Statin-induced rhabdomyolysis from azithromycin interaction in a patient with heterozygous SLCO1B1 polymorphism.

Publisher: Country of Publication: England NLM ID: 8704308 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2710 (Electronic) Linking ISSN: 02694727 NLM ISO Abbreviation: J Clin Pharm Ther Subsets: MEDLINE

Publication: Oxford : Wiley-Blackwell Pub.
Original Publication: Oxford : Blackwell Scientific Publications, c1987-

Anti-Bacterial Agents/*pharmacology ; Azithromycin/*pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects ; Hypolipidemic Agents/*adverse effects ; Liver-Specific Organic Anion Transporter 1/*genetics ; Rhabdomyolysis/*chemically induced; Aged ; Cytochrome P-450 CYP3A Inhibitors/pharmacology ; Drug Interactions ; Humans ; Male ; Polymorphism, Single Nucleotide

What Is Known and Objective: Unlike other macrolide antibiotics, azithromycin is considered safe to co-prescribe with simvastatin. We aim to elucidate the mechanism of a rare azithromycin-simvastatin interaction.
Case Description: We report a case of simvastatin-induced rhabdomyolysis caused by an azithromycin drug interaction in a patient with heterozygous SLCO1B1 loss-of-function polymorphism. We propose a dual-hit mechanism for this drug-drug-genome interaction. Azithromycin mildly inhibits simvastatin's CYP 3A4 hepatic metabolism, and the SLCO1B1 polymorphism reduces simvastatin hepatic uptake. The combination increases simvastatin serum concentrations significantly, inducing rhabdomyolysis.
What Is New and Conclusion: Patients with statin-induced myopathy associated with non-classic CYP inhibitors should be considered for genetic testing and alternative statins with less risk of future interactions.
(© 2020 John Wiley & Sons Ltd.)

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Keywords: azithromycin; drug interaction; macrolide; pharmacogenetics; rhabdomyolysis; simvastatin; statin

0 (Anti-Bacterial Agents)
0 (Cytochrome P-450 CYP3A Inhibitors)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (Hypolipidemic Agents)
0 (Liver-Specific Organic Anion Transporter 1)
0 (SLCO1B1 protein, human)
83905-01-5 (Azithromycin)

Date Created: 20201205 Date Completed: 20211206 Latest Revision: 20211214

20240829

10.1111/jcpt.13327

33277702