and chronic organ rejection in transplant recipients, or loss of therapeutic effect in autoimmune conditions.

Avoid co-prescription where possible. If concurrent use is necessary, increase the cyclosporine dose and monitor whole-blood trough levels frequently, adjusting the dose as needed. After stopping rifampicin, reduce the cyclosporine dose and monitor closely to avoid toxicity.

This interaction is well-established and consistently reported in clinical studies and product monographs. Rifampicin is a potent inducer of CYP3A4 and P-gp; multiple case reports and pharmacokinetic studies show marked reductions in cyclosporine levels.