What are the considerations for using Meropenem (generic name) in elderly patients with Impaired renal function?

From the Guidelines

Meropenem dosing should be reduced in elderly patients with decreased renal function to minimize the risk of toxicity and optimize treatment outcomes. For elderly patients with creatinine clearance (CrCl) 26-50 mL/min, administer 1 gram every 12 hours; for CrCl 10-25 mL/min, give 500 mg every 12 hours; and for CrCl less than 10 mL/min, give 500 mg every 24 hours 1.

Key Considerations

• Monitor renal function regularly during treatment, as elderly patients often experience age-related decline in kidney function that may not be reflected in serum creatinine levels alone.
• Watch for adverse effects including seizures, which occur more frequently at higher doses and in patients with renal impairment.
• Consider using the Cockcroft-Gault equation with actual body weight to calculate creatinine clearance, but be aware this may overestimate renal function in frail elderly patients.
• Therapeutic drug monitoring may be beneficial in critically ill elderly patients to ensure optimal dosing, as supported by recent guidelines for the diagnosis, treatment, prevention, and control of infections caused by carbapenem-resistant gram-negative bacilli 1.

Rationale

The pharmacokinetics and pharmacodynamics of renally excreted drugs like meropenem are altered in patients with impaired renal function, necessitating dose adjustment to prevent toxicity 1.

Supporting Evidence

• A study published in the Journal of Microbiology, Immunology and Infection in 2023 highlights the importance of therapeutic drug monitoring in optimizing dosing regimens and reducing adverse reactions 1.
• The age-related decline in renal function, with a loss of renal cortical mass and a decrease in glomerular filtration rate, supports the need for individualized assessment and dose adjustment in elderly patients 1.

From the FDA Drug Label

Meropenem is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function A pharmacokinetic study with meropenem for injection in elderly patients has shown a reduction in the plasma clearance of meropenem that correlates with age-associated reduction in creatinine clearance [see Clinical Pharmacology (12.3)]. Dosage adjustment is necessary in patients with creatinine clearance 50 mL/min or less [see Dosage and Administration (2. 2), Warnings and Precautions (5.8), and Clinical Pharmacology (12. 3)].

Key Considerations:

• Dose adjustment is necessary in elderly patients with low renal function (creatinine clearance 50 mL/min or less) to minimize the risk of adverse reactions.
• Monitoring renal function is recommended in elderly patients receiving meropenem.
• Reduced plasma clearance of meropenem has been observed in elderly patients, which may increase the risk of adverse reactions 2.

From the Research

Meropenem Pharmacokinetics in the Elderly with Low Renal Function

• Meropenem is a carbapenem antibacterial with a wide spectrum of activity against Gram-positive and Gram-negative bacteria, including beta-lactamase producers and Pseudomonas aeruginosa 3.
• The drug is predominately excreted unchanged in the urine, and thus dosage adjustments are necessary in patients with renal insufficiency 3.
• In patients with renal failure, the half-life of meropenem is prolonged up to 13.7 hours, and plasma meropenem concentrations are influenced by drug-specific factors as well as membrane and treatment modalities 3.

Impact of Renal Function on Meropenem Exposure

• A study found a strong relationship between renal function and meropenem concentrations, with a correlation coefficient of -0.7 (p-value < 0.001) 4.
• Patients with severe and moderate renal impairment had higher dose-normalized meropenem exposure compared to those with normal or hyperfiltrating renal function 4.
• Another study found that mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment in patients with meropenem-treated infections 5.

Dosing Regimens in Patients with Low Renal Function

• Recommended meropenem dosing regimens may be suboptimal in patients with normal or augmented renal clearance, and modified dosing or infusion modalities may be necessary to achieve appropriate MIC coverage 6.
• A systematic review and Monte Carlo simulations found that a regimen of 750 mg q 8 h was the optimal dose for pre-dilution continuous venovenous hemofiltration and continuous venovenous hemodialysis modality using two effluent rates (25 and 35 mL/kg/h) 7.
• Therapeutic drug monitoring (TDM) can help optimize dosing and minimize the risk of antibiotic resistance, especially in patients with renal alterations despite standard dose adaptations 4.