Pharmacy & Therapeutics - October 2008 - (Page 564)

DORIBAX™ DORIBAX™ (doripenem for injection) clinical studies; in some patients, parenteral therapy was followed by a switch to an oral antimicrobial. [see Clinical Studies (14) in full Prescribing Information] The median age of patients treated with DORIBAXTM was 54 years (range 18-90) in the comparative cUTI study and 46 years (range 18-94) in the pooled comparative cIAI studies. There was a female predominance (62%) in the comparative cUTI study and a male predominance (63%) in the pooled cIAI studies. The patients treated with DORIBAXTM were predominantly Caucasian (77%) in the three pooled phase 3 studies. The most common adverse reactions (≥5%) observed in the DORIBAXTM phase 3 clinical trials were headache, nausea, diarrhea, rash and phlebitis. During clinical trials, adverse drug reactions that led to DORIBAXTM discontinuation were nausea (0.2%), vulvomycotic infection (0.1%) and rash (0.1%). Adverse reactions due to DORIBAXTM 500 mg q8h that occurred at a rate ≥1 % in either indication are listed in Table 1. Hypersensitivity reactions related to intravenous study drug and C. difficile colitis occurred at a rate of less than 1% in the three controlled phase 3 clinical trials. Table 1: Adverse Reactions† with Incidence Rates (%) of ≥1% and Adverse Events†† Having Clinically Important Differences in Frequency by Indication in the Three Controlled, Comparative DORIBAXTM Phase 3 Clinical Trials Complicated Urinary Tract Infections (one trial) System organ class DORIBAXTM Levofloxacin 500 mg 250 mg IV q8h q24h (n =376 ) (n = 372) Complicated IntraAbdominal Infections (two trials) DORIBAXTM Meropenem 500 mg 1g q8h q8h (n = 477) (n = 469) (doripenem for injection) for Intravenous Infusion Brief Summary: The following is a brief summary only. Before prescribing, see complete Prescribing Information in DORIBAXTM (doripenem for injection) labeling. To reduce the development of drug-resistant bacteria and maintain the effectiveness of DORIBAXTM and other antibacterial drugs, DORIBAXTM 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. CONTRAINDICATIONS DORIBAXTM is contraindicated in patients with known serious hypersensitivity to doripenem or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: 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. Before therapy with DORIBAXTM is instituted, careful inquiry should be made to determine whether the patient has had a previous hypersensitivity reaction to other carbapenems, cephalosporins, penicillins or other allergens. If this product is to be given to a penicillin- or other beta-lactam-allergic patient, caution should be exercised because cross-hyperreactivity among beta-lactam antibiotics has been clearly documented. If an allergic reaction to DORIBAXTM occurs, discontinue the drug. Serious acute hypersensitivity (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. Interaction with Sodium Valproate: 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. [see Drug Interactions] Clostridium difficile-Associated Diarrhea: Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. 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 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. [see Adverse Reactions] Development of Drug-Resistant Bacteria: Prescribing DORIBAXTM in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Pneumonitis with Inhalational Use: When DORIBAXTM has been used investigationally via inhalation, pneumonitis has occurred. DORIBAXTM should not be administered by this route. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of labeling: • Anaphylaxis and serious hypersensitivity reactions [see Warnings and Precautions] • Interaction with sodium valproate [see Warnings and Precautions and Drug Interactions] • Clostridium difficile-associated diarrhea [see Warnings and Precautions] • Development of drug-resistant bacteria [see Warnings and Precautions] • Pneumonitis with inhalational use [see Warnings and Precautions] Adverse Reactions from Clinical Trials: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice. During clinical investigations, 853 adult patients were treated with DORIBAXTM IV (500 mg administered over 1 hour q8h) in the three comparative phase 3 Nervous system disorders Headache Vascular disorders Phlebitis Gastro-intestinal disorders Nausea Diarrhea Blood and Lymphatic System Disorders Anemia†† Renal and Urinary Disorders Renal impairment/ Renal failure†† 16 4 15 4 4 8 5 6 4 6 6 10 12 11 9 11 <1

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Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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