Doripenem

Indications
 Intravenous
Complicated intra-abdominal infections
Adult: ≥18 yr: 500 mg every 8 hr by IV infusion over 1 hr. Treatment duration is 5-14 days; may switch to an appropriate oral therapy, after at least 3 days of parenteral therapy upon evidence of clinical improvement.
CrCl (ml/min)Dosage Recommendation
30-50250 mg every 8 hr by IV infusion over 1 hr
11-29250 mg every 12 hr by IV infusion

Intravenous
Complicated urinary tract infections
Adult: ≥18 yr: 500 mg every 8 hr by IV infusion over 1 hr. Treatment duration is 10 days, and can be extended up to 14 days for patients with concurrent bacteraemia.
CrCl (ml/min)Dosage Recommendation
30-50250 mg every 8 hr by IV infusion over 1 hr
11-29250 mg every 12 hr by IV infusion over 1 hr

Intravenous
Pyelonephritis
Adult: ≥18 yr: 500 mg every 8 hr by IV infusion over 1 hr. Treatment duration is 10 days, and can be extended up to 14 days for patients with concurrent bacteraemia.
CrCl (ml/min)Dosage Recommendation
30-50250 mg every 8 hr by IV infusion over 1 hr
11-29250 mg every 12 hr by IV infusion over 1 hr

Intravenous
Nosocomial pneumonia
Adult: ≥18 yr: 500 mg every 8 hr by IV infusion over 1 or 4 hr (Infections with less susceptible pathogens may use 4-hr infusion).

Reconstitution: Reconstitute the 500 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension with resultant concentration of 50 mg/mL. Further dilute the reconstituted vial with 100 mL of normal saline or 5% dextrose; gently shake until clear. The concentration of final infusion solution: 4.5 mg/mL. For 250 mg dose: Reconstitute 500 mg vial with 10 mL of sterile water for injection or normal saline, further dilute with 100 mL of compatible solution as above. Remove and discard 55mL from the infusion bag to leave the remaining solution
Contraindications
 Hypersensitivity; anaphylactic reactions to beta-lactams.
Warnings / Precautions
 May decrease serum concentration of valproic acid to below therapeutic range thus increasing risk of breakthrough seizure; consider alternative antimicrobial agents or additional anti-seizure medications if concurrent usage is necessary. Prolonged use may result in Clostridium difficile-associated diarrhoea (CDAD). May cause development of drug-resistant bacteria when used in the absence of proven or strongly suspected bacterial infection. Renal impairment. Safety and efficacy have not been established in patients <18 yr old.
Adverse Reactions
 Headache, nausea, diarrhoea, rash, phlebitis, elevated hepatic enzymes, oral candidiasis, anaemia, vulvomycotic infection, renal impairment, neutropenia, leucopenia, thrombocytopenia.
Potentially Fatal: Anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson Syndrome, interstitial pneumonia, seizure.
Drug Interactions
 May decrease valproic acid serum concentrations. Probenecid may increase serum levels of doripenem and concomitant use is not recommended.
See Below for More doripenem Drug Interactions
Mechanism of Actions
 Doripenem is a broad-spectrum carbapenem with potent in vitro antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria including Pseudomonas aeruginosa. It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins; which in turn inhibits the final transpeptidase step of peptidoglycan synthesis in bacterial cell walls.
Absorption: Cmax<109>) and AUC are linear over a dose range of 0.5-1 g when given over 1 hr by IV infusion.
Distribution: Average binding to plasma proteins: About 8.1%; independent of plasma drug concentrations. Median V<209>d: 16.8 L
Metabolism: Primarily metabolised by dehydropeptidase-I to a microbiologically inactive ring-opened metabolite.
Excretion: Primarily excreted in urine (about 70% as unchanged drug, about 15% as ring-opened metabolite); faeces (≤1%). Mean half-life elimination in healthy adults: About 1 hr.
Storage Conditions
 Intravenous: Reconstituted suspension may be held for 1 hr prior to dilution in infusion bag. Following dilution of the suspension with normal saline, stability is 12 hr at room temperature or 72 hr under refrigeration. Stability of solution when diluted with Dextrose 5% is 4 hr at room temperature and 24 hr under refrigeration.
ATC Classification
 J01DH04 - doripenem ; Belongs to the class of carbapenems. Used in the systemic treatment of infections.
Storage
 Intravenous: Reconstituted suspension may be held for 1 hr prior to dilution in infusion bag. Following dilution of the suspension with normal saline, stability is 12 hr at room temperature or 72 hr under refrigeration. Stability of solution when diluted with Dextrose 5% is 4 hr at room temperature and 24 hr under refrigeration.
Available As
  • Doripenem 500 mg

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