What is the dosage adjustment for oral (PO) azithromycin in a patient with impaired renal function, specifically a glomerular filtration rate (GFR) of 15?

Azithromycin Dosing in Severe Renal Impairment (GFR 15)

No dosage adjustment is required for oral azithromycin in patients with a GFR of 15 mL/min/1.73m². 1

Pharmacokinetic Rationale

Azithromycin's pharmacokinetic properties make it uniquely suitable for use in renal impairment:

• The FDA drug label clearly states: "No dosage adjustment is recommended for subjects with renal impairment (GFR ≤80 mL/min)" 1
• Azithromycin is primarily eliminated through biliary excretion and transintestinal secretion, with minimal renal clearance 2
• Only about 6% of an oral dose is excreted unchanged in urine 2
• Studies specifically examining azithromycin in renal impairment have confirmed that pharmacokinetic parameters remain largely unchanged:
  • Neither the area under the plasma concentration curve
  • Nor the distribution volume
  • Nor the maximal plasma concentration are significantly affected by renal insufficiency 3

Clinical Considerations

Standard Dosing Regimens

For patients with GFR of 15 mL/min/1.73m², use standard dosing:

• For respiratory infections: 500 mg on day 1, followed by 250 mg once daily on days 2-5
• For acute bacterial exacerbations of COPD: 500 mg daily for 3 days OR 500 mg on day 1, followed by 250 mg daily on days 2-5
• For genital infections: Single 1 gram dose 1

Important Monitoring Considerations

While no dose adjustment is needed, consider:

• Monitoring for potential adverse effects, particularly gastrointestinal symptoms (nausea, diarrhea, abdominal pain)
• Being aware that while the pharmacokinetics aren't significantly altered, the concentration of azithromycin in the tubular lumen ("tubular load") may be increased in renal impairment 3

Comparison with Other Antimicrobials

Unlike many other antimicrobials that require significant dosage adjustments in renal impairment, azithromycin stands out:

• The KDOQI guidelines specifically note that macrolides require dose reduction by 50% when GFR < 30 mL/min/1.73m² 4, but this is a general statement about macrolides as a class
• The FDA label for azithromycin specifically states no dose adjustment is needed 1
• This contrasts with other antimicrobials like fluoroquinolones (reduce dose by 50% when GFR < 15 mL/min/1.73m²) and aminoglycosides (require significant dose adjustments) 4

Clinical Evidence

Research studies support the safety of standard azithromycin dosing in renal impairment:

• A pharmacokinetic study concluded: "the dosage regimen of azithromycin in renal impairment may (and should) be the same as in patients with normal renal function" 3
• The mean AUC0-120 was similar in subjects with GFR 10-80 mL/min compared to subjects with normal renal function 1

Conclusion

Azithromycin can be administered at standard doses in patients with GFR of 15 mL/min/1.73m², with no adjustment needed due to its primarily non-renal elimination pathway.