Doripenem

Intravenous
Complicated intra-abdominal infections
Adult: 500 mg 8 hourly via IV infusion over 1 hour for 5-14 days. May switch to an appropriate oral treatment, after at least 3 days of parenteral therapy, once clinical improvement has been achieved.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
11-29	250 mg 12 hourly.
30-50	250 mg 8 hourly.

Reconstitution: Reconstitute a 250 mg and 500 mg vial with 10 mL of sterile water for inj or NaCl 0.9% inj to form a suspension containing 25 mg/mL and 50 mg/mL concentration, respectively. Further dilute the reconstituted 250 mg vial with 50 mL or 100 mL of NaCl 0.9% inj or dextrose 5% in water to a final concentration of approx 4.2 mg/mL (50 mL infusion bag) or approx 2.3 mg/mL (100 mL infusion bag). Further dilute the reconstituted 500 mg vial with 100 mL of NaCl 0.9% inj or dextrose 5% in water to a final concentration of 4.5 mg/mL. Gently shake until clear. To prepare a 250 mg dose using a 500 mg vial, reconstitute and further dilute the 500 mg vial with NaCl 0.9% solution or dextrose 5% in water as above. Thereafter, remove and discard 55 mL from the infusion bag to leave the remaining solution containing 250 mg.

Intravenous
Pyelonephritis
Adult: 500 mg 8 hourly via IV infusion over 1 hour for 10 days. May switch to an appropriate oral treatment, after at least 3 days of parenteral therapy, once clinical improvement has been achieved. In patients with concurrent bacteraemia, treatment duration can be extended up to 14 days.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
11-29	250 mg 12 hourly.
30-50	250 mg 8 hourly.

Reconstitution: Reconstitute a 250 mg and 500 mg vial with 10 mL of sterile water for inj or NaCl 0.9% inj to form a suspension containing 25 mg/mL and 50 mg/mL concentration, respectively. Further dilute the reconstituted 250 mg vial with 50 mL or 100 mL of NaCl 0.9% inj or dextrose 5% in water to a final concentration of approx 4.2 mg/mL (50 mL infusion bag) or approx 2.3 mg/mL (100 mL infusion bag). Further dilute the reconstituted 500 mg vial with 100 mL of NaCl 0.9% inj or dextrose 5% in water to a final concentration of 4.5 mg/mL. Gently shake until clear. To prepare a 250 mg dose using a 500 mg vial, reconstitute and further dilute the 500 mg vial with NaCl 0.9% solution or dextrose 5% in water as above. Thereafter, remove and discard 55 mL from the infusion bag to leave the remaining solution containing 250 mg.

Intravenous
Complicated urinary tract infections
Adult: 500 mg 8 hourly via IV infusion over 1 hour for 10 days. May switch to an appropriate oral treatment, after at least 3 days of parenteral therapy, once clinical improvement has been achieved. In patients with concurrent bacteraemia, treatment duration can be extended up to 14 days.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
11-29	250 mg 12 hourly.
30-50	250 mg 8 hourly.

Reconstitution: Reconstitute a 250 mg and 500 mg vial with 10 mL of sterile water for inj or NaCl 0.9% inj to form a suspension containing 25 mg/mL and 50 mg/mL concentration, respectively. Further dilute the reconstituted 250 mg vial with 50 mL or 100 mL of NaCl 0.9% inj or dextrose 5% in water to a final concentration of approx 4.2 mg/mL (50 mL infusion bag) or approx 2.3 mg/mL (100 mL infusion bag). Further dilute the reconstituted 500 mg vial with 100 mL of NaCl 0.9% inj or dextrose 5% in water to a final concentration of 4.5 mg/mL. Gently shake until clear. To prepare a 250 mg dose using a 500 mg vial, reconstitute and further dilute the 500 mg vial with NaCl 0.9% solution or dextrose 5% in water as above. Thereafter, remove and discard 55 mL from the infusion bag to leave the remaining solution containing 250 mg.

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

Patient with CNS disorders (e.g. brain lesions, history of seizures). Renal impairment. Elderly. Pregnancy and lactation. Monitoring Parameters Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor renal function (e.g. serum creatinine, BUN) and for signs of anaphylaxis during 1st dose. Check for severe or bloody diarrhoea.

Significant: CNS effects (e.g. confusional states, seizures). Blood and lymphatic system disorders: Anaemia. Rarely, thrombocytopenia, neutropenia. Gastrointestinal disorders: Nausea, diarrhoea. Infections and infestations: Oral candidiasis, vaginal infection. Investigations: Increased serum transaminases. Nervous system disorders: Headache. Renal and urinary disorders: Renal impairment or failure. Skin and subcutaneous tissue disorders: Skin rash, pruritus.
Potentially Fatal: Serious hypersensitivity reactions (e.g. anaphylaxis, serious skin reactions); Clostridioides difficile-associated diarrhoea (CDAD) and pseudomembranous colitis.

Probenecid interferes with active tubular secretion of doripenem which results in increased doripenem plasma levels. May decrease the serum concentrations of valproic acid to subtherapeutic levels.

Doripenem is a synthetic broad-spectrum carbapenem β-lactam antibiotic. It binds to several penicillin-binding proteins (PBP-2, PBP-3, PBP-4), which blocks the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thereby inhibiting bacterial cell wall biosynthesis and eventually resulting in cell death.
Distribution: Penetrates well into body tissues and fluids, including gallbladder, bile, urine, and peritoneal and retroperitoneal fluids. Volume of distribution: 16.8 L. Plasma protein binding: Approx 8.1%.
Metabolism: Metabolised via hydrolysis primarily by dehydropeptidase I to form doripenem-M1 (inactive metabolite).
Excretion: Mainly via urine (71% as unchanged drug, 15% as metabolite); faeces (<1%). Elimination half-life: Approx 1 hour.

Intravenous: Intact vial: Store between 15-30°C. Reconstituted suspension may be stored for up to 1 hour before dilution in the infusion bag. Diluted infusion solution (prepared with NaCl 0.9% inj): Stable for 12 hours at room temperature and 72 hours between 2-8°C. Diluted infusion solution (prepared with dextrose 5% in water): Stable for 4 hours at room temperature and 24 hours between 2-8°C. Do not freeze.

Other Beta-Lactams

J01DH04 - doripenem ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.