doripenem
Brand: Doribax
Prototype: imipenem-cilastatin
Drug Class: carbapenem antibiotic
Drug Family: antibiotic
Subclass: anti-pseudomonal carbapenem
Organ Systems: infectious-disease
Mechanism of Action
Inhibits bacterial cell wall synthesis; similar spectrum to meropenem with activity against Pseudomonas aeruginosa; slightly lower seizure potential than imipenem.
penicillin-binding proteins (PBPs)
Indications
- complicated UTI including pyelonephritis
- complicated intra-abdominal infections
- hospital-acquired pneumonia (off-label in some regions)
Contraindications
- carbapenem/beta-lactam hypersensitivity
Adverse Effects
Common
- diarrhea
- nausea
- headache
- injection site phlebitis
Serious
- C. difficile colitis
- anaphylaxis
- seizures
- pneumonitis (with inhalation — do not use inhaled)
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | widely distributed; moderate CSF penetration |
| Metabolism | minimal; hydrolysis to inactive ring-opened form |
| Excretion | renal (>70% unchanged) |
| Half-life | 1 hour |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | 8 hours |
| Protein Binding | 8% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| valproate | reduces valproate levels; seizure risk | major |
| probenecid | reduces renal excretion | minor |
Nursing Considerations
- Administer IV over 1 hour (60-minute infusion) or 4 hours (extended infusion for severe Pseudomonas infections).
- Monitor for C. difficile infection; doripenem has broad-spectrum activity that disrupts normal flora.
- Adjust dose in renal impairment; close monitoring required when CrCl falls below 30 mL/min.
- Avoid concurrent use with valproate; notify prescriber and monitor valproate levels if combination is unavoidable.
Clinical Pearls
- Extended infusion of doripenem (4-hour infusion) improves pharmacodynamic target attainment against Pseudomonas aeruginosa strains with higher MICs, a strategy increasingly used in the ICU.
- Doripenem was NOT FDA-approved for VAP in clinical trials (IDSA guidelines note non-inferiority data with imipenem/meropenem), so meropenem is generally preferred for HAP/VAP.
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.