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Potentially fatal interaction between azithromycin and disopyramide
E V Granowitz1, K J Tabor, J B Kirchhoffer
1Department of Medicine, Baystate Medical Center, Springfield, Massachusetts 01199, USA. eric.granowitz@bhs.org
Abstract:
A patient on disopyramide developed disopyramide toxicity when treated concurrently with azithromycin. Evidence of toxicity included an elevated serum disopyramide level and ventricular tachycardia requiring cardioversion. The azalide antibiotic presumably inhibited dealkylation of disopyramide to its major metabolite, mono-N-dealkyldisopyramide. Physicians should avoid using azithromycin in patients on disopyramide. If this drug combination is unavoidable, disopyramide levels must be closely monitored.
Insights
Concurrent use of azithromycin with disopyramide can lead to dangerous disopyramide toxicity. This drug interaction, evidenced by elevated disopyramide levels and ventricular tachycardia, necessitates careful monitoring or avoidance of azithromycin in patients on disopyramide.
Area of Science:
- Clinical Pharmacology
- Drug Interactions
- Cardiology
Background:
- Disopyramide is an antiarrhythmic medication used to treat irregular heart rhythms.
- Azithromycin is a commonly prescribed macrolide antibiotic.
- Drug metabolism pathways can be significantly altered by concurrent medication use.
Observation:
- A case study identified a patient experiencing disopyramide toxicity during co-administration with azithromycin.
- Clinical manifestations included elevated serum disopyramide concentrations and hemodynamically unstable ventricular tachycardia requiring cardioversion.
Findings:
- Azithromycin, an azalide antibiotic, is presumed to inhibit the hepatic dealkylation of disopyramide.
- This inhibition leads to reduced metabolism of disopyramide to its primary metabolite, mono-N-dealkyldisopyramide.
- The accumulation of active disopyramide likely precipitated the observed toxicity.
Implications:
- Clinicians should exercise caution and consider avoiding the concurrent prescription of azithromycin in patients treated with disopyramide.
- If the combination is clinically necessary, therapeutic drug monitoring of serum disopyramide levels is crucial.
- This case highlights the importance of understanding drug-drug interactions affecting drug metabolism and patient safety.