Azithromycin Use with GFR 46 mL/min
Yes, azithromycin can be prescribed at standard doses without adjustment for a patient with GFR 46 mL/min, as no dose modification is required for renal impairment unless GFR falls below 10 mL/min. 1
Dosing Recommendations
The FDA label explicitly states that no dosage adjustment is recommended for subjects with renal impairment (GFR ≤80 mL/min). 1 This is based on pharmacokinetic data showing that mean AUC0-120 was similar in subjects with GFR 10-80 mL/min compared to those with normal renal function. 1
Standard Dosing Applies
- For most common indications (community-acquired pneumonia, acute bacterial sinusitis, skin infections), the standard regimen is 500 mg on Day 1, followed by 250 mg once daily on Days 2-5. 1
- For acute bacterial exacerbations of COPD, either 500 mg daily for 3 days OR the 5-day regimen above can be used. 1
- Azithromycin can be taken with or without food. 1
Pharmacokinetic Rationale
Azithromycin undergoes minimal renal elimination, which explains why dose adjustment is unnecessary in moderate renal impairment. 2 A pharmacokinetic study demonstrated that neither the area under the plasma concentration curve, distribution volume (16 L/kg body weight), nor maximal plasma concentration were significantly affected by renal insufficiency. 2
- The nonrenal clearance remains unaffected by renal impairment. 2
- Only when GFR drops below 10 mL/min does the AUC increase by 35%, warranting caution but still not requiring mandatory dose reduction. 1
Important Safety Considerations
Caution in Severe Renal Impairment
Exercise caution only when GFR is below 10 mL/min, as drug exposure increases by 35% in this population. 1 Your patient with GFR 46 mL/min does not fall into this category.
Rare but Serious Adverse Effect
Be aware that azithromycin has been associated with acute interstitial nephritis (AIN), though this is rare. 3 One case report documented biopsy-proven AIN requiring hemodialysis after a standard 5-day course (1.5 g total dose). 3 The Naranjo scale indicated a definite relationship (score 10) between azithromycin and AIN in this case. 3
- Monitor for signs of AKI (nausea, vomiting, decreased urine output, rising creatinine) during and after treatment. 3
- If AKI develops, discontinue azithromycin immediately and consider renal biopsy if the diagnosis is unclear. 3
Clinical Context
This recommendation contrasts sharply with many other antibiotics that require dose adjustment at GFR thresholds of 30-50 mL/min. For comparison:
- Fluconazole requires 50% dose reduction when CrCl ≤50 mL/min. 4
- Ciprofloxacin requires dose adjustment when GFR falls below 30 mL/min. 5
- Levofloxacin requires dosing interval extension when CrCl <50 mL/min. 6
Azithromycin's lack of required dose adjustment in moderate renal impairment makes it a particularly convenient choice for patients with GFR in the 30-60 mL/min range. 1, 2