Mixing clarithromycin with statins could lead to hospitalization

The antibiotic clarithromycin and cholesterol-lowering statins are some of the most widely prescribed drugs in the world. New research, however, has found that certain combinations of the two could increase the risk of adverse events and, in certain cases, could lead to hospitalization.

The common antibiotic clarithromycin is frequently prescribed alongside statins.

The study, published in the Canadian Medical Association Journal (CMAJ), announces its findings following a comparison of the use of two common antibiotics in adults who were also using statins.

According to the researchers, statins may soon be recommended for over 1 billion people across the globe. They are a class of medicines frequently prescribed to lower cholesterol levels in the blood and to help reduce the risk of angina, heart attacks and stroke.

Previous studies have found that the way in which statins are metabolized by the body can be affected by the use of other medication, potentially leading to adverse events such as hospitalization and, in some extreme cases, death.

Many statins are metabolized by the enzyme CYP3A4, and the US Food and Drug Administration (FDA) warn against the use of drugs that inhibit this enzyme alongside statins that are metabolized by CYP3A4.

Certain types of statins such as rosuvastatin and pravastatin are metabolized differently by the body, however. Most health experts have held that the metabolism of these particular statins is unaffected by some medications, though new evidence has begun to suggest this theory might be incorrect.

Clarithromycin is an antibiotic that is prescribed to treat various bacterial infections of the skin and respiratory system, as well as stomach ulcers in combination with other medicines. As well as inhibiting CYP3A4, it is believed that clarithromycin could inhibit certain amino acids potentially involved in the metabolism of statins such as rosuvastatin and pravastatin.

The researchers set out to examine the effects of clarithromycin on patients using rosuvastatin, pravastatin and fluvastatin - three statins that are not metabolized by CYP3A4.

'High frequency of clarithromycin and statin co-prescription'

For the population-based cohort study, the team analyzed data from the Institute of Clinical Evaluative Sciences. A total of 104,041 statin users aged 66 or older from Ontario, Canada, were assessed. Each participant also had a prescription for either clarithromycin (51,523) or the antibiotic azithromycin (52,518) - an antibiotic that does not inhibit the amino acids that clarithromycin does.

They found that the co-prescription of clarithromycin and a statin was linked to an increased rate of mortality and hospital admissions for acute kidney injury or high levels of potassium (hyperkalemia). According to the authors of the study, these adverse events could represent statin toxicity.

The CYP3A4-inhibiting qualities of clarithromycin cannot explain the increased risk of statin toxicity observed in the study, as only statins that were not metabolized by this enzyme were assessed, the authors write.

Previous studies had indicated that these statins are safer than others to take with clarithromycin, but the authors state that health risks remain present. In particular, the authors draw attention to how often these drugs are taken together:

"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)."

As the study was purely an observational one, its findings are limited by the possibility of unmeasured variables that may have impacted the results. In addition, the researchers cannot guarantee that the association between the adverse events and the combination of drugs is causal.

Despite these limitations, the authors urge caution. "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," they conclude.

References:

1.  Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4, Amit X. Garg, et al., CMAJ, doi:10.1503 /cmaj.140950, published online 22 December 2014, abstract.
2.  CMAJ news release, accessed 22 December 2014.
3.  Additional source: Drugs.com Clarithromycin, accessed 22 December 2014.