Erythromycin is a macrolide antibiotic that inhibits bacterial protein synthesis and is effective against the same organisms as penicillin G.
The drug is commonly used to treat community-acquired pulmonary infections in penicillin-allergic patients. Erythromycin also has prokinetic effects on the gastrointestinal system.
At low doses, erythromycin prokinetic agent induces activity in the gastric antrum, which propagates to the small intestines. At higher doses, erythromycin induces a prolonged period of antral activity by stimulating motilin receptors to accelerate gastric emptying.
Although transplant recipients frequently suffer from opportunistic bacterial infections and/or gastrointestinal dysmotility, erythromycin should not be given to recipients taking FK506 (tacrolimus, Prograf) or cyclosporine.
FK506 is structurally similar to erythromycin prokinetic agent. It is a macrolide that exhibits strong immunosuppressive properties by inhibiting the transcription of interleukin-2 during T-cell activation. Like FK506, cyclosporine is a calcineurin inhibitor and both drugs are routinely given for prophylaxis of organ rejection.
Both FK506 and cyclosporine have narrow therapeutic windows and both require daily lab draws in the perioperative period to ensure efficacious drug levels. Both drugs are metabolized by the liver’s P450 CYP 3A4 enzyme pathway (the most common pathway for drug metabolism).
Erythromycin prokinetic agent is a strong inhibitor of this pathway and concurrent administration of erythromycin and FK506 (in particular) or cyclosporin can result in elevated immunosuppression drug levels and severe toxicity even after one or two doses of erythromycin. This toxicity can manifest as severe renal dysfunction, tremors, seizures, brittle diabetes, or corneal ulcerations.
Other common intensive care unit medications apart from erythromycin prokinetic agent can also induce the P450 CYP 3A4 system and thus decrease serum levels of FK506 and cyclosporine.
These include phenobarbital, carbamazepine, phenytoin, and rifampin. Drugs metabolized through this pathway should always be double-checked for drug interactions.