Doripenem

Intravenous
Complicated intra-abdominal infections

Intravenous
Complicated urinary tract infections, Pyelonephritis

CrCl	Dosage
11-29	250 mg 12 hrly.
30-50	250 mg 8 hrly.

Reconstitute 500 mg vial w/ 10 mL of sterile water for inj or NaCl 0.9% inj to form a susp containing 50 mg/mL. Further dilute the reconstituted vial w/ 100 mL of NaCl 0.9% or dextrose 5% inj, gently shake until clear. For a 250 mg dose, contents of the reconstituted vial should be withdrawn and added to 100 mL NaCl 0.9% infusion bag or dextrose 5% inj. Remove and discard 55 mL from the infusion bag to leave the remaining soln.

Diazepam, K phosphates, propofol.

Hypersensitivity to doripenem, other carbapenem antibacterial agents; history of anaphylactic reaction to β-lactams (e.g. penicillins, cephalosporins).

Patient w/ known or suspected CNS disorders (e.g. brain lesions, history of seizures). Not intended for treatment of any type of pneumonia. Renal impairment. Pregnancy and lactation.

Headache, nausea, diarrhoea, rash, pruritus, phlebitis, elevated hepatic enzymes, oral candidiasis, anaemia, vulvomycotic infection, thrombocytopenia, neutropenia.
Potentially Fatal: Hypersensitivity reactions (e.g. anaphylaxis), Clostridium difficile-associated colitis.

IV/Parenteral: B

Monitor renal function and for signs of anaphylaxis during 1st dose. Consider haematologic assessment during prolonged therapy.

Increased plasma concentration w/ probenecid. May decrease plasma levels of valproic acid thus, increasing the risk of seizures.

Description: Doripenem is a synthetic broad-spectrum carbapenem β-lactam antibiotic w/ potent in vitro antibacterial activity against aerobic and anaerobic gm+ve and gm-ve bacteria including Pseudomonas aeruginosa. It inhibits bacterial cell wall synthesis by binding to several penicillin-binding proteins, which in turn inhibits the final transpeptidase step of peptidoglycan synthesis in bacterial cell walls.
Pharmacokinetics:
Distribution: Widely distributed into body tissues and fluids. Volume of distribution: 16.8 L. Plasma protein binding: <10%.
Metabolism: Primarily metabolised via hydrolysis of its β-lactam ring by dehydropeptidase I to a microbiologically inactive open-ringed metabolite (doripenem-M1).
Excretion: Mainly excreted in the urine by tubular secretion and glomerular filtration (approx 70% as unchanged drug, approx 15% as metabolite); faeces (<1%). Elimination half-life: Approx 1 hr.

Reconstituted susp may be held for 1 hr prior to dilution in infusion bag. Following dilution of the susp w/ NaCl 0.9%, stability is 8 hr at room temperature or 24 hr between 2-8°C. Stability of soln when diluted w/ dextrose 5% inj is 4 hr at room temperature or 24 hr between 2-8°C.

Other Beta-Lactams

Anon. Doripenem. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/05/2014.

Buckingham R (ed). Doripenem. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com . Accessed 05/05/2014.

Doribax Powder, for Solution (Shionogi Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/05/2014.

Label Changes for Antibacterial Doribax (doripenem) Describing Increased Risk of Death for Ventilator Patients with Pneumonia. U.S. FDA. https://www.fda.gov/. Accessed 05/05/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Doripenem. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/05/2014.