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.

Digoxin Toxicity Secondary to Clarithromycin Therapy

OBJECTIVE: To report a case of digoxin toxicity thought to be secondary to clarithromycin therapy. CASE SUMMARY: A 78-year-old white woman with congestive heart failure taking digoxin 0.25 mg po qd presented to our hospital with nausea, vomiting, and diarrhea. She had taken clarithromycin 500 mg po bid for 3 days, and a serum digoxin concentration obtained the day of admission was 4.4 μg/L. An electrocardiogram (ECG) done on admission revealed ST segment changes consistent with digoxin effect and later asymptomatic, nonsustained ventricular tachycardia (NSVT). Clarithromycin was discontinued and digoxin was withheld at admission, resulting in the resolution of symptoms, ECG abnormalities, and NSVT on day 3 of hospitalization. On day 5 her serum digoxin concentration was 1.5 μg/L and digoxin therapy was reinstituted at a dose of 0.125 mg/d po. DISCUSSION: This is the fourth published case implicating clarithromycin as the cause of digoxin toxicity. This interaction is most likely due to clarithromycin eradication of digoxinmetabolizing gut flora, thereby increasing digoxin bioavailability. CONCLUSIONS: Approximately 10% of patients are thought to be extensive presystemic metabolizers of digoxin and may therefore be most susceptible to a drug interaction with clarithromycin. Serum digoxin concentrations in such patients should be monitored closely during clarithromycin therapy.