Azithromycin Dosing in End-Stage Renal Disease (ESRD)
No dosage adjustment of azithromycin is required for patients with end-stage renal disease (ESRD). 1
Pharmacokinetic Rationale
- Azithromycin is primarily eliminated through biliary excretion as unchanged drug, with only approximately 6% of the administered dose appearing as unchanged drug in urine 1
- The pharmacokinetics of azithromycin are not significantly altered in patients with mild to moderate renal impairment (GFR 10-80 mL/min) compared to those with normal renal function 1, 2
- In patients with severe renal impairment (GFR <10 mL/min), the mean AUC0-120 increases by only 35% compared to subjects with normal renal function 1
- Studies specifically examining azithromycin in renal impairment have shown that neither the area under the plasma concentration curve nor the distribution volume in steady state are significantly affected by renal insufficiency 3
Recommended Dosing in ESRD
- Standard adult dosing should be used in ESRD patients 1:
- For respiratory infections: 500 mg on day 1, followed by 250 mg once daily on days 2-5 1
- 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 1
- For genital infections: Single 1-gram dose 1
- For gonococcal infections: Single 2-gram dose 1
Peritoneal Dialysis Considerations
- Azithromycin is not substantially removed by continuous ambulatory peritoneal dialysis (CAPD) 4
- Peritoneal dialysis clearance is minimal at approximately 0.06 L/hr 4
- The elimination half-life in ESRD patients on CAPD is approximately 84.55 hours, compared to >40 hours in healthy volunteers 4
Clinical Considerations
- While the FDA label states that "caution should be exercised when azithromycin is administered to subjects with severe renal impairment," no specific dose adjustment is recommended 1
- Unlike other macrolides such as clarithromycin (which requires a 50% dose reduction when CrCl <30 mL/min), azithromycin maintains its standard dosing in ESRD 5
- The nonrenal clearance of azithromycin is not significantly affected by renal insufficiency, unlike some other drugs that may have reduced hepatic clearance in ESRD 3, 6
Monitoring Recommendations
- Monitor for potential side effects, particularly gastrointestinal symptoms (nausea, diarrhea, abdominal pain) which are the most common adverse reactions 7
- No specific additional monitoring of drug levels is required in ESRD patients 1, 3
Important Considerations
- Food can significantly decrease azithromycin bioavailability by approximately 50%; however, this interaction is not specific to ESRD patients 7
- The extensive tissue distribution and intracellular accumulation of azithromycin (volume of distribution 23-35 L/kg) contribute to its unique pharmacokinetic profile that remains largely unchanged in ESRD 2, 7