Researchers found that patients on calcium channel blockers who were given the antibiotics erythromycin (brands like E-Mycin) or clarithromycin (Biaxin) were at increased risk of being hospitalized for dangerously low blood pressure.
A third antibiotic in the same class — azithromycin (Zithromax) — was not linked to the risk. And the researchers say it should be chosen over the other two antibiotics for people on calcium channel blockers.
The three bacteria-killing drugs are what are known as macrolide antibiotics — the most widely prescribed class of antibiotics worldwide. In the U.S. alone, more than 66 million prescriptions were filled in 2008.
For their part, calcium channel blockers are among the most commonly used long-term medications. They include drugs like amlodipine (Norvasc), felodipine (Plendil), nifedipine (Procardia, Adalat) and diltiazem (Cardizem, Dilacor, Tiazac).
“It’s not far-fetched that a person would be on a calcium channel blocker and macrolide at the same time,” said Dr. David M. Juurlink, the senior researcher on the new study, which appears in the Canadian Medical Association Journal.
The problem with erythromycin and clarithromycin is that they inhibit an enzyme vital to metabolizing calcium channel blockers, explained Juurlink, of the Institute for Clinical Evaluative Sciences in Toronto.
As a result, blood levels of the calcium channel blocker spike, leading to sometimes severe drops in blood pressure.
Azithromycin, in contrast, does not block that same enzyme.
Researchers have known about these drug actions, but until now there had been no large study looking at the risk of severe low blood pressure among patients on calcium channel blockers and macrolides.
For their study, Juurlink and his colleagues looked at medical records for more than 999,000 Ontario residents age 66 and up who were on a calcium channel blocker at some point between 1994 and 2009.
During that time, 7,100 were hospitalized for severe drops in blood pressure. Of those patients, 131 had been on a macrolide antibiotic in the week before their hospitalization.
Juurlink’s team found that erythromycin treatment was linked to a six-fold increase in the risk of hospitalization for low blood pressure. Clarithromycin was tied to a nearly four-fold increase.
Because of the study design, Juurlink said he could not give a precise figure for the absolute risk of severe hypotension from the drug combination. But he said it was “probably very low” for any particular person.
Still, Juurlink added, it appears to be an avoidable risk.
“Doctors should be aware of the risk, and know that there is an alternative out there,” he said. “If you have to prescribe a macrolide antibiotic to someone on a calcium channel blocker, it makes sense to give azithromycin.”
As for other classes of blood pressure drugs — like ACE inhibitors and beta-blockers — they do not seem to be susceptible to the effects of the two antibiotics, according to Juurlink.
The current study focused on older adults because they are most vulnerable to the consequences of drops in blood pressure. They could, for instance, get dizzy enough to fall and break a hip. Or in severe cases, low blood pressure can deprive the organs of blood and oxygen, leading to shock and potentially fatal organ damage.
“Younger patients are better able to tolerate a drop in blood pressure,” Juurlink said.
However, he added, azithromycin would still be the wise choice for younger people on calcium channel blockers as well.
Juurlink also pointed out that erythromycin and clarithromycin can boost blood levels of cholesterol-lowering statins. In that case, he said, the concern would be increasing the risk of serious muscle damage, a known side effect of statins.
So it would be wise for people on statins to take azithromycin over the other two macrolides, Juurlink said.
One of Juurlink’s co-researchers on the study has served as a consultant to Zithromax maker Pfizer Inc. All three macrolide antibiotics are also available as generics.