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Certain statin and antibiotic combinations appear to increase the risk of serious statin side-effects

Posted Aug 30 2013 1:56pm

Statin drugs are promoted for their ability to prevent heart attacks and strokes but, as with all medications, they are not without risk either. They can, for example, be toxic to the muscles and kidneys and, in extreme circumstances, can cause muscle breakdown known as ‘rhabdomyolysis’ as well as cause critical injury to the kidneys.

The risk of toxic effects of statins will depend on individual susceptibility (some people are more prone to issues than others), but also the level of statin in the bloodstream. The latter is to a degree dependent on the dose of statin (higher dosages mean generally higher blood levels), but also the speed at which the statin is metabolised.

Some of the most common statins – atorvastatin (Lipitor), simvastatin (Zocor) and lovastatin (Mevacor) – are metabolised through the action of a collection of enzymes referred to as ‘cytochrome P450’. The more efficiently cytochrome P450 functions, the more readily these statins are deactivated, and the lower levels of these drugs will tend to be in the bloodstream at a given dosage. However, if cytochrome P450 is inhibited in any way, then levels of these statins can rise. With that rises the risk of toxicity.

Certain antibiotics – specifically erythromycin and clarithromycin – are known to inhibit cytochrome P450, and a recent paper in the Annals of Internal Medicine has raised concerns about whether taking these drugs along with atorvastatin, simvastatin or lovastatin may increase the risk of side effects such as rhabdomyolysis or kidney injury [1].

In this study, researchers assessed the risk of these issues in people taking one of these statins in combination with either erythromycin or clarithromycin, and compared it to risks in individuals who were taking another antibiotic (azithromycin) that does not affect cytochrome P450.

It turned out that the suspect combinations of drugs were associated with a more than doubling in risk of rhabdomyolysis, and a 78 per cent increased risk of acute kidney damage. Overall risk of death was 56 per cent higher too.

This sort of study is ‘epidemiological’ in nature, and cannot tell us that certain drug combinations are harmful, only that they are associated with worse health outcomes. However, given what we know about the potential side-effects of statins and the theoretical ability of specific antibiotics to increase statin toxicity, I’d say there is genuine cause for concern here. The authors of the study suggest that the suspect drug combinations should be avoided wherever possible.

It’s probably a good idea for individuals taking atorvastatin, simvastatin or lovastatin to be vigilant regarding their interaction with the antibiotics erythromycin and clarithromycin. They may need to make their doctor aware of this potential interaction as the likelihood, I think, is that they’ll be unaware of it.

References:

1. Patel AM, et al. Statin Toxicity From Macrolide Antibiotic Coprescription: A Population-Based Cohort Study. Ann Intern Med 2013;158(12):869-876

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