Azithromycin Dosing in ESRD
No dose adjustment is required for azithromycin (Z-pack) in patients with end-stage renal disease, including those on hemodialysis or peritoneal dialysis. 1
Standard Dosing Applies
- Use the standard adult dosing regimen without modification: 500 mg on Day 1, followed by 250 mg once daily on Days 2-5 (total 1.5 g over 5 days) 1
- Alternative 3-day regimen of 500 mg daily for 3 days is also acceptable without adjustment 1
- The FDA label explicitly states "no dosage adjustment is recommended for subjects with renal impairment (GFR ≤80 mL/min)" 1
Pharmacokinetic Rationale
- Azithromycin's unique elimination profile makes it safe in ESRD: Only 6% of the drug is excreted unchanged in urine, with biliary excretion being the major route of elimination 1
- In patients with severe renal impairment (GFR <10 mL/min), AUC increases by only 35% and Cmax by 61% compared to normal renal function—a modest increase that does not warrant dose reduction 1
- The nonrenal clearance of azithromycin remains unaffected by renal insufficiency 2
- The large volume of distribution (31.1 L/kg) and extensive tissue penetration buffer against accumulation 1
Key Distinctions from Other Macrolides
- Unlike clarithromycin, which requires 50% dose reduction when CrCl <30 mL/min 3, azithromycin maintains standard dosing 4
- This distinction is critical—do not extrapolate clarithromycin dosing adjustments to azithromycin 4
Important Caveats
- Exercise caution in severe renal impairment (GFR <10 mL/min) despite no formal dose adjustment being required, as the FDA label notes increased drug exposure 1
- Monitor for potential adverse effects, though the safety profile remains favorable 2
- Preserve peripheral veins in patients with stage III-V CKD who may progress to hemodialysis 5
- Be aware that azithromycin can rarely cause acute interstitial nephritis, which may worsen renal function 6