Pharmacotherapy Newsletter

Volume 1, Issue 39, 10/12/2009

Question

Why does the carbapenem antibiotic, imipenem, require the coadministration of cilastatin in the prevention of its renal inactivation and risk for nephrotoxicity but doripenem, ertapenem and meropenem do not?

Answer

The carbapenem class of antibiotics have increased in number over the past few years to now include four options on the market for clinicians to use.  The current carbapenem antibiotics include doripenem (Doribax®), ertapenem (Invanz®), imipenem/cilastatin (Primaxin®), and meropenem (Merrem®).^1-4  With the exception of meropenem, the others are all approved for urinary tract infections (UTI).^1-4  A quick review of these available product names reveals that imipenem is the only carbapenem that requires the use of cilastatin.  Many experienced clinicians know that cilastatin is required with the use of imipenem for two main reasons.  The first is to avoid the inactivation of imipenem once it gets secreted into the proximal renal tubule of the kidney by the enzyme dehydropeptidase (DHP)-1.^3,5,6  The inactivation of imipenem within the renal tubule would obviously render the drug ineffective for the treatment of UTI.^5-7  The second is due to the increase risk for nephrotoxicity of imipenem metabolites once metabolized by DHP-1.⁸