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Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction

Clinical Pharmacist, Pharmacy Department, Lutheran Hospital, Fort Wayne, IN

Ronald J Jones, PharmD

Associate Professor of Clinical Pharmacy, College of Pharmacy, Ohio Northern University, Ada, OH; Clinical and Practitioner/Educator, Pharmacy Department, Lutheran Hospital

Gordon H Bokhart, PharmD

Clinical Coordinator, Pharmacy Department, Lutheran Hospital

Reprints: Ronald J Jones PharmD, Pharmacy Department, Lutheran Hospital, 7950 W. Jefferson Blvd., Fort Wayne, IN 46804-4160, FAX 260/435-7609, E-mail r-jones{at}onu.edu

OBJECTIVE: To report rhabdomyolysis (RML) causing third-degree atrioventricular block secondary to a possible interaction between atorvastatin, esomeprazole, and clarithromycin.

CASE SUMMARY: A 51-year-old white woman presented to the emergency department with severe weakness, near syncope, shortness of breath, and chest pain. On admission, her electrocardiogram demonstrated bradycardia (40 beats/min) and third-degree heart block. A creatine kinase (CK) level was >7000 U/L. Her medication history was significant for long-term use of atorvastatin (>1 y), a 6-week history of esomeprazole use, and three 500-mg doses of clarithromycin just prior to admission. Her symptoms of weakness, shortness of breath, and chest pain coincided with starting the esomeprazole. During her hospitalization, the woman required pacemaker placement and her CK continued to rise to >40 000 U/L. Screening for other causes of RML, such as thyrotoxicosis, infection, and immune or hepatic diseases, was negative. She gradually improved over a 26-day hospitalization.

DISCUSSION: This is a case of RML resulting in third-degree atrioventricular blockade. An objective causality assessment of the adverse reaction via the Naranjo probability scale revealed a probable association with atorvastatin and a possible association with esomeprazole and clarithromycin. The pharmacokinetic profiles of these agents suggest that a possible contribution to this reaction was P-glycoprotein (PGP) inhibition by esomeprazole altering atorvastatin's normally significant first-pass clearance.

CONCLUSIONS: PGP drug interactions with atorvastatin and other hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may be associated with unreported risks for RML. Further investigation into PGP impact on HMG-CoA appears warranted.

Key Words: atorvastatin, atrioventricular blockade, clarithromycin, esomeprazole, P-glycoprotein, rhabdomyolysis

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