Clarithromycin × Sirolimus

Sirolimus is cleared by CYP3A4 in the gut and liver and by P-glycoprotein. Clarithromycin strongly inhibits CYP3A4, so sirolimus blood levels rise. The sirolimus SmPC (Rapamune) lists clarithromycin among strong inhibitors it does not recommend combining with, and the FDA sirolimus label says to avoid the pair. The labels give no figure for this specific pair; for ketoconazole, another strong CYP3A4 inhibitor, the sirolimus SmPC reports a 10.9-fold rise in AUC.

Rising creatinine, thrombocytopenia, hepatitis within 5–7 days.

The combination is avoided. Clarithromycin is replaced by an antibiotic with less effect on sirolimus, usually azithromycin if the spectrum fits. If clarithromycin cannot be avoided, per the sirolimus SmPC trough sirolimus levels are measured during co-administration and after clarithromycin stops, and the sirolimus dose follows the result. The patient's clinical status and renal function are checked on the same schedule. A transplant specialist runs the regimen.