Doripenem
Common Brand Names: Doribax
Therapeutic Class: Semisynthetic carbapenem antimicrobial agent.
Common Injectable Dosage Forms:
Powder for Reconstitution: 500 mg vials
Dosage Ranges:
Indicated in treatment of intra-abdominal infections and urinary tract infections including pyelonephritis: 500 mg every 8 hours for 5-14 days.
Dose in renal impairment (CrCl <50 mL/min): 250 mg every 8-12 hours.
Administration and Stability: Does not contain bacteriostatic preservative. Reconstitute vials with 10 mL Sterile Water for Injection, or sodium chloride 0.9% for a concentration of 50 mg/mL. Further dilute by adding 100 mL NS or D5W for a final concentration of 4.5 mg/mL. Admixture is stable for 8 hours in NS and 4 hours in D5W at room temperature or 24 hours under refrigeration. Do not freeze. Administer by intravenous route over 1 hour.
Pharmacology/Pharmacokinetics: Doripenem is a semisynthetic carbapenem which inhibits cell wall formation, facilitates bacterial cell lysis, and is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by binding to specific penicillin-binding proteins located inside the cell wall. Mean peak plasma concentrations after a 500 mg single dose is approximately 23 mcg/mL. Doripenem is distributed into most body fluids and tissues, including bile, gallbladder, peritoneal exudate, and urine. Plasma protein binding is approximately 8.1%. Hepatic enzymes are not involved in the metabolism of doripenem. It is excreted mostly unchanged in urine with 70% of the dose recovered over 48 hours. Elimination half-life is around 1 hour.
Drug and Lab Interactions: Carbapenems can reduce serum concentration of valproic acid to subtherapeutic levels when the two are coadministered. Probenecid inhibits the renal excretion of doripenem, increasing its elimination half-life by 53% and AUC to 75%.
Contraindications/Precautions: Contraindicated in patients with known hypersensitivity to doripenem, cephalosporins, penicillins, or any beta-lactam antibiotic. Use with caution in patients who have colitis, diarrhea, GI disease, renal impairment, seizure disorder, are breastfeeding, and in the elderly. Pregnancy Category B.
Monitoring Parameters: Cr, BUN
Adverse Effects: Most commonly reported adverse effects are headache and rash. Other reported adverse reactions include nausea, diarrhea, anemia, renal failure, elevated LFTs, and oral candidiasis. Some instances of Stevens-Johnson syndrome, interstitial pneumonia, and toxic epidermal necrolysis have been reported.
Common Clinical Applications: Doripenem had good activity against both gram-positive and gram-negative bacteria. It appears to have superior in vitro activity against Pseudomonas aeruginosa compared to imipenem and meropenem. It is stable against most beta-lactamases and it effective at low doses.
