What is the recommended dosing for Unasyn (Ampicillin/Sulbactam) in patients with impaired renal function undergoing dialysis?

Dosing of Unasyn (Ampicillin/Sulbactam) in Dialysis Patients

For patients on hemodialysis, Unasyn (Ampicillin/Sulbactam) should be dosed at 1.5-3 g every 24 hours, with administration after dialysis on dialysis days.

Pharmacokinetics in Renal Impairment

Ampicillin and sulbactam are both primarily eliminated by the kidneys, with approximately 71% of ampicillin and 78% of sulbactam excreted renally in patients with normal renal function 1. In patients with end-stage renal disease:

• The half-life of both components increases significantly
• Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam during a 4-hour session 1
• The ratio of ampicillin to sulbactam remains constant regardless of renal function

Dosing Recommendations Based on Renal Function

According to the FDA drug label for Ampicillin/Sulbactam 2, dosing should be adjusted based on creatinine clearance:

• Normal renal function: 1.5-3 g every 6-8 hours
• CrCl 15-29 mL/min: 1.5-3 g every 12 hours
• CrCl 5-14 mL/min: 1.5-3 g every 24 hours

Specific Recommendations for Hemodialysis Patients

For patients on hemodialysis, the following approach is recommended:

1. Administer 1.5-3 g every 24 hours
2. On dialysis days, administer the dose after the dialysis session
3. This prevents premature removal of the drug during dialysis

Research by Loeffler et al. 3 in critically ill patients with acute kidney injury undergoing extended dialysis supports a twice-daily dosing schedule of 2 g/1 g ampicillin/sulbactam, with one dose given after dialysis, to avoid underdosing. However, the FDA label 2 and earlier pharmacokinetic studies 1 support the once-daily dosing for standard hemodialysis patients.

Considerations for Peritoneal Dialysis

Limited data exists for patients on peritoneal dialysis. Studies have shown that ampicillin can be absorbed across the peritoneum when administered in dialysate 4, 5. Until more specific data becomes available, it is reasonable to follow the dosing recommendations for patients with severe renal impairment (CrCl 5-14 mL/min): 1.5-3 g every 24 hours.

Monitoring Recommendations

• Monitor for signs of drug accumulation (neurotoxicity, seizures)
• Consider therapeutic drug monitoring in complex cases
• Assess clinical response to therapy
• Monitor for superinfection, especially with resistant organisms

Important Caveats

• Dosing should be based on ideal body weight
• The total daily dose of sulbactam should not exceed 4 grams
• In severe infections, using the higher end of the dosing range (3 g) may be appropriate
• Drug interactions with other renally eliminated medications should be considered

This dosing strategy aims to maintain therapeutic concentrations while minimizing toxicity risks in this vulnerable patient population.