Does Merrem (Meropenem) cause nephrotoxicity or impaired renal function?

From the Guidelines

Merrem (Meropenem) can cause nephrotoxicity or impaired renal function, particularly in patients with pre-existing kidney problems or those undergoing renal replacement therapy (RRT). According to a 2019 study published in Critical Care 1, the incidence of acute kidney injury (AKI) in ICU patients is about 40%, and RRT can cause considerable changes in antibiotic pharmacokinetics. The study suggests that therapeutic drug monitoring (TDM) of beta-lactam antibiotics, including meropenem, is necessary in critical care patients undergoing RRT.

Key Considerations

• Meropenem is primarily eliminated by the kidneys, and its clearance can be affected by renal function and RRT techniques 1.
• Patients with pre-existing kidney problems may be at higher risk for kidney effects, and dosage adjustments are typically necessary for patients with renal impairment.
• The mechanism by which meropenem might affect kidneys is not fully understood but may involve direct cellular toxicity to renal tubular cells.
• Kidney function should be monitored during treatment with meropenem, especially in patients receiving prolonged therapy, those with baseline kidney dysfunction, elderly patients, or those taking other medications that can affect kidney function.

Recommendations

• Personalized TDM appears necessary for patients undergoing RRT, as the elimination rate of meropenem can vary depending on the RRT technique and flow rates used 1.
• Healthcare providers should be aware of the potential for nephrotoxicity and monitor kidney function closely in patients receiving meropenem, especially in those with pre-existing kidney problems or undergoing RRT.

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. 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 FDA drug label suggests that Merrem (Meropenem) may cause nephrotoxicity or impaired renal function, particularly in patients with pre-existing renal impairment.

• Key points to consider:
  • Dosage adjustment is necessary in patients with creatinine clearance 50 mL/min or less.
  • The drug is substantially excreted by the kidney, which may increase the risk of adverse reactions in patients with renal impairment.
  • Monitoring of renal function is recommended, especially in elderly patients who are more likely to have decreased renal function 2.

From the Research

Merrem (Meropenem) and Nephrotoxicity

• 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 and those undergoing intermittent haemodialysis (IHD) or various forms of continuous renal replacement therapy (CRRT) 3.
• Studies have shown that meropenem's pharmacokinetics are affected by renal function, with a significant linear relationship between total body clearance and creatinine clearance, as well as between renal clearance and creatinine clearance 4.

Impaired Renal Function and Meropenem

• In patients with impaired renal function, the terminal half-life of meropenem is proportionately increased as renal function decreases 4.
• Haemodialysis has been shown to shorten the elimination half-life of meropenem, from 9.7 h during the predialysis period to 1.4 h during the dialysis period 4.
• A population pharmacokinetic analysis of prolonged meropenem infusion in critically ill CRRT patients found that creatinine clearance significantly influenced meropenem's endogenous clearance 5.

Risk of Nephrotoxicity

• A systematic review found that drug exposure for meropenem is 158% to 286% higher in patients with impaired renal function receiving reduced doses compared to patients with adequate renal function receiving regular doses 6.
• A prospective observational study found that standard meropenem dosing resulted in insufficient meropenem exposure in a considerable fraction of critically ill patients, with mild renal impairment up to augmented renal function identified as a risk factor for target non-attainment 7.
• The study also developed a tool for assessing the risk of target non-attainment for a given renal function and MIC value, known as the MeroRisk Calculator 7.

Dosage Adjustments

• Dosage adjustments are necessary in patients with renal insufficiency and those undergoing IHD or CRRT 3.
• A population pharmacokinetic analysis found that 0.5 g q6h and 1 g q8h may be the optimal regimen for prolonged meropenem infusion in Chinese CRRT patients 5.
• However, the risk of toxicity is very high (>20%) for doses of 2 g q6h and 2 g q8h 5.