Azithromycin Dosing in Chronic Kidney Disease
No dose adjustment of azithromycin is required for patients with chronic kidney disease, regardless of the severity of renal impairment. 1
Evidence-Based Dosing Recommendations
Standard Dosing Applies Across All CKD Stages
The FDA label explicitly states that no dosage adjustment is recommended for subjects with renal impairment (GFR ≤80 mL/min), as the mean AUC0-120 was similar in subjects with GFR 10 to 80 mL/min compared to subjects with normal renal function 1
Even in severe renal impairment (GFR <10 mL/min), the AUC increased only 35% and Cmax increased 61% compared to normal renal function, which the FDA considers manageable without dose adjustment 1
Caution should be exercised when azithromycin is administered to subjects with severe renal impairment (GFR <10 mL/min), but formal dose reduction is not required 1
Pharmacokinetic Rationale
Azithromycin undergoes primarily biliary excretion as unchanged drug, making it a major route of elimination rather than renal excretion 1
Only approximately 6% of the administered dose appears as unchanged drug in urine over the course of a week, explaining why renal impairment has minimal impact on drug clearance 1
The nonrenal clearance of azithromycin is not affected by renal insufficiency, and neither the area under the plasma concentration curve nor the distribution volume in steady state (16 L/kg body weight) are significantly affected by renal impairment 2
Clinical Study Support
A pharmacokinetic study in 42 adults with varying degrees of renal impairment demonstrated that following a single 1,000 mg oral dose, mean Cmax and AUC0-120 increased by only 5.1% and 4.2% respectively in subjects with mild to moderate renal impairment (GFR 10 to 80 mL/min) 1
Research specifically examining azithromycin in renal insufficiency concluded that the dosage regimen in renal impairment may (and should) be the same as in patients with normal renal function 2
Hemodialysis Considerations
For patients on hemodialysis, no specific timing of administration relative to dialysis sessions is required, as azithromycin is not significantly removed by dialysis 1
This contrasts with many other antibiotics that require post-dialysis dosing 3, 4
Common Pitfalls to Avoid
Do not reduce azithromycin doses based on creatinine clearance calculations, as this is unnecessary and may lead to subtherapeutic levels and treatment failure 1, 2
Avoid confusing azithromycin with other macrolides or antibiotics that do require renal dose adjustment 5
Do not assume all antibiotics need dose adjustment in CKD—azithromycin is a notable exception due to its predominantly hepatobiliary elimination 1, 2
Monitoring Recommendations
While dose adjustment is not required, monitor patients with severe renal impairment (GFR <10 mL/min) more closely for potential adverse effects given the modest increase in drug exposure 1
Standard monitoring for azithromycin adverse effects (QT prolongation, hepatotoxicity, gastrointestinal symptoms) applies regardless of renal function 1