Antibiotic interactions: Answers to 4 common questions
Which antibiotics should you consider when a patient is taking warfarin? Which ones are associated with drug-induced, prolonged QT intervals? Read on.
3. Which drugs prolong QT intervals?
Macrolides and fluoroquinolones are 2 classes of antibiotics associated with prolonged QT intervals, but other drugs and risk factors are important to consider, as well.
Physicians often receive phone calls from pharmacists warning about drug-drug interactions when they prescribe macrolides or fluoroquinolones for patients already taking medications known to prolong QT intervals or inhibit cytochrome P450 enzymes. Long QT syndrome increases the risk of TdP, a life-threatening arrhythmia. While TdP is rare, its severity warrants a discussion of risk factors and the likelihood of occurrence.
Two QT interval prolonging medications used together in healthy individuals does not warrant a change in therapy. TdP is most likely to occur when 2 or more QT interval prolonging medications are used in a patient who is already at high risk for arrhythmia because of risk factors such as prolonged QT interval at baseline, family history of prolonged QT intervals, female gender, age >60 years, electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia), underlying comorbid diseases (eg, chronic heart failure, left ventricular hypertrophy, atrial fibrillation), hypertension, bradycardia, and genetic (ion channel) polymorphisms.26,27
Antiarrhythmics and antipsychotics are most commonly associated with drug-induced prolonged QT interval, with most case reports and research being linked to antiarrhythmics (TABLE 42).28 But macrolide and fluoroquinolone antibiotics also have been associated with TdP, although to a lesser extent. In a retrospective analysis of case reports of TdP involving macrolides, erythromycin was present (with or without other medications thought to prolong QT) in 53% of the cases and clarithromycin was involved in 36% of the reports.29
An analysis of 2 studies by the US Food and Drug Administration estimated an occurrence rate of serious cardiac arrhythmias of 46 to 85 per 100,000 users with cardiovascular disease, compared to 5 to 44 per 100,000 users without cardiovascular disease.30 And this may underestimate the actual incidence because spontaneous reporting of adverse effects declines the longer a drug is on the market. Ciprofloxacin is associated with less risk than levofloxacin and gatifloxacin (the latter of which is no longer available in the United States).26
A recent population-based study using data on over 10.6 million people from the Taiwan National Health Insurance Database examined the risk of cardiovascular death among patients using new-generation macrolides, fluoroquinolones, and β-lactam/β-lactamase inhibitors.31 The absolute risk of cardiovascular death per 1000 individuals was 0.06 for clarithromycin, 0.12 for ciprofloxacin, 0.13 for amoxicillin-clavulanate, 0.36 for azithromycin, 0.39 for levofloxacin, and 0.46 for moxifloxacin. The mean interval between first antibiotic use and the adverse cardiac event was <4 days. Not surprisingly, the highest risk was seen in patients with underlying cardiovascular disease.
Another population-based study, this time conducted in Hong Kong, evaluated the cardiovascular safety of clarithromycin compared to that of amoxicillin. Clarithromycin was found to increase the incidence of myocardial infarction, arrhythmia, and cardiac mortality in the short term, with the risk returning to baseline after treatment concluded.32 A binational cohort study of Danish and Swedish adults confirmed that fluoroquinolones (especially ciprofloxacin) do not increase the risk of a serious arrhythmia compared to penicillins.33
THE BOTTOM LINE For patients taking other QT interval prolonging medications or who are at a higher risk for TdP, consider using clarithromycin over erythromycin or azithromycin for a macrolide antibiotic or ciprofloxacin over levofloxacin or moxifloxacin if a fluoroquinolone is warranted. Using 2 drugs that may increase the QT interval is likely safe in the absence of certain risk factors.
