January 7, 2015
Mixing Clarithyromycin, Even With 'Safer' Statins, Can Create Adverse Events

London, Ontario—Pharmacists might want to check to see if older patients prescribed the antibiotic clarithromycin are also taking statins.

Combining statins with the antibiotic increases the risk of adverse events, which may require hospital admission for older people, according to a new study published in the Canadian Medical Association Journal.

The challenge, according to background in the article, is that statins are so widely prescribed, with projections estimated at more than 1 billion patients around the globe. Although uncommon, according to the study from Western University in London, Ontario, severe adverse events can occur in some patients when certain medications affect the way statins are metabolized.

While conventional wisdom is that some types of statins, i.e., rosuvastatin and pravastatin, are metabolized differently than others in the group, new biological studies suggest this may not be the case.

To investigate the issue further, the researchers compared the use of two common antibiotics, clarithromycin and azithromycin, in older adults who were also taking rosuvastatin, pravastatin or fluvastatin to determine if adverse events occurred. The study focused on data from the Institute for Clinical Evaluative Sciences on 104,041 statin users aged 66 or over in Ontario, who also had a prescription for one of the antibiotics—51,523 for clarithromycin and 52,518 for azithromycin.

Results indicate that coprescription of clarithromycin and a statin was associated with a modest increase in the number of deaths and hospital admissions for acute kidney injury or high potassium levels.

Compared with the control group, patients coprescribed clarithromycin and those statins were at increased 30-day risk of hospital admission with acute kidney injury (adjusted relative risk 1.65), admission with hyperkalemia (adjusted RR 2.17), and all-cause mortality (adjusted RR 1.43), according to the study.

While adjusted RR for admission with rhabdomyolysis was 2.27, the absolute increase in risk for each outcome was small and likely below 1%, the authors point out.

The adverse events may reflect statin toxicity among older adults according to study authors.

“The population impact of this preventable drug-drug interaction can be considered in the context of the high frequency of clarithromycin and statin co-prescription (rosuvastatin, or Crestor, was the second most commonly dispensed drug in Canada in 2010),” writes lead author Amit Garg, MD, PhD, a nephrologist at Western and also a scientist at the Lawson Health Research Institute and Institute for Clinical Evaluative Sciences.

The study notes that previous studies have indicated that those statins could be safer than others to combine with clarithromycin.

“Our findings indicate that unintended adverse events may still occur, possibly because of [other metabolic pathways]. To prevent toxicity, the use of azithromycin or another antibiotic that does not interact with statins can be considered,” the authors conclude.

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