doripenem (Doribax)

Introduction

Tradename: Doribax

Indications

• bacterial infections due to susceptible organisms
  • complicated urinary tract infection
  • pyelonephritis
    • intra-abdominal infections
      • appendicitis
      • cholecystitis
      • bacterial peritonitis
      • abdominal abscess
• FDA approval for hospital-acquired pneumonia sought

Contraindications

Pregnancy category: B

Dosage

• 500 mg IV every 8 hours, infused over 1 hour
• 500 mg vials for reconstitution

reconstitute in 20 mL of normal saline of sterile water

stable at room temperature for 8 hours & for 24 hours refrigerated

Dosage adjustment in renal failure

• 250 mg every 8 hours for creatinine clears 30-50 mL/min
• 250 mg every 12 hours for creatinine clears 11-30 mL/min

Antimicrobial activity

• broad spectrum, especially gram negative organisms
  • E coli
  • K pneumoniae
  • P mirabilis
  • P aeruginosa
  • B caccae
  • B fragilis
  • B thetaiotaomicron
  • B uniformis
  • B vulgatus
  • S intermedius
  • S contellatus
• Peptostreptococus micros

Adverse effects

• headache (16%)
• nausea (12%)
• diarrhea (11%)
• rash (5%)
• phlebitis (8%)
• lower risk for seizures than other carbapenems
• increased mortality compared with imipenem cilastatin when used to treat ventilator-associated pneumonia
• doripenem similar in efficacy & adverse events to other carbapenems

Drug interactions

• doripenem lowers valproic acid levels

• drug interaction(s) anticonvulsants with anti-bacterial agents
• drug interaction(s) of antibiotics with warfarin

Mechanism of action

• inhibits bacterial cell wall synthesis
• CNS penetration not well defined

More general terms

• carbapenem (thienamycin)