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Erythromycin-Induced Carbamazepine Toxicity: A Continuing Problem

Carl E. Stafstrom, MD, PhD; Virinder Nohria, MD, PhD; Heidi Loganbill, MD; Robert Nahouraii, MD; Rose-Mary Boustany, MD; G. Robert DeLong, MD
Arch Pediatr Adolesc Med. 1995;149(1):99-101. doi:10.1001/archpedi.1995.02170130101025.
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Carbamazepine is frequently prescribed for the control of generalized and partial seizures in children. Erythromycin is a macrolide antibiotic often used in children with minor bacterial infections, especially in those with an allergy to penicillin. Multiple case reports1-7 and pharmacokinetic studies in humans and animals8-10 have established that erythromycin causes carbamazepine toxicity when the two drugs are administered concurrently. Erythromycin interferes with liver microsomal metabolism of carbamazepine, causing decreased carbamazepine clearance, an elevated serum carbamazepine level, and clinical toxicity. Erythromycin-induced carbamazepine toxicity usually manifests as drowsiness, lethargy, ataxia, vomiting, and nystagmus. More serious adverse effects have included heart block11 and severe liver and kidney failure.12

Despite an extensive literature about the adverse interaction between these two drugs, physicians continue to prescribe both medications. During a recent 6-month period, we encountered three cases of carbamazepine toxicity in children for whom erythromycin or clarithromycin (methylerythromycin, a new macrolide


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