Ceftum (Cefuroxime) Dose Adjustment in CKD
Cefuroxime requires mandatory dose reduction in patients with chronic kidney disease based on creatinine clearance, with specific adjustments outlined in the FDA labeling that must be followed to prevent drug accumulation and toxicity. 1
Dose Adjustment Algorithm
The FDA-approved dosing regimen for cefuroxime in renal impairment is stratified by creatinine clearance (CrCl) 1:
Standard Dosing by Renal Function:
CrCl >20 mL/min: 750 mg to 1.5 grams every 8 hours (no adjustment needed) 1
CrCl 10-20 mL/min: 750 mg every 12 hours (extend interval) 1
CrCl <10 mL/min: 750 mg every 24 hours 1
Hemodialysis patients: Give supplemental 750 mg dose after each dialysis session 1
Critical Implementation Points
Calculating Creatinine Clearance:
The Cockcroft-Gault formula should be used for dose adjustments, as this is what drug labeling and clinical studies are based on 1, 2. The formula accounts for age, weight, and sex 1:
- Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)] 1
- Females: 0.85 × male value 1
Pharmacokinetic Rationale:
Cefuroxime is primarily eliminated by glomerular filtration without significant metabolism 3, 4. In renal impairment, the elimination half-life increases substantially, leading to drug accumulation if doses are not adjusted 4, 5. The dosing strategy extends the interval between doses rather than reducing the dose amount, which helps maintain adequate peak concentrations for bactericidal activity 1.
Monitoring Requirements
Renal function should be monitored during therapy, especially in seriously ill patients receiving maximum doses 1. Key monitoring parameters include:
- Serum creatinine to assess stable renal function before calculating CrCl 1
- Clinical response and signs of drug accumulation 1
- Evaluation for superinfection with prolonged use 1
Special Populations and Precautions
Elderly Patients:
Elderly patients (>59 years) are at higher risk of drug toxicity due to age-related decline in renal function 6. The Cockcroft-Gault formula automatically adjusts for age, but additional clinical vigilance is warranted 1.
Dialysis Considerations:
- Hemodialysis: Cefuroxime is dialyzable, requiring a supplemental dose after each dialysis session 1, 3
- Peritoneal dialysis: For chronic peritoneal dialysis, a loading dose of 10 mg/kg followed by 5 mg/kg into each dialysis cavity has been used for similar cephalosporins 3
Concurrent Nephrotoxic Medications:
Cephalosporins should be given cautiously with potent diuretics or aminoglycosides, as these combinations may adversely affect renal function 1. Nephrotoxicity has been reported with concomitant aminoglycoside use 1.
Common Pitfalls to Avoid
- Do not use reduced doses without extending intervals - this compromises bactericidal activity 1
- Do not use MDRD or CKD-EPI formulas for dosing - drug labeling is based on Cockcroft-Gault 1, 2
- Do not forget post-dialysis supplementation - failure to replace dialyzed drug leads to subtherapeutic levels 1
- Do not assume stable renal function - serum creatinine should represent steady-state before calculating CrCl 1
Duration of Therapy
Continue therapy for a minimum of 48-72 hours after the patient becomes asymptomatic or bacterial eradication is documented 1. For streptococcal infections, a minimum of 10 days is required to prevent rheumatic fever or glomerulonephritis 1.