A 55-year-old client takes warfarin for atrial fibrillation, simvastatin for hyperlipidemia, and is now prescribed erythromycin 500 mg PO four times daily for a skin infection. Which client report should the nurse address as a priority drug interaction concern?

Erythromycin is a macrolide that is a strong CYP3A4 inhibitor (clarithromycin is also strong; azithromycin is weak). It is also a motilin receptor agonist, producing significant nausea, vomiting, abdominal cramping, and diarrhea — sometimes used at low dose as a prokinetic. The clinical priorities in this scenario: (1) warfarin — erythromycin inhibits CYP3A4 and 1A2 metabolism, raising INR and bleeding risk; bruising and bleeding are warning signs; anticipate INR monitoring; (2) simvastatin — strong CYP3A4 substrate; erythromycin elevates simvastatin levels markedly, causing myopathy and rhabdomyolysis; new muscle pain, weakness, dark urine require holding the statin and CK measurement; (3) GI motilin effect — severe cramping, nausea, vomiting, diarrhea common; can be limiting; report and titrate; (4) QT prolongation as macrolide class effect; (5) hepatotoxicity rare but possible; (6) several other interactions — carbamazepine, theophylline, cyclosporine, and many others — require pharmacist review. Nursing actions: communicate with prescriber and pharmacy, anticipate INR check, possible statin hold or switch to a non-CYP3A4-inhibiting antibiotic, education on bleeding and myopathy signs, supportive care for GI side effects.

Erythromycin = strong CYP3A4 inhibitor + motilin agonist. Warfarin and statin interactions are highest priority. Switch to a non-CYP3A4 alternative if possible.