Meropenem Dose Adjustment for Creatinine 3.77 mg/dL
For a patient with serum creatinine of 3.77 mg/dL, reduce meropenem to one-half the recommended dose (250 mg for cSSSI or 500 mg for intra-abdominal infections) administered every 12 hours if creatinine clearance is 10-25 mL/min, or every 24 hours if creatinine clearance is less than 10 mL/min. 1
Determining Creatinine Clearance
First, calculate the creatinine clearance (CrCl) using the Cockcroft-Gault equation, as this is the parameter used in the FDA dosing guidelines 1:
- A creatinine of 3.77 mg/dL typically corresponds to severe renal impairment (CrCl likely <30 mL/min in most patients) 2
- Use actual body weight for the calculation, or adjusted body weight if the patient is obese (BMI ≥25 kg/m²) 3
- This level of renal impairment requires urgent evaluation, as it may represent acute kidney injury requiring emergency department referral, particularly if this represents an acute rise 2
FDA-Approved Dosing Adjustments
The meropenem FDA label provides clear dose reduction guidelines based on creatinine clearance 1:
For CrCl 26-50 mL/min:
- Administer the recommended dose (500 mg for cSSSI, 1000 mg for intra-abdominal infections) every 12 hours instead of every 8 hours 1
For CrCl 10-25 mL/min:
- Administer one-half the recommended dose every 12 hours 1
- This means 250 mg every 12 hours for cSSSI or 500 mg every 12 hours for intra-abdominal infections 1
For CrCl <10 mL/min:
- Administer one-half the recommended dose every 24 hours 1
- This means 250 mg every 24 hours for cSSSI or 500 mg every 24 hours for intra-abdominal infections 1
Special Considerations for Pseudomonas aeruginosa
If treating Pseudomonas aeruginosa infections, the standard dose is 1000 mg every 8 hours in patients with normal renal function 1. Apply the same proportional reductions based on creatinine clearance 1:
- CrCl 26-50 mL/min: 1000 mg every 12 hours 1
- CrCl 10-25 mL/min: 500 mg every 12 hours 1
- CrCl <10 mL/min: 500 mg every 24 hours 1
Pharmacokinetic Rationale
The elimination half-life of meropenem increases dramatically with declining renal function 4:
- Normal renal function (CrCl >50 mL/min): half-life approximately 1.5 hours 4
- Moderate impairment (CrCl 30-50 mL/min): half-life approximately 3.4 hours 4
- Severe impairment (CrCl <30 mL/min): half-life approximately 5.0 hours 4
- End-stage renal disease (CrCl <5 mL/min): half-life approximately 7.0 hours 4
Meropenem is primarily eliminated renally, with approximately 48.5% excreted unchanged in urine in patients with normal renal function, decreasing progressively with declining renal function 4.
Critical Pitfalls to Avoid
Do not use standard dosing without adjustment - this creates significant risk of drug accumulation and potential neurotoxicity, including seizures, though seizure risk remains low (0.1%) even in renal impairment 5.
Reassess renal function frequently - in critically ill patients with unstable renal function, meropenem clearance correlates directly with creatinine clearance, and dosing may need adjustment as renal function changes 6, 3.
Consider therapeutic drug monitoring in severe infections - standard dosing in renal impairment may result in subtherapeutic levels for organisms with higher MICs (≥2-8 mg/L), particularly in critically ill patients with augmented renal clearance or those requiring higher pharmacodynamic targets 6.
For patients on hemodialysis, administer the dose after each dialysis session, as hemodialysis significantly removes meropenem (shortening half-life from 7.0 to 2.9 hours) 4.
For patients on continuous venovenous hemofiltration (CVVH), standard renal dosing may be insufficient - consider increasing the dose by 100% as hemofiltration contributes significantly to meropenem elimination (approximately 47% of dose removed) 7.