Moderate
Amlodipine × tacrolimus
Calcium channel blockers (dihydropyridines)×Calcineurin inhibitor (immunosuppressant)
Mechanism
Tacrolimus and amlodipine are both CYP3A4 substrates competing for the enzyme. Tacrolimus plasma levels may rise.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft decline.
Management
The combination is acceptable in post-transplant patients with hypertension. Check tacrolimus trough (C0) 1 week after starting or changing amlodipine. Alternative: an ARB or α-blocker (no CYP3A4 dependence).