Trade Names:Doribax- Injection, powder for solution, concentrate 500 mg
Inhibits bacterial cell wall biosynthesis, resulting in cell death.
Pharmacokinetics are linear over a dose range of 500 to 1,000 mg IV over 1 h. Following a single 1 h IV infusion of 500 mg, the mean plasma C max and AUC are 23 mcg/mL and 36.3 mcg•h/mL, respectively.
Average plasma protein binding is approximately 8%. Vd is 16.8 L. Doripenem penetrates into several body fluids and tissues, including those at the site of infection for approved indications.
Metabolized to an inactive ring-opened metabolite by dehydropeptidase-I. Doripenem is not a substrate for hepatic CYP-450 enzymes.
Terminal t ½ is approximately 1 h. Mean plasma Cl is 15.9 L/h, and mean renal Cl is 10.8 L/h. Within 48 h, approximately 70% is excreted unchanged by the kidneys and 15% as the ring-opened metabolite. Less than 1% excreted in feces after 1 wk.
Dosage adjustment is necessary in patients with moderate and severe renal function impairment.Hepatic Function Impairment
Not established; however, because doripenem does not undergo hepatic metabolism, the pharmacokinetics are not expected to be affected by hepatic function impairment.Elderly
No dosage adjustments are needed in elderly patients with healthy renal function.Gender
No dosage adjustments are recommended based on gender.Race
No dosage adjustments are recommended based on race.
As a single-agent for the treatment of complicated intra-abdominal infections and complicated UTIs, including pyelonephritis caused by susceptible strains of specific microorganisms. To reduce the development of drug-resistant bacteria and maintain effectiveness of doripenem and other antibacterial agents, use only to treat infections proven or strongly suspected to be caused by susceptible bacteria.
Known serious hypersensitivity to doripenem or other carbapenem antibiotics or demonstrated anaphylactic reactions to beta-lactams.
IV 500 mg, infused over 1 h, every 8 h for 5 to 14 days.Complicated UTI, Including PyelonephritisAdults
IV 500 mg, infused over 1 h, every 8 h for 10 days. Duration may be extended to 14 days for patients with concurrent bacteremia.Renal Function ImpairmentAdults
IV CrCl 30 to 50 mL/min or less: 250 mg, infused over 1 h, every 8 h; CrCl greater than 10 to less than 30 mL/min: 250 mg, infused over 1 h, every 12 h.
Store vial at 59° to 86°F. Constituted suspension in vial may be stored for 1 h prior to dilution in infusion bag. Infusion solution prepared in normal saline may be stored at room temperature for 8 h (includes infusion time) or under refrigeration for 24 h (includes infusion time). Infusion solution prepared in dextrose 5% may be stored at room temperature for 4 h (includes infusion time) or under refrigeration for 24 h (includes infusion time).
Doripenem plasma levels may be increased and prolonged because of interference with active tubular secretion by probenecid.Valproic acid
Valproic acid serum concentrations may be reduced to subtherapeutic levels, resulting in loss of seizure control. If serum valproic acid levels cannot be maintained in the therapeutic range or if seizures occur, consider alternative antibacterial or anticonvulsant therapy.
None well documented.
Headache (16%); seizures (postmarketing).
Rash, including allergic dermatitis (5%); pruritus (3%); Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).
Nausea (12%); diarrhea (11%); oral candidiasis (1%).
Vulvomycotic infection (2%); renal function impairment/renal failure (1%).
Elevated hepatic enzymes (2%).
Interstitial pneumonia (postmarketing).
Category B .
Safety and efficacy not established.
Because elderly patients are more likely to have decreased renal function or prerenal azotemia, select dose with care.
Serious and occasionally fatal anaphylactic and serious skin reactions have been reported in patients receiving beta-lactam antibiotics.
Dosage adjustment is needed in patients with moderate and severe renal function impairment.
May result in bacterial or fungal overgrowth of nonsusceptible organisms.
Consider possibility in patients with diarrhea.
Discontinue doripenem and administer supportive treatment.
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