Product
Doribax

Approval Date
October 12, 2007
 
Release Date
November 29, 2007
 
Company
Ortho-McNeil
 
Class
Antibiotic (carbapenem)
 
Indication
Susceptible complicated intra-abdominal and complicatedurinary tract infections (including pyelonephritis).
 
Active Ingredient
Doripenem (as monohydrate) 500mg/vial; pwd; for IV infusionafter constitution and dilution; preservative-free.
 
Agency Roster
Carbon (professional)

The FalkGroup, LLC

 
MarketingStrategy/Execution
Doribax was launched in November asa single-agent, injectable treatment for complicated intra-abdominal andcomplicated urinary tract infections. Ortho-McNeil is marketing the drug tohospitals and other healthcare facilities through its Institutional Franchise. Product messaging is likely to stressthat it’s one of few antibiotics available for treating life-threateningGram-negative infections—an unmet need in the hospital market. The company is pursuing another indication for treatinghospital-acquired (nosocomial) pneumonia, including ventilator-associatedpneumonia. With few branded products left in the market for drugs to treat community-acquired infections, the main commercialopportunity in antibacterials may lie in treating nosocomial infections, which represented a $6.7-billion market in2005, according to Datamonitor. At the approved dose, Doribax demonstrated a curerate comparable to levofloxacin (Ortho’s quinolone Levaquin) for complicated UTIs and to meropenem (AstraZeneca’s carbapenem Merrem) forcomplicated intra-abdominal infections. Ortho-McNeil in-licensed doripenem from Japan’s Shionogi, and another in-licensed antibacterial, ceftobiprole from Basilea, was filed in May 2007.

The Market

UT ANTNFCT US sales ($000s) last 5 years

2006

$165,412

2005

$190,071

2004

$212,951

2003

$270,961

2002

$227,040

Source: IMS Health, Oct. 2007

Top 5 UT ANTNFCT

 

Jan.-Oct. ’07 US sales ($000s)

% sales growth over Jan.-Oct. ‘06

NITROFURANT MACRO

$48,225

-10%

NITROFURANT MONO/M

$27,964

-8%

FURADANTIN (Sciele)

$16,720

19%

PROSED/DS (Allergan)

$5,455

131%

MACRODANTIN (Procter & Gamble)

$4,805

-3%

Source: IMS Health, Oct. 2007

Physician Outlook
Doribax(doripenem) was approved in October 2007. It belongs to the carbapenem class ofantibacterial agents used to treat gram-positive and gram-negative bacterialinfections. Six months prior to launch, 25% of physicians participating in GfKMarket Measures’ 2007 Hospital Injectable Antibiotics studies were aware ofdoripenem, which is higher than the 18% norm for awareness across all pipelineproducts. It is anticipated to be an important treatment for hospitalsetting infections, receiving a 5.02 rating (on a 7-point scale) foranticipated importance.

—SueRamspacher, senior VP, category business leader, anti-infectives, GfK MarketMeasures, Dec. 2007
 
Also in the Pipeline(according to Adis R&D Insight)
No competitor products in phase III or pre-registration, US
 
Recent MM&MCoverage
CommonHealthdissolves professional shop
Product News

The Top 60:Carbon

J&Jconsolidation splits Rx brands between two holding companies

Medical/SurgicalJournal Ad Review

SpecialtySpiral


Pharmacology
Doripenem is a carbapenem antibiotic that has shown to beactive against aerobic and anaerobic Gram (–) and Gram (+) bacteria. Itinactivates multiple essential penicillin-binding proteins resulting in theinhibition of cell wall synthesis with subsequent cell death. It is stable tohydrolysis by most beta-lactamases produced by Gram (+) and Gram (–) bacteria.
Doripenem has been shown to have activity against A. baumannii,E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, S. constellatus, S.intermedius, B. caccae, B. fragilis, B. thetaiotaomicron, B. uniformis, B.vulgatus, and P. micros. Although cross-resistance may occur, somebacterial isolates that are resistant to other carbapenems may be susceptibleto doripenem.

Clinical Trials

Two double-blind studies involving 946 adults withcomplicated intra-abdominal infections (eg, appendicitis, bowel perforation,cholecystitis, intra-abdominal or solid organ abscess, peritonitis) wereconducted to compare doripenem and meropenem. Both regimens allowed the optionto switch to oral amoxicillin/clavulanate after 3 days of IV therapy with the studydrugs for a total of 5–14 days of IV and oral treatment. Doripenem was shown tobe non-inferior to meropenem in regard to clinical cure rates in patients withsusceptible pathogens isolated at baseline and no major protocol deviations attest of cure visit 25–45 days after completion of therapy. It was alsonon-inferior to meropenem in patients with baseline pathogens isolatedregardless of susceptibility.

Two multicenter, randomized studies compared doripenem tolevofloxacin in 1171 adults with complicated UTIs. One was a double-blindstudy, and the other was a noncomparative study. Both allowed the option ofswitching to oral levofloxacin after at least 3 days of IV therapy for a totalof 10 days of treatment. Patients with bacteremia were allowed to receivelevofloxacin for a total of 10–14 days. Doripenem was shown to be non-inferiorto levofloxacin with regard to microbiological eradication rates in patientswith baseline pathogens, no major protocol deviations, and urine cultures atthe test of cure visit 5–11 days after completing therapy. It was alsonon-inferior in patients with pretreatment urine cultures.

Adverse Reactions

Headache, nausea, diarrhea (may be serious; evaluate ifoccurs), rash, phlebitis, anemia, hypersensitivity reactions.
 
Adults
Give by IV infusion over 1 hr; may switch to oralantibiotics after 3 days. =18yrs (CrCl >50mL/min): Intra-abdominal: 500mgevery 8 hrs for 5–14 days. UTI, pyelonephritis: 500mg every 8 hrs for 10–14days. CrCl 30–50mL/min: 250mg every 8 hrs; CrCl>10–<30mL/min: 250mg every12 hrs.
 
Children
<18yrs: not recommended.
 
Contraindications
Beta-lactam allergy.
 
Precautions
Pregnancy (Cat.B). Nursing mothers.
 
Interactions
Antagonizes valproic acid (monitor valproate frequently).Potentiated by probenecid (not recommended).