Major
Dronedarone × tacrolimus
Class III antiarrhythmic×Calcineurin inhibitor (immunosuppressant)
Mechanism
Dronedarone blocks the P-glycoprotein transporter – the main tacrolimus clearance route. Tacrolimus plasma levels rise. Additional risk of additive QT prolongation.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
Avoid the combination. Alternative antiarrhythmics in transplant patients: a beta-blocker for rate control or catheter ablation. If unavoidable, reduce tacrolimus by 30% and check level at days 3 and 7.