Doribax- New antibiotic treats abdominal infections

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Company:

Ortho-McNeil

Pharmacologic class:

Antibiotic (carbapenem)

Active ingredient:

Doripenem (as monohydrate) 500 mg/vial; powder; for IV infusion after constitution and dilution; preservative-free.

Indications:

Susceptible complicated intra-abdominal and complicated UTIs (including pyelonephritis).

Pharmacology:

Doripenem is a carbapenem antibiotic that has shown to be active against aerobic and anaerobic gram-negative and gram-positive bacteria. It inactivates multiple essential penicillin-binding proteins resulting in the inhibition of cell-wall synthesis with subsequent cell death.

It is stable to hydrolysis by most beta-lactamases produced by gram-negative and gram-positive 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, some bacterial isolates that are resistant to other carbapenems may be susceptible to doripenem.

Clinical trials:

A pair of double-blind studies involving 946 adults with complicated intra-abdominal infections (e.g., appendicitis, bowel perforation, cholecystitis, intra-abdominal or solid- organ abscess, peritonitis) were conducted to compare doripenem and meropenem. Both regimens allowed the option to switch to oral amoxicillin/clavulanate after three days of IV therapy with the study drugs for a total of 5-14 days of IV and oral treatment.

Doripenem was shown to be noninferior to meropenem in regard to clinical cure rates in patients with susceptible pathogens isolated at baseline and no major protocol deviations at test-of-cure visit 25-45 days after completion of therapy. It was also noninferior to meropenem in patients with baseline pathogens isolated regardless of susceptibility.

Two multicenter, randomized studies compared doripenem to levofloxacin in 1,171 adults with complicated UTIs. One was a double-blind study, and the other was a noncomparative study. Both allowed the option of switching to oral levofloxacin after at least three days of IV therapy for a total of 10 days of treatment. Patients with bacteremia were allowed to receive levofloxacin for a total of 10-14 days.

Doripenem was shown to be noninferior to levofloxacin with regard to microbiologic eradication rates in patients with baseline pathogens, no major protocol deviations, and urine cultures at the test-of-cure visit 5-11 days after completing therapy. It was also noninferior in patients with pretreatment urine cultures.

Adults:

Give by IV infusion over one hour; may switch to oral antibiotics after three days. ≥18 years (CrCl >50 mL/min): Intraabdominal: 500 mg every eight hours for 5-14 days. UTI, pyelonephritis: 500 mg every eight hours for 10-14 days. CrCl 30-50 mL/min: 250 mg every eight hours; CrCl>10-<30 mL/min: 250 mg every 12 hours.

Children:

<18 years: not recommended.

Contraindications:

Beta-lactam allergy.

Precautions:

Pregnancy (Cat. B). Nursing mothers.

Interactions:

Antagonizes valproic acid (monitor valproate frequently). Potentiated by probenecid (not recommended).

Adverse reactions:

Headache, nausea, diarrhea (may be serious; evaluate if occurs), rash, phlebitis, anemia, hypersensitivity reactions.

How supplied:

Single-use vials—10

For more information, call 800.526.7736 or visit www.Doribax.com

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