What is the recommended dose of meropenem (Carbapenem antibiotic) for a patient with Chronic Kidney Disease (CKD) stage 4 and impaired renal function?

Meropenem Dosing in CKD Stage 4

For patients with CKD stage 4 (creatinine clearance 15-29 mL/min), administer one-half the recommended dose (250 mg for skin/soft tissue infections or 500 mg for intra-abdominal infections) every 12 hours. 1

Dosing Algorithm Based on Creatinine Clearance

The FDA-approved dosing for meropenem in renal impairment follows a clear stepwise reduction based on creatinine clearance 1:

For CKD Stage 4 (CrCl 10-25 mL/min):

• Dose: One-half of the standard recommended dose 1
• Frequency: Every 12 hours 1
• Specific dosing:
  • For complicated skin/soft tissue infections: 250 mg IV every 12 hours 1
  • For intra-abdominal infections: 500 mg IV every 12 hours 1
  • For Pseudomonas aeruginosa infections: 500 mg IV every 12 hours 1

Administration Details:

• Administer as IV infusion over 15-30 minutes 1
• Alternatively, can give as IV bolus over 3-5 minutes for doses up to 1 gram 1

Pharmacokinetic Rationale

The dosing reduction is necessary because meropenem is predominantly renally eliminated 2, 3:

• In patients with CrCl 10-29 mL/min, the elimination half-life extends to approximately 5 hours (compared to 1 hour in normal renal function) 3
• Total body clearance decreases proportionally with declining creatinine clearance 3, 4
• Peak plasma concentrations remain adequate (28-40 mcg/mL) even with dose reduction 4

Critical Caveats

Hemodialysis Considerations:

• The FDA label explicitly states there is inadequate information regarding meropenem use in patients on hemodialysis or peritoneal dialysis 1
• Research data suggests meropenem is significantly removed by hemodialysis (approximately 50% eliminated during a session) 2, 3
• If your patient progresses to dialysis, dosing after each hemodialysis session has been recommended in research studies 3, though this is not FDA-approved guidance

Avoid Underdosing:

• Research demonstrates that approximately 47% of a meropenem dose can be removed during continuous renal replacement therapy 5
• Given meropenem's excellent tolerability profile, underdosing should be avoided as it may lead to treatment failure 2
• For severe infections or Pseudomonas coverage in CKD stage 4, strongly consider using the higher end of the dosing range (500 mg every 12 hours) 1

Monitoring Parameters:

• Calculate creatinine clearance using the Cockcroft-Gault equation (provided in the FDA label) rather than relying on serum creatinine alone 1
• Monitor for CNS adverse effects (seizures) which may be more common in renal impairment 1
• Watch for thrombocytopenia, which has been observed in patients with renal dysfunction 1