From the Guidelines
Meropenem requires dose adjustment in elderly patients with reduced renal function to prevent side effects, and the dosage should be adjusted based on creatinine clearance to minimize the risk of toxicity. For elderly patients with creatinine clearance 26-50 mL/min, the standard dose should be reduced to 1 gram every 12 hours; for clearance 10-25 mL/min, 500 mg every 12 hours; and for clearance below 10 mL/min, 500 mg every 24 hours 1. Common side effects in this population include diarrhea, nausea, headache, and injection site reactions, but elderly patients with impaired kidneys are at higher risk for neurotoxicity, including confusion, hallucinations, and seizures, as well as electrolyte disturbances, particularly hypokalemia and sodium abnormalities 1.
Key Considerations
- Renal function decline is common in the elderly, with a 1% reduction in renal function per year beyond age 30-40, resulting in a potential 40% decline by age 70 1.
- The pharmacokinetics and pharmacodynamics of renally excreted drugs, such as meropenem, are altered in patients with impaired renal function, necessitating dose adjustment to prevent toxicity 1.
- Close monitoring of renal function, neurological status, and electrolytes is essential during treatment with meropenem in elderly patients with reduced renal function 1.
- The SIOG Task Force on Renal Safety in the Elderly advocates for dose adjustment of renally cleared drugs and avoidance of nephrotoxic agents whenever possible 1.
Monitoring and Management
- Regular renal monitoring is warranted in elderly cancer patients, particularly those receiving renally cleared or nephrotoxic drugs 1.
- Renal function should be assessed at least by calculation of creatinine clearance (CrCl) in every patient, even when serum creatinine (SCr) is within the normal range 1.
- Elderly patients with impaired kidneys are at higher risk for meropenem-induced side effects, and close monitoring is essential to minimize this risk 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)].
The elderly with low renal function may experience increased risk of adverse reactions due to meropenem's substantial excretion by the kidney. Key considerations include:
- Dose selection: Care should be taken when selecting a dose for elderly patients with low renal function.
- Renal function monitoring: It may be useful to monitor renal function in these patients.
- Dosage adjustment: Adjustment is necessary for patients with creatinine clearance 50 mL/min or less 2.
From the Research
Meropenem Side Effects 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 can vary significantly depending on the treatment modality 3
Renal Function Considerations in the Elderly
- Renal function declines with age, with an average decline of 10 mL/min in glomerular filtration rate every 10 years after the age of 40 4
- Serum creatinine alone is not a reliable indicator of renal function, and estimated glomerular filtration rate (eGFR) should be used to assess renal function 4
- The Cockcroft-Gault equation can be used to adjust medicine doses in patients with chronic renal impairment 4
Drug Dosing Considerations in the Elderly with Chronic Kidney Disease
- Chronic kidney disease is a common disorder in the elderly, and pharmacologic management of diseases in this population can be challenging 5
- Primary care providers must proceed with caution when prescribing drugs for elderly patients with kidney disease, as renal impairment can cause medicines to accumulate or cause toxicity 5
- The choice of literature source can have a significant impact on drug management, and efforts should be deployed to standardize methods for estimating kidney function in geriatric patients and literature recommendations on drug dose adjustment in renal failure 6
Meropenem Dosing Regimens in Critically Ill Patients with Renal Impairment
- Meropenem plasma concentration above a pathogen's MIC over the whole dosing interval (100% ƒT>MIC) is a determinant of outcome in severe infections 7
- Recommended meropenem regimens may be suboptimal in ICU patients with normal or augmented renal clearance, and modified dosing or infusion modalities may be necessary to achieve appropriate MIC coverage 7
- Patients with CLCR <60 mL/min may require adjusted dosing regimens to achieve appropriate coverage, while patients with CLCR ≥90 mL/min may require increased dose, frequency of administration, and infusion duration, or continuous infusion 7