Critical
Clarithromycin × tacrolimus
Macrolide antibiotic×Calcineurin inhibitor (immunosuppressant)
Mechanism
Tacrolimus (a post-transplant immunosuppressant) is cleared via hepatic CYP3A4. Clarithromycin strongly inhibits CYP3A4. Tacrolimus plasma levels rise 4- to 5-fold. The narrow therapeutic window makes any rise clinically dangerous.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients, accelerated graft function decline.
Management
If the combination is unavoidable, reduce the tacrolimus dose by 50–66% immediately and check daily trough (C0) levels for the first 5–7 days. Better: replace clarithromycin with azithromycin (minimal CYP3A4 interaction, comparable spectrum).