Clarithromycin-induced digoxin intoxication

OBJECTIVE: To report a case of clarithromycin-induced digoxin intoxication. CASE SUMMARY: A 78-year-old white man with ischemic cardiomyopathy and chronic renal insufficiency was admitted 4 days after being prescribed clarithromycin for a suspected episode of bronchitis. He reported weakness, asthenia, and gastrointestinal symptoms; the digoxin serum concentration was measured at 3.89 ng/mL. The patient recovered uneventfully after digoxin and clarithromycin were discontinued. DISCUSSION: Erythromycin frequently interacts with other drugs that are also metabolized by the CYP3A4 isoenzyme. However, erythromycin is hypothesized to interact with digoxin by inhibiting Eubacterium lentum, which is a normal inhabitant of the human gut and is responsible for intestinal metabolism of digoxin in 10% of patients. Since clarithromycin shares a comparable antibacterial spectrum with erythromycin, the possibility of a drug interaction with digoxin remains. Only four cases of clarithromycin interacting with digoxin have been reported to date. Clinically, this interaction may have been more obvious because of our patient's moderate renal dysfunction and serum digoxin concentrations in the upper therapeutic range prior to clarithromycin initiation. Other causes for digoxin intoxication could not be identified. CONCLUSIONS: Clarithromycin may inhibit the growth of E. lentum, which can lead to an increase in digoxin bioavailability and blood concentrations in patients in whom this intestinal metabolic pathway is present. Patients at risk include those with renal dysfunction, with serum concentrations in the upper therapeutic range, or with measured digoxin concentrations that are much lower than predicted by pharmacokinetic calculations. For these patients, appropriate therapy includes the selection of an alternative, noninteracting antibiotic or, if this is not possible, a temporary reduction of digoxin dosage.