Azithromycin Dosing in Renal Impairment
No dose adjustment of azithromycin is required in patients with renal impairment, including those with severe renal dysfunction (GFR ≤10 mL/min). 1
FDA-Approved Dosing Guidance
The FDA label explicitly states that no dosage adjustment is recommended for patients with renal impairment (GFR ≤80 mL/min), though caution should be exercised in severe renal impairment (GFR <10 mL/min) due to a 35% increase in AUC compared to normal renal function 1. This recommendation is based on pharmacokinetic data showing similar drug exposure across the spectrum of renal function, with only modest accumulation in end-stage renal disease 1.
Pharmacokinetic Rationale
- Azithromycin is primarily eliminated through nonrenal pathways, with only 11-16% excreted unchanged in urine 2, 3
- The area under the curve (AUC), distribution volume (approximately 16 L/kg), and maximum plasma concentration remain unchanged across all degrees of renal insufficiency 3
- Nonrenal clearance mechanisms are not affected by renal dysfunction 3
- Even in patients with GFR <10 mL/min, the 35% increase in AUC does not warrant routine dose reduction, though monitoring is prudent 1
Contrast with Other Antibiotics
Unlike aminoglycosides (streptomycin, amikacin, kanamycin) and other renally-cleared antibiotics that require substantial dose adjustments or interval changes in renal impairment 4, azithromycin's predominantly hepatic elimination pathway makes it uniquely suitable for use without modification in renal disease 3.
Clinical Caveats
- Hemodialysis does not significantly remove azithromycin, so no supplemental dosing is needed post-dialysis 3
- While rare, azithromycin can cause acute interstitial nephritis, which presents as acute kidney injury with fever, rash, and eosinophilia—this is a hypersensitivity reaction unrelated to baseline renal function 5
- The standard dosing regimen (500 mg day 1, then 250 mg daily for days 2-5, or alternative regimens) remains appropriate regardless of creatinine clearance 1