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Assessment of the risk of hypotension with the combined use of macrolides and calcium channel blockers

It is known that clarithromycin and the erythromycin macrolides have the capacity to potentiate the action of antihypertensives from the group of calcium channel blockers by inhibiting the isoenzyme 3A4 of cytochrome P450. However, this drug interaction is not receiving good attention and its consequences for the moment are not sufficiently characterized. Therefore, the relevance of conducting a study to determine the risk of developing hypotension or shock with the need for additional hospital treatment while prescribing calcium channel blockers and macrolides is understandable.

A population-based group crossover study was conducted from April 1, 1994 to March 31, 2009, in which patients 66 years of age and older who received drugs from the calcium channel blocker group became participants. The study involved patients who needed treatment for hypotension or clinically significant shock in a hospital setting. For each antibiotic in the macrolide group (erythromycin, clarithromycin or azithromycin, indicating the duration of treatment), the researchers determined the risk of hypotension or shock when used with a calcium channel blocker.

Of the 7,100 patients hospitalized for hypotension due to calcium channel blockers, 176 also received macrolides. In patients taking erythromycin (the most pronounced inhibitor of cytochrome P450 3A4), the development of hypotension was most often observed (odds ratio 5.8, 95% CI 2.3-15.0 ). More rarely, hypotension has been reported in patients taking clarithromycin (odds ratio 3.7, 95% confidence interval 2.3-6.1). Acceptance of azithromycin, which does not have the ability to inhibit cytochrome P450 3A4, when combined with a calcium channel blocker, was not accompanied by an increased risk of hypotension (odds ratio 1.5, 95% confidence interval 0.8-2.8). Similar results were obtained in the stratified analysis of patients taking only drugs of the calcium channel blockers of dihydropyridines.

Thus, in patients of an older age group, the combined use of calcium channel blockers with erythromycin or clarithromycin resulted in an increased risk of hypotension or shock with the need for a additional hospital treatment. Therefore, if a patient who is constantly taking calcium channel blockers is to be prescribed macrolide, azithromycin should be preferred.