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Doctors need to be careful when prescribing macrolide antibiotics to patients on calcium-channel blockers (CCBs) because of an underappreciated drug-drug interaction that can lead to hypotension and shock, new research shows [1]. The findings are important because millions of people take CCBs and many are prescribed antibiotics every year, say Dr Alissa J Wright (University of Toronto, ON) and colleagues in a study published online January 17, 2011 in CMAJ.Although the interaction "is perfectly predictable based upon the pharmacology of the drugs, it has been previously documented in only about five case reports," senior author Dr David Juurlink(University of Toronto, ON) explained to heartwire . He says that this study is the first rigorous attempt to describe the clinical consequences of this interaction: "In a sense, this paper attaches a risk estimate to how dangerous this drug combination is."
The research also shows that there is a safe choice if doctors do need to use a macrolidelike antibiotic, he adds. The study found that macrolides such as erythromycin orclarithromycin increase the risk of hypotension if used in combination with a CCB, but a related antibiotic, azithromycin, does not.
Juurlink observes that "it's not wrong to use a macrolide [in a patient taking a CCB], but it's probably more sensible if you are going to use one to use azithromycin. If, for some reason, you had to use clarithromycin or erythromycin, it might be reasonable just to edge back a little bit on the dose of the CCB."
Biggest Risk With Erythromycin
In their population-based, nested, case-crossover study, Wright and colleagues analyzed the healthcare records of around a million individuals over the age of 65 who were receiving a single CCB between 1994 and 2009. Of these patients, 7100 were admitted to hospital for hypotension or shock, and 176 had received a macrolide antibiotic (36 received erythromycin, 100 received clarithromycin, and 40 received azithromycin) in a seven-day interval immediately before admission to the hospital or in a seven-day control interval one month earlier. For each antibiotic, the researchers estimated the risk of hypotension or shock associated with the use of a CCB.
They found a strong association between erythromycin use and hospital admission for hypotension, with an almost sixfold increased risk of low BP (odds ratio 5.8), and a lower but still significant risk associated with the use of clarithromycin (OR 3.7). In contrast, there was no such link with azithromycin use (OR 1.5).
Juurlink explains that, pharmacologically, macrolide antibiotics inhibit a cytochrome P450 enzyme, which metabolizes all CCBs, so their use can lead to the accumulation of the CCB and potential toxicity. But azithromycin does not inhibit this cytochrome P450 enzyme. The use of combination CCBs and macrolide antibiotics "isn't exactly uncommon, but no one has actually ever attached a measure of how dangerous the combination is, and that's what this study does," he notes.
The findings, says Juurlink, apply to all CCBs, because they are all metabolized by the same pathway, although it may be a bigger problem with some than others, he says, adding that his team could not examine the risks for separate CCBs because of a lack of statistical power.
Nevertheless, the results "have considerable clinical relevance, highlighting the consequences of an underappreciated yet avoidable drug interaction involving medications used by millions of people every year. Clinicians should be aware of the potential interaction between these drugs," he and his colleagues state.
Juurlink adds that although the use of erythromycin is declining, clarithromycin is still used frequently. "But I don't think clarithromycin and azithromycin are that different in price, quite frankly, so the latter represents a good choice if macrolide antibiotic therapy is required."


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