IV Unasyn (Ampicillin-Sulbactam) Renal Dosing
For patients with renal impairment, reduce the dosing frequency of IV Unasyn based on creatinine clearance: give 1.5-3 grams every 6-8 hours for CrCl ≥30 mL/min, every 12 hours for CrCl 15-29 mL/min, and every 24 hours for CrCl 5-14 mL/min. 1
Dosing Algorithm by Renal Function
Normal to Mild Renal Impairment (CrCl ≥30 mL/min)
- Standard dosing: 1.5-3 grams every 6-8 hours 1
- No adjustment needed as elimination kinetics remain adequate 1
- Maximum sulbactam dose should not exceed 4 grams per day 1
Moderate Renal Impairment (CrCl 15-29 mL/min)
- Adjusted dosing: 1.5-3 grams every 12 hours 1
- Half-life increases to approximately 5 hours (compared to 1 hour in normal function) 1
- Both ampicillin and sulbactam are similarly affected, maintaining their 2:1 ratio 2
Severe Renal Impairment (CrCl 5-14 mL/min)
- Adjusted dosing: 1.5-3 grams every 24 hours 1
- Half-life increases to approximately 9 hours 1
- Terminal half-lives more than double compared to normal renal function 2
Hemodialysis Patients
Critical timing consideration: Administer the dose immediately after hemodialysis, not before 2
- Dosing frequency: Every 24 hours, given post-dialysis 2
- Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam during a 4-hour session 2
- Hemodialysis approximately doubles the total body clearance of both drugs 2
- Administering before dialysis wastes medication and leaves patients undertreated 3
Key Pharmacokinetic Principles
Why the 2:1 Ratio Remains Constant
- Creatinine clearance significantly correlates with total body clearance for both ampicillin (r=0.88) and sulbactam (r=0.54) 2
- Volume of distribution and nonrenal clearance remain unaffected by renal function 2
- The parallel decrease in clearance for both drugs means the same ampicillin-to-sulbactam ratio is appropriate regardless of renal function 2
Population Pharmacokinetic Data
- Creatinine clearance reduces inter-individual variability of drug clearance by 16% 4
- Mean clearance for ampicillin is 10.7 L/h and for sulbactam is 10.4 L/h in patients with community-acquired pneumonia 4
- Body weight affects volume in the peripheral compartment for both drugs 4
Practical Monitoring Considerations
Calculating Creatinine Clearance
When only serum creatinine is available, use the Cockcroft-Gault formula 1:
- Males: [weight (kg) × (140 - age)] / (72 × serum creatinine)
- Females: 0.85 × male value
- Serum creatinine must represent steady-state renal function 1
Patients Requiring Close Monitoring
- Elderly patients (>59 years) are at higher risk of drug toxicity due to age-related decline in renal function 5
- Patients with borderline renal function may require 24-hour urine collection to accurately define the degree of impairment before making regimen changes 6
- Drug accumulation can occur with any degree of renal insufficiency, warranting close monitoring for adverse effects 6
Common Pitfalls to Avoid
- Do not assume all antibiotics require the same degree of dosage adjustment - individualized adjustments based on specific drug properties are necessary 6
- Do not give standard doses in severe renal impairment - the half-life increases from 1 hour to 9 hours, risking significant drug accumulation 1
- Do not administer doses before hemodialysis - this removes the drug prematurely and results in subtherapeutic levels 2
- Do not exceed 4 grams per day of sulbactam regardless of renal function 1