Overview of seizure-inducing potential of doripenem.
The seizure-inducing potential of carbapenems has been debated since the introduction of imipenem/cilastatin over 20 years ago. Doripenem is a new carbapenem, recently approved in the US for the treatment of adults with complicated urinary tract infections (cUTI) or complicated intra-abdominal infections (cIAI), and additionally in the EU for nosocomial pneumonia, including ventilator-associated pneumonia. Here, the seizure-inducing potential of doripenem is evaluated, using data from in vitro and in vivo animal studies, doripenem clinical trials and doripenem postmarketing reports of seizures. Animal studies indicate that doripenem has low binding affinity for GABA receptors and does not induce seizures at doses greater than seizure-inducing doses of imipenem or meropenem. In clinical studies of cUTI or cIAI, no seizures were reported in the 1332 patients treated with doripenem (500-mg infusion every 8 hours). In two studies, patients with nosocomial pneumonia were treated with doripenem 500 mg (1- or 4-hour infusion every 8 hours), and the incidence of seizures was lower for doripenem (1.2% [6/485]) than imipenem (3.8% [10/263]) or piperacillin/tazobactam (2.7% [6/221]). For patients with seizure-predisposing conditions, seizures occurred during treatment for 3/193 (1.5%) in doripenem, 1/66 (1.5%) in piperacillin/tazobactam and 6/116 (5.2%) in the imipenem group. The review of data from both clinical trials and postmarketing surveillance supports the low seizure-inducing potential of doripenem. The seizure potential of doripenem should be evaluated further in patients at increased risk for seizure.
Zhanel
George G
GG
Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. ggzhanel@pcs.mb.ca
Ketter
Nzeera
N
Rubinstein
Ethan
E
Friedland
Ian
I
Redman
Rebecca
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy; D015780:Carbapenems / Q000009:adverse effects* / Q000627:therapeutic use; D000077726:Doripenem; D006801:Humans; D011358:Product Surveillance, Postmarketing; D016032:Randomized Controlled Trials as Topic; D012640:Seizures / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D055815:Young Adult
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem