Use caution when prescribing clarithromycin with all statins. That according to an observational study from Canada. Clarithromycin has been shown to increase the toxicity of statins metabolized by CYP3A4, but even statins that are not metabolized by CYP3A4 are implicated in a new study. These include rosuvastatin (Crestor), fluvastatin (Lescol), and pravastatin (Pravachol). The study looked at Canadian health care databases and compared the use of clarithromycin (which also not only inhibits CYP3A4, but also inhibits liver enzymes that help metabolize all statins) with azithromycin (which does inhibit statin metabolism). Compared to use with azithromycin, use of clarithromycin, plus one of the three statins, increased the risk of hospitalization for kidney injury (relative risk [RR], 1.65; CI, 1.31-2.09), admission with hyperkalemia (RR, 2.17; CI, 1.22-3.86), rhabdomyolysis (RR, 2.27; CI, 0.86-5.96), and all-cause mortality (RR, 1.43; CI, 1.15-1.76). The incidence of these outcomes was small, with an absolute increase of < 1%, still statistically significant (CMAJ published online December 22, 2014, doi:10.1503/cmaj.140950). The FDA has recommended use of non-CYP3A4 metabolized statins as a safer alternative when taken with a CYP3A4 inhibitor, but, as this study points out, all statins may cause risk.