On March 6, 2014, the FDA issued a Drug Safety Communication warning that Shionogi’s antibacterial drug Doribax (doripenem) carries an increased risk of death for patients who develop pneumonia while on ventilators. Approved in 2007, Doribax is indicated for the treatment of complicated intra-abdominal infections and urinary tract infections. Doribax is not approved to treat any type of pneumonia, but may be prescribed off-label for that purpose.
The new FDA warning is an update to a January 2012 statement warning that a clinical trial evaluating the effects of Doribax on treatment of patients with ventilator-associated pneumonia was terminated due to safety concerns. The agency noted that the trial “demonstrated excess mortality and a numerically poorer clinical cure rate among subjects treated with Doribax compared to those treated with imipenem-cilastatin (Primaxin).”
The FDA has approved changes to the Doribax drug label describing this new risk and also explicitly warning that the drug is not approved to treat pneumonia.
Doribax (doripenem) is a synthetic broad-spectrum carbapenem antibiotic. Carbapenems are a class of beta-lactam antibiotics structurally related to penicillin. Other FDA approved carbapenems include: Merrem (meropenem), Invanz (ertapenem), and Primaxin (imipenem and cilastatin).
Of the four drugs evaluated by AdverseEvents that belong to the class of carbapenem antibiotics, Primaxin (imipenem and cilastatin) has the highest RxScore. This signifies an above average level of risk compared to the other drugs in the same class. Doribax (doripenem) had the second highest RxScore among the carbapenems.
To see the RxScores for all of the drugs indicated for the treatment of relapsing forms of multiple sclerosis or to learn more about how RxScore supports comparative drug safety analysis, please login to AdverseEvents Explorer or sign up for a complimentary trial.
AdverseEvents uses a proprietary disproportionality analysis tool called RxSignal to track and predict pending FDA safety actions.
To see the RxSignals for all of the drugs belonging to the class of carbapenem antibiotics or to learn more about how RxSignal supports comparative drug safety analysis, please login to AdverseEvents Explorer or sign up for a complimentary trial.
In our RxSignal analysis, we identified the adverse events listed below as serious safety issues that have not been identified on Doribax’s drug label in either the Warnings & Precautions or Adverse Reactions from Clinical Trial Experience sections. Any of these adverse reactions may trigger further FDA safety reviews.
Using FAERS data (from 11/01/1997 to 12/31/2012), aggregated and standardized by the AdverseEvent RxFilter process, we identified 677 serious adverse events which listed Doribax as a suspect drug. Of these reports, 300 listed Doribax as the primary suspect.
The most commonly reported side effects were convulsion, renal impairment, and sepsis. We identified 95 hospitalizations and 93 patient deaths where Doribax was indicated as the primary suspect.
RxScore is a proprietary algorithmic scoring model based predominantly on post-marketed safety data from over five million FAERS reports. RxScore is presented on a 100-point scale meant to reflect both the breadth and seriousness of side effect(s) by incorporating nine differentially weighted categories including FAERS fields such as “Outcome,” “Event Seriousness,” “Report Type,” and “Event Reporter,” a disproportionality measure, and existing FDA warnings and DEA risk classifications. The score is also negatively adjusted by factoring in both “Condition Seriousness” and a patient’s existing comorbidities. A score of 100 indicates the highest potential adverse event risks.