Major
Rifampicin × tacrolimus
Antituberculous antibiotic×Calcineurin inhibitor (immunosuppressant)
Mechanism
Rifampicin is the strongest known CYP3A4, CYP2C9, and P-glycoprotein inducer. Tacrolimus is a CYP3A4 and P-gp substrate with a narrow therapeutic window (target trough 5–15 ng/mL). Tacrolimus exposure drops 3- to 7-fold; acute graft rejection risk is high.
Symptoms
Graft rejection on biochemistry and biopsy. There are no symptoms from reduced tacrolimus exposure itself – the loss of immunosuppression is silent.
Management
Avoid the combination. For tuberculosis in transplant recipients use rifampicin-free regimens (isoniazid + ethambutol + pyrazinamide) or rifabutin (much weaker CYP3A4 induction). If rifampicin is essential – empirically increase tacrolimus 2- to 5-fold with trough monitoring every 2–3 days for the first 2 weeks, then weekly.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.