From the FDA Drug Label
DOSAGE AND ADMINISTRATION The dosage of Imipenem and Cilastatin for Injection (I.V.) in adult patients should be based on suspected or confirmed pathogen susceptibility ( 2.1). For adult patients with normal renal function (creatinine clearance of greater than or equal to 90 mL/min), the recommended dosage regimens are: 500 mg every 6 hours OR 1,000 mg every 8 hours OR 1,000 mg every 6 hours ( 2. 1). A reduction in dose must be made for a patient with a creatinine clearance of less than 90 mL/min ( 2.3). Patients with creatinine clearances of less than 15 mL/min should not receive Imipenem and Cilastatin for Injection (I.V.) unless hemodialysis is instituted within 48 hours ( 2. 4).
- Dose reduction is required for patients with creatinine clearance less than 90 mL/min.
- The exact dose for patients with CKD is not specified, but a reduction from the normal dose is necessary.
- For patients with creatinine clearance less than 15 mL/min, the drug should not be administered unless hemodialysis is instituted within 48 hours 1.
From the Research
Imipenem dosing should be reduced in chronic kidney disease (CKD) based on creatinine clearance (CrCl), with the most recent and highest quality study suggesting that a shorter dosing interval is beneficial in patients with impaired renal function. For patients with CrCl 41-70 mL/min, administer 500 mg every 6-8 hours; for CrCl 21-40 mL/min, give 250-500 mg every 8 hours; for CrCl 6-20 mL/min, give 250 mg every 12 hours; and for CrCl less than 5 mL/min, give 250 mg every 12 hours 2. Imipenem is typically combined with cilastatin (as Primaxin) to prevent renal metabolism of imipenem. Hemodialysis removes imipenem, so doses should be scheduled after dialysis sessions, with a supplemental dose potentially needed after dialysis. Careful monitoring for seizures is important, especially in patients with CNS disorders or renal impairment, as imipenem can lower the seizure threshold. Dose adjustments are crucial because imipenem is primarily eliminated by the kidneys, and inadequate adjustment in CKD patients can lead to drug accumulation and increased risk of adverse effects including seizures and neurotoxicity. Some key points to consider when dosing imipenem in CKD patients include:
- The importance of adjusting the dose based on CrCl to minimize the risk of adverse effects
- The need to monitor for seizures, especially in patients with CNS disorders or renal impairment
- The potential for hemodialysis to remove imipenem, requiring supplemental doses after dialysis
- The benefits of using a shorter dosing interval in patients with impaired renal function, as suggested by the most recent and highest quality study 2. It is also important to note that imipenem has a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including extended-spectrum β-lactamase (ESBL) and Amp-C β-lactamase producing Enterobacteriaceae and anaerobes, but resistance to imipenem may emerge during treatment of P. aeruginosa infections 3. Overall, careful consideration of the patient's renal function and careful monitoring for adverse effects are crucial when dosing imipenem in CKD patients.