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In older people who are taking statins that are not metabolised by cytochrome p450 3A4 (CYP3A4), concurrent clarithromycin “is associated with a modest increase in the number of deaths and hospital admissions because of adverse events that may reflect statin toxicity”.

Canadian researchers enrolled patients who were at least 66 years of age, taking a statin that is not significantly metabolised by CYP3A4 (e.g. rosuvastatin, pravastatin or fluvastatin) and either clarithromycin (n=51,523) or azithromycin (n=52,518). Clarithromycin inhibits CYP3A4 and the transporters OATP1B1 and OATP1B3, which move statins into hepatocytes. Azithromycin does not inhibit CYP3A4, OATP1B1 or OATP1B3.

Compared with people receiving statins not metabolised by CYP3A4 who were also taking azithromycin, patients co-prescribed clarithromycin were 65 per cent more likely to be admitted to hospital with acute kidney injury during the 30 days after the start of the co-prescription (adjusted relative risk [RR] 1.65). Concurrent clarithromycin also increased admissions with hyperkalaemia (RR 2.17) and all-cause mortality (RR 1.43) over the 30 days.

The increased risk of admission with rhabdomyolysis (RR 2.27) was not significant. The absolute increase in risk for each outcome was “probably” less than 1 per cent but, since these drugs are widely used, the findings could be important from a population perspective. (CMAJ DOI:10.1503/cmaj. 140950)