Clarithromycin × Ciclosporin

Cyclosporine (an immunosuppressant used after solid-organ transplantation and in severe autoimmune disease) is cleared through hepatic CYP3A4 and actively transported by P-glycoprotein. Clarithromycin inhibits both the enzyme and the transporter. Cyclosporine plasma levels rise 2- to 4-fold. The narrow therapeutic window (minimal margin between therapeutic and toxic dose) makes any concentration rise clinically dangerous.

Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Hypertension, headache, tremor. In transplant patients, accelerated graft function decline. Symptoms appear within a few days of concurrent dosing.

Avoid the combination. Replace clarithromycin with azithromycin – minimal CYP3A4 and P-glycoprotein interaction with comparable activity. If clarithromycin is essential, reduce the cyclosporine dose by 30–50% immediately, measure cyclosporine trough or C2 levels (per the transplant centre protocol) every 2–3 days, and monitor creatinine.