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Co prescription of statins and antibiotics linked to extra deaths

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f3963 (Published 18 June 2013) Cite this as: BMJ 2013;346:f3963

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Evidence is growing of an important drug interaction between widely used statins and antibiotics. Clarithromycin and erythromycin inhibit the cytochrome P450 isoenzyme that metabolises atorvastatin, simvastatin, and lovastatin. Co-prescription of any combination of these statins and antibiotics increases blood concentrations of the statin, and extra side effects may follow, say researchers. In one large cohort from Canada, older adults taking an implicated statin alongside erythromycin or clarithromycin were significantly more likely to be admitted to hospital with rhabdomyolisis or acute kidney injury, and significantly more likely to die within 30 days than similar adults taking azithromycin instead. Azithromycin does not inhibit the cytochrome P450 isoenzyme.

The authors linked four of Ontario’s administrative databases to construct a cohort of 144 336 regular users of statins who also received a prescription for clarithromycin, erythromycin, or azithromycin between 2003 and 2010. Compared with azithromycin, a prescription for either of the other antibiotics was associated with one extra death in every 399 older adults treated, one extra acute kidney injury in every 499 treated, and one extra hospitalisation for rhabdomyolisis in every 5870 treated. These are small absolute increases, say the authors, but co-treatment is common. Atorvastatin is the most widely prescribed drug in Canada.

Analyses were extensively adjusted, and the results are in line with anecdotal reports of serious and sometimes lethal statin toxicity in older adults given erythromycin or clarithromycin. Prescribers should avoid the implicated combinations whenever possible, say the authors. All adults in this study were aged 65 or over.

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Cite this as: BMJ 2013;346:f3963