Doripenem

Indications

Doripenem is used for: Intra-abdominal infections, Bacterial infections, Septicemia, Nosocomial pneumonia, Urinary tract infections, Pyelonephritis

Adult Dose

Intravenous Complicated intra-abdominal infections Adult: 500 mg 8 hrly infused over 1 hr for 5-14 days. May switch to an appropriate oral therapy, after at least 3 days of parenteral therapy upon evidence of clinical improvement. Complicated urinary tract infections; Pyelonephritis Adult: 500 mg 8 hrly infused over 1 hr for 10 days. May switch to an appropriate oral therapy, after at least 3 days of parenteral therapy upon evidence of clinical improvement. Duration can be extended up to 14 days for patients w/ concurrent bacteraemia.

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment: CrCl (ml/min) 30-50 250 mg every 8 hr by IV infusion over 1 hr 11-29 250 mg every 12 hr by IV infusion over 1 hr

Administration

Reconstitution: 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 For a 250 mg dose, contents of the reconstituted vial should be withdrawn and added to 100 mL NaCl 0.9% infusion bag or dextrose 5% inj.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. IV Administration Infuse over 1 hr

Contra Indications

Hypersensitivity; anaphylactic reactions to beta-lactams.

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. Lactation: unknown if excreted in breast milk; use caution

Pregnancy-Lactation

Pregnancy Category: B Lactation: unknown if excreted in breast milk; use caution

Interactions

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

Adverse Effects

Side effects of Doripenem : >10% Headache (4-16%), Nausea (4-12%), Diarrhea (6-11%) 1-10% Anemia (2-10%), Phlebitis (4-8%), Rash (1-5%), Pruritus (3%), Transaminases elevated (1-2%), Oral candidiasis (1%), Renal impairment/failure (1%) Potentially Fatal: Anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson Syndrome, interstitial pneumonia, seizure.

Mechanism of Action

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.