Drug Interactions between Lanoxin and telithromycin

MONITOR: Coadministration with telithromycin may increase the plasma concentrations of digoxin. The proposed mechanism is telithromycin inhibition of P-glycoprotein efflux pump in the intestine and renal proximal tubules, resulting in increased absorption and decreased excretion of digoxin. In healthy volunteers, telithromycin increased the peak plasma concentration (Cmax), trough plasma concentration (Cmin) and area under the concentration-time curve (AUC) of digoxin by 73%, 21% and 37%, respectively. However, trough plasma levels of digoxin (when equilibrium between plasma and tissue concentrations has been achieved) ranged from 0.74 to 2.17 ng/mL, and there were no significant changes in electrocardiographic parameters and no signs of digoxin toxicity in the volunteers. During postmarketing use, the interaction was suspected in a 58-year-old woman who developed digoxin toxicity while she was taking a 5-day course of telithromycin for acute bronchitis. The patient complained of general malaise and had experienced three episodes of syncope secondary to possible tachyarrhythmia prior to presentation at the emergency department. A randomly obtained (more than 6 hours after the dose) plasma digoxin level was elevated at 3.14 ng/dL, which was a 55% increase from her baseline steady-state digoxin level three months before admission. Electrocardiography showed several nonspecific repolarization anomalies, and measured cardiac markers were slightly elevated. Other risk factors that may have contributed to the patient's digoxin toxicity include renal dysfunction and electrolyte abnormalities (hypomagnesemia and slight hypokalemia). However, the temporal relationship to telithromycin administration strongly suggests an interaction.

MANAGEMENT: Pharmacologic response and serum digoxin levels should be monitored more closely whenever telithromycin is added to or withdrawn from therapy, and the digoxin dosage adjusted as necessary. Patients should be advised to notify their physician if they experience signs and symptoms of digoxin toxicity such as irregular heartbeats, slow pulse, nausea, anorexia, or visual changes.