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The Precautionary and Prohibited Medications Database

Maintained by a collaboration of the University at Buffalo Pharmacology Specialty Laboratory and Frontier Science & Technology Research Foundation

 
Medications Azithromycin and Sildenafil
Designation Unknown or no reaction
Last updated 22-May-2020
Interaction History
Effect on concentration Azithromycin: Unknown

Sildenafil: No change
Pharmacologic effect Azithromycin: N/A

Sildenafil: N/A
Pharmacologic effect applies to drugs in the same class Azithromycin:

Sildenafil:
Pharmacologic effect description Azithromycin:

Sildenafil:
Potential pharmacokinetic effect Azithromycin: N/A

Sildenafil: N/A
Potential pharmacokinetic effect applies to drugs in the same class Azithromycin:

Sildenafil:
Potential pharmacokinetic mechanism Azithromycin:

Sildenafil:

Summary

Azithromycin did not affect the pharmacokinetics of sildenafil or its metabolite.

Sources

The Effects of Steady-State Erythromycin and Azithromycin on the Pharmacokinetics of Sildenafil in Healthy Volunteers

Study Design
In the erythromycin interaction study, 26 male volunteers (18--45 years of age) received open-label sildenafil 100 mg on day 1. Half received blinded erythromycin (500 mg) twice daily on days 2--6, and the other half received placebo. On day 6, all subjects received a second 100-mg dose of sildenafil. In the azithromycin interaction study, 24 male volunteers (19--33 years of age) received open-label 100 mg sildenafil on day 1. Half then received blinded azithromycin (500 mg) once daily on days 2--4, and the other half received placebo. On day 4, all subjects received another 100-mg dose of sildenafil. In both studies, blood samples were collected on the first and last study day for the analysis of plasma concentrations of sildenafil and its primary metabolite, UK-103,320. 
Study Results
Repeated dosing with erythromycin caused statistically significant increases in the AUC and Cmax of sildenafil (2.8-fold and 2.6-fold, respectively) but had no effect on Tmax, kel or t1/2. A statistically significant 1.4-fold increase in the AUC of UK-103,320 was also observed, as well as a significant decrease in kel, resulting in an increase of about 1 h in t1/2. In contrast, repeated dosing with azithromycin caused no significant change in any pharmacokinetic parameter of either sildenafil or UK-103,320. Erythromycin, azithromycin and sildenafil were well tolerated; adverse events were mild and transient. No subject withdrew from either trial for any reason related to study drug. 
Study Conclusions
These results indicate that erythromycin modifies the pharmacokinetics of sildenafil by inhibiting its CYP3A4-mediated first-pass metabolism. Given these data, a lower starting dose of sildenafil (25 mg) may be considered for patients receiving erythromycin or other potent CYP3A4 inhibitors. Azithromycin did not affect the pharmacokinetics of sildenafil; therefore, no adjustment in dosage is necessary for patients receiving these drugs concomitantly. 
References
Muirhead GJ. The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers. Br J Clin Pharmacol. 2002; Suppl 1: 37S-43S.  

Study information updated: 22-May-2020