Major
Ciclosporin × diltiazem
Immunosuppressants. Calcineurin inhibitors×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Mechanism
Diltiazem blocks CYP3A4 and P-glycoprotein – cyclosporine clearance routes. Cyclosporine plasma levels rise by 50–100%. The combination is sometimes used intentionally in transplant patients to reduce cyclosporine dose (sparing effect), but requires monitoring.
Symptoms
Acute nephrotoxicity: rising creatinine, hypertension, tremor, headache. In transplant patients: accelerated graft function decline.
Management
For intentional sparing, reduce cyclosporine by 25–50% when starting diltiazem; check trough (C0) at days 3 and 7. For incidental combination: monitor cyclosporine and creatinine.