Overview of Seizure-Inducing Potential of Doripenem

  title={Overview of Seizure-Inducing Potential of Doripenem},
  author={George G. Zhanel and Nzeera Ketter and Ethan Rubinstein and Ian R. Friedland and Rebecca Redman},
  journal={Drug Safety},
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… 

Safety of intravenous infusion of doripenem.

  • R. RedmanT. File
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2009
Overall, intravenous doripenem was found to be safe and well tolerated, demonstrating a safety profile comparable to that of comparator agents and a limited propensity to induce seizures, including when administered via 1-h or 4-h infusion.

Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations

Data indicate that carbapenem‐associated seizure is best managed with benzodiazepines, followed by other agents that enhance GABA transmission, and the combination should be avoided whenever possible.

The risk of seizures among the carbapenems: a meta-analysis.

Although imipenem was more epileptogenic than non-carbapenem antibiotics, there was no statistically significant difference in the imipanem versus meropenem head-to-head comparison.

Use of doripenem and risk of seizure and renal impairment in US hospitalized patients: a retrospective cohort study

In this large retrospective cohort study of US hospitalized patients, no statistically significant differences in the adjusted relative rates of renal impairment/failure and seizure were observed between doripenem and a propensity score-matched comparator cohort of imipenems IV patients in the treatment of cUTI and cIAI.


Assessment of the relative strengths and weaknesses of carbapenems by considering their microbiological, clinical, pharmacokinetics and pharmacokinetic/pharmacodynamic properties and defining optimal conditions of uses suggests that Maximizing clinical outcomes and minimizing antibiotic resistance using individualized doses may be best achieved with therapeutic drug monitoring.

Pharmacokinetic-Pharmacodynamic-Model-Guided Doripenem Dosing in Critically Ill Patients

Results of pharmacokinetics/pharmacodynamics (PK/PD) modeling can guide dose optimization, thereby potentially increasing the clinical efficacy of doripenem against serious Gram-negative bacterial infections.

Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review

The onset of disturbed vigilance, myoclonus, and/or seizure in a patient taking β-lactam antibiotics, especially if associated with renal insufficiency or underlying brain abnormalities, should lead physicians to suspect adverse drug reactions and to consider changes in antibacterial therapy.

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter, however, prolonged infusions should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC.

Neurological and Psychiatric Adverse Effects of Antimicrobials

The different neurotoxic effects of a range of antimicrobials are highlighted, proposed mechanisms of onset are discussed and general management recommendations are offered.



Safety of Imipenem/Cilastatin in Neurocritical Care Patients

When dosed appropriately, imipenem/cilastatin may be used to treat serious infections in critically ill patients with central nervous system (CNS) disorders or injury with minimal seizure risk, and cautious use is warranted.

Carbapenems in Serious Infections

Using a carbapenem instead of a cefalosporin for empirical treatment of life-threatening infections is that both imipenem/cilastatin and meropenem have a broader spectrum of activity and are more resistant to hydrolysis by the most common β-lactamases.

Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open-label, multicenter study.

Doripenem was clinically and microbiologically effective in patents with NP, including those with early-onset ventilator-associated pneumonia, and was therapeutically noninferior to piperacillin/tazobactam.

Safety profile of meropenem: a review of nearly 5,000 patients treated with meropenem.

This new safety analysis includes data from 46 clinical trials in hospitalized patients with serious bacterial infections and supports the previous findings that meropenem has a favourable and acceptable safety profile.

Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: A multicenter, randomized study*

In this large, phase III study of patients with ventilator-associated pneumonia, a 4-hr intravenous infusion of doripenem was clinically efficacious and therapeutically noninferior to imipenems.

Two decades of imipenem therapy.

The factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago are reviewed.


Results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the Hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of V PA.