Meropenem Dosing in Chronic Kidney Disease
For patients with CKD, meropenem requires dose reduction when creatinine clearance falls below 50 mL/min, with the specific regimen depending on the degree of renal impairment and infection severity. 1
Standard Dosing Adjustments by Creatinine Clearance
The FDA-approved dosing schedule for meropenem in renal impairment is straightforward and based on creatinine clearance (CrCl): 1
CrCl >50 mL/min: No adjustment needed—use standard dose (500 mg every 8 hours for complicated skin/soft tissue infections; 1 gram every 8 hours for intra-abdominal infections) 1
CrCl 26-50 mL/min: Administer the full recommended dose but extend the interval to every 12 hours 1
CrCl 10-25 mL/min: Reduce dose to one-half the recommended dose and give every 12 hours 1
CrCl <10 mL/min: Reduce dose to one-half the recommended dose and extend interval to every 24 hours 1
Pharmacokinetic Rationale
The need for dose adjustment stems from meropenem's predominantly renal elimination pathway: 2
In healthy volunteers, approximately 80% of absorbed meropenem is cleared renally, with only 20% undergoing nonrenal clearance 2
The terminal half-life increases dramatically from 0.9 hours in normal renal function to 6.8 hours in end-stage renal disease 2
Total plasma clearance correlates linearly with GFR, decreasing from 186 mL/min/1.73 m² in normal function to 19 mL/min/1.73 m² in severe renal impairment 2
As renal function declines to CrCl 5-29 mL/min, nonrenal clearance increases to approximately 50% of total elimination, but this compensatory mechanism is insufficient to prevent drug accumulation 2
Infection-Specific Considerations
For Pseudomonas aeruginosa infections, higher doses are required even with renal impairment: 1
When CrCl >50 mL/min: Use 1 gram every 8 hours (not 500 mg) for complicated skin/soft tissue infections caused by P. aeruginosa 1
Apply the same proportional reductions outlined above when CrCl <50 mL/min, but start from the 1 gram base dose 1
Hemodialysis Patients
There is inadequate information regarding meropenem use in patients on hemodialysis or peritoneal dialysis according to FDA labeling, creating a significant knowledge gap 1. However, research data provides some guidance:
Meropenem is readily dialyzable, with approximately 50% removed during intermittent hemodialysis sessions 3, 2
Dialysis clearance is approximately 79-81 mL/min/1.73 m² for both meropenem and its metabolite 2
During sustained low-efficiency dialysis (SLED), mean plasma concentration reduction is 79% over an 8-hour session, with significantly more removal in the first 4 hours 4
Research suggests dosing 1 gram every 12 hours during typical 8-hour SLED sessions maintains adequate plasma concentrations (mean trough 4 μg/mL) when targeting MIC ≤2 μg/mL 4
For patients on prolonged intermittent renal replacement therapy, continuous infusion of 2 grams per day has been reported as effective, though this approach requires further validation 5
Critical Pitfalls to Avoid
Do not use standard dosing in moderate-to-severe CKD, as meropenem exposure increases more than 10-fold in end-stage renal disease compared to normal function 2. This creates unnecessary risk of adverse effects without additional therapeutic benefit 2.
Calculate creatinine clearance using the Cockcroft-Gault equation (provided in FDA labeling) rather than relying solely on serum creatinine, as the latter significantly underestimates the degree of renal impairment needed for dose adjustment 1.
Monitor for accumulation of the inactive metabolite ICI 213,689, which has a half-life of 23.6 hours in CrCl 5-29 mL/min and shows minimal decline over 48 hours in end-stage renal disease 2. While this metabolite lacks antibacterial activity, its accumulation may have unknown clinical significance 2.
Recent PBPK modeling confirms that dosing regimens require further individualization beyond standard FDA recommendations, particularly in CKD patients where meropenem exposure increases progressively with declining kidney function 6. The established models successfully predict pharmacokinetics and support the need for personalized dosing strategies 6.