Azithromycin + Digoxin = Precautionary

Effect on Concentration

Azithromycin
Unknown
Applies within class?
No
Digoxin
Increase
Applies within class?
No

Pharmacologic Effects

Azithromycin
Effect
N/A
Applies within class?
No
Digoxin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-May-2020

Summary

Azithromycin was the second most potent inhibitor of P-glycoprotein mediated digoxin transport of all the macrolides tested.

Sources

Role of P-Glycoprotein Inhibition for Drug Interactions: Evidence From in Vitro and Pharmacoepidemiological Studies ^

Study Design

In vitro, the effect of macrolides on polarised P-glycoprotein-mediated digoxin transport was investigated in Caco-2 cells. In a pharmacoepidemiological study, we analysed the serum digoxin and digitoxin concentrations with and without coadministration of P-glycoprotein inhibitors in hospitalised patients.

Study Results

All macrolides inhibited P-glycoprotein-mediated digoxin transport, with concentrations producing 50 inhibition (IC(50)) values of 1.8, 4.1, 15.4, 21.8 and 22.7 micromol/L for telithromycin, clarithromycin, roxithromycin, azithromycin and erythromycin, respectively. Coadministration of P-glycoprotein inhibitors was associated with increased serum concentrations of digoxin (1.3 /- 0.6 vs 0.9 /- 0.5 ng/mL, p 0.01). Moreover, patients receiving macrolides had higher serum concentrations of cardiac glycosides (p 0.05).

Study Conclusions

Macrolides are potent inhibitors of P-glycoprotein. Drug interactions between P-glycoprotein inhibitors and substrates are likely to occur during hospitalisation.

References

Eberl S. Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies. Clin Pharmacokinet. 2007; 12: 1039-49.