Digoxin with macrolides

Macrolides The interaction of digoxin with macrolide antibiotics in patients with digitalis toxicity has been investigated in two recent studies. The association between hospitalization for digoxin toxicity and recent exposure to individual macrolide antibiotics has been investigated in a 15-year, population-based, nested case-control study [4 ]. Clarithromycin was associated with the highest risk of digoxin toxicity (OR = 15 95% Cl = 7.9, 28), whereas erythromycin and azithromycin were associated with much lower risks. 

Macrolide antibiotics In a retrospective population-based nested case-control study from the National Health Insurance Research Database details of patients with heart failure newly treated with digoxin were retrieved from the database [b "]. Patients who were admitted to hospitals with a diagnosis of digoxin intoxication were identified and compared with matched controls. There were 154058 patients 595 were cases and 27020 matched controls were selected for comparison. Prescription of clarithromycin at 7, 14, and 30 days before the index date was associated with a increased rate of hospitalization for digoxin intoxication of three to five times. Clarithromycin in a prescribed daily dose (PDD)/defined daily dose (DDD) ratio >2 led to a 55-fold increase in risk. This study provides empirical evidence that interactions of digoxin with clarithromycin increases the risk of hospitalization for digoxin intoxication in patients with heart failure. 

Use of the macrolides increases serum levels of digoxin and increases the effects of anticoagulants. Use of antacids decreases the absorption of most macrolides. The macrolides should not be administered with clindamycin, lincomycin, or chloramphenicol a decrease in the therapeutic activity of the macrolides can occur. Concurrent administration of the macrolides with theophylline may increase serum theophylline levels. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

When azithromycin is used concomitantly with digoxin, serum digoxin concentrations need to be monitored (47). While data on the effects of azithromycin on the intestinal metabolism of digoxin have not been reported so far, it is likely that it will affect Eubacterium lentum, like other macrolides. 

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