Raritan, NJ – May 15, 2008 – The investigational use of doripenem for the treatment of ventilator-associated pneumonia (VAP) was associated with shorter patient length of stay and reduced hospital resource utilization, according to new data published in the April edition of Clinical Therapeutics. The total number of hospital days and time on mechanical ventilation were significantly shorter for patients treated with doripenem compared to the commonly used imipenem-cilastatin in exploratory analyses from a Phase III pivotal trial evaluating the safety and effectiveness of doripenem in the treatment of VAP.
Mechanical ventilation often is initiated in hospital patients who are too weak to breathe on their own. VAP, an infection that usually develops 48-72 hours or more after mechanical ventilation is initiated, is the most common infection found in the intensive care units (ICU), accounting for 47% of all infections in the ICU. With 300,000 new cases in the U.S. each year and a cost of approximately $40,000 per case, VAP can have a serious impact on hospital resources.
Hospital resource utilization was collected as a part of a large, multinational, Phase III study conducted by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., (J&JPRD) that compared doripenem (500mg infused over four hours, three times a day) to imipenem-cilastatin (500mg infused over one hour, four times a day, or 1000mg infused over one hour, three times a day) among 501 patients with VAP. The median length of stay was significantly shorter in patients treated with doripenem compared to imipenem-cilastatin (22 days versus 27 days, respectively; p=0.0102) and time on mechanical ventilation was significantly shorter for patients treated with doripenem compared to imipenem-cilastatin (7 days versus 10 days, respectively; p=0.0338). Clinical cure rates were similar for both patients taking doripenem and imipenem-cilastatin.
“VAP remains a major challenge and is associated with substantial mortality, mobidity and cost. Few interventions have been shown to decrease the length of stay for patients with VAP,” said Andrew F. Shorr, MD, MPH, Associate Director, Pulmonary and Critical Care, Washington Hospital Center and Associate Professor of Medicine, Georgetown University. “Any new intervention that alters length of stay of this serious disease has the opportunity to improve outcomes and to limit overall costs given the average cost for treating VAP approaches $40,000 per patient.”
Doripenem, marketed as DORIBAX™ (doripenem for injection) in the U.S., is an intravenous antibiotic approved for use in the treatment for complicated intra-abdominal and complicated urinary tract infections. The use of DORIBAX for the treatment of nosocomial pneumonia (pneumonia acquired in the hospital), including VAP, currently is under regulatory review in the U.S., E.U. and other countries. DORIBAX is not approved for the treatment of nosocomial pneumonia. The use of DORIBAX for the treatment of complicated intra-abdominal and complicated urinary tract infections also is under regulatory review in the E.U. and other countries.
DORIBAX belongs to a class of antibacterial drugs called carbapenems, which are important to treat serious – and sometimes life-threatening – infections caused by a broad range of bacteria characterized as Gram-negative and Gram-positive, based on a classification process that is used to identify the specific type of bacteria.
DORIBAX is currently marketed to U.S. hospitals by Ortho-McNeilTM, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. and is licensed from Shionogi & Co., Ltd. Andrew F. Shorr, MD, MPH is a paid consultant to Ortho-McNeil.
INDICATIONS
DORIBAX is indicated as a single agent for the treatment of: complicated intra-abdominal infections caused by susceptible strains of E. coli, K. pneumoniae, P. aeruginosa, B. caccae, B. fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, S. intermedius, S. constellatus or P. micros, and for the treatment of complicated urinary tract infections, including pyelonephritis, caused by susceptible strains of E. coli, including cases with concurrent bacteremia, K. pneumoniae, P. mirabilis, P. aeruginosa, or A. baumannii.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of DORIBAX and other antibacterial drugs, DORIBAX should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting and modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
IMPORTANT SAFETY INFORMATION
DORIBAX is contraindicated in patients with known serious hypersensitivity to doripenem or other carbapenems or in patients who have demonstrated anaphylactic reactions to beta-lactams.
Serious and occasionally fatal hypersensitivity (anaphylactic) and serious skin reactions have been reported in patients receiving beta-lactam antibiotics. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. If an allergic reaction to DORIBAX occurs, discontinue the drug. Serious acute anaphylactic reactions require emergency treatment with epinephrine and other emergency measures, including oxygen, IV fluids, IV antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated.
Carbapenems may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations cannot be maintained in the therapeutic range or seizures occur.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two (2) months after administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.
When doripenem has been used investigationally via inhalation, pneumonitis has occurred. DORIBAX should not be administered by this route.
Safety and effectiveness in pediatric patients have not been established. The most common adverse reactions (³5%) observed in clinical trials were headache, nausea, diarrhea, rash and phlebitis.
J&JPRD is a wholly-owned subsidiary of Johnson & Johnson, the world's most broadly-based producer of health care products. J&JPRD is headquartered in Raritan, N.J., and has facilities throughout Europe, the United States and Asia. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas, including CNS, Internal Medicine and Oncology, to address unmet medical needs worldwide.
For more information, visit the Johnson & Johnson Pharmaceutical Research & Development Web site at www.jnjpharmarnd.com.
The Ortho-McNeilTM, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., is committed to providing innovative, high-quality prescription medicines and resources for healthcare providers and their patients in hospitals and other care facilities. For more information, visit www.ortho-mcneil.com.
For more information about DORIBAX, please visit www.DORIBAX.com.
Journal
Clinical Therapeutics