The US health agency, the FDA, has issued a warning to prescribing physicians about a common antibiotic, clarithromycin, due to an increased risk of cardiovascular events and death in people with coronary artery disease.
According to FDA, physicians should be careful, even consider antibiotic alternatives to clarithromycin, in all patients with coronary artery disease.
This decision comes in the aftermath of the CLARICOR study which showed an increase in these cardiovascular accidents occurring in coronary patients, after usual treatment for 2 weeks with clarithromycin (in the following year).
A review of the data concerning this antibiotic in patients included in CLARICOR was then carried out. over 10 years.
An objectified risk
A large clinical trial, called CLARICOR, had shown an unexpected increase in the number of deaths after one year or more of follow-up in patients with coronary artery disease who had received a two-week treatment with clarithromycin.
Some observational studies then found an increase in death or other serious heart problems, while others did not: of the 6 observational studies published to date in patients with or without coronary artery disease, two have found a long-term risk. clarithromycin, and four did not demonstrate this risk.
A controlled and demonstrative study
Overall, the results of the CLARICOR study, which is prospective, placebo-controlled, represent the strongest evidence in favor of the increased risk compared to the results of observational studies. There are no prospective, randomized, controlled trials with adequate long-term safety measures after treatment with clarithromycin in patients without heart disease.
Within the European Union, the additional risk of heart problems has been assessed by the EMA as part of a regular assessment of the benefit / risk balance of clarithromycin. This assessment took into account a number of recently published studies including the CLARICOR study.
No explanation for this increased risk
There is no clear explanation on the mechanism by which clarithromycin would cause more deaths and cardiovascular events than placebo.
Clarithromycin is a macrolide antibiotic commonly prescribed for ENT, skin and respiratory infections for over 25 years. It is also an antibiotic of particular interest in certain rare opportunistic infections such as infections with Mycobacterium Avium.
The cardiovascular risks associated with macrolides including clarithromycin, and in particular the risks of rare but serious heart rhythm disturbances, are known (QT prolongation) and this is why the European information in the summaries of product characteristics recommends caution in patients at increased risk of developing these disorders.
According to the FDA, however, this effect would not be at the origin of the disorders and deaths observed, these) having been observed only in coronary patients.
Reassessment in December by Europe
An evaluation of clarithromycin was carried out in December 2017 by the European Medicines Agency (EMA). This concluded that “although the evidence for a long-term risk of cardiovascular disorders with clarithromycin or a mechanism that may lead to it is limited, there is sufficient evidence of a low risk of heart attack and of short-term deaths “.
The EMA therefore recommended updates to the information in the summaries of product characteristics for all medicines containing clarithromycin to include more information on short-term risk. It was also emphasized that the benefit continues to outweigh the risks and that clarithromycin remains a vital treatment option.
The position of the French Medicines Safety Agency (ANSM) aligns with that of the EMA.
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