Dosing and uses of Doribax (doripenem)
Adult dosage forms and strengths
powder for injection
- 500mg/vial
Complicated Intra-abdominal Infection
500 mg IV infusion over 1 hour q8hr x 5-14 days
At least 3 days IV, may switch to an appropriate PO treatment if clinical improvement noted
Complicated UTI
500 mg IV infusion over 1 hour q8hr x 10 days
Can be extended up to 14 days if concurrent bacteremia
Bronchopulmonary Infection (Orphan)
Treatment of bronchopulmonary infection in patients with cystic fibrosis who are colonized with Pseudomonas aeruginosa or Burkholderia cepacia
Orphan indication sponsor
- Johnson & Johnson Pharmaceutical, Research & Dev; 920 US Highway 202, P. O. Box 300; Raritan, NJ 08869
Renal Impairment
CrCl >50 mL/min: No adjustment
CrCl 30-50 mL/min: 250 mg IV q8hr
CrCl 10-30 mL/min: 250 mg IV q12hr
Other Indications & Uses
P. aeruginosa, K. pneumoniae, E. coli, Bacteroides caccae, B. fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, Streptococcus intermedius, S. constellatus, Peptostreptococcus micros, Acinetobacter baumannii, Proteus mirabilis
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Doribax (doripenem) adverse (side) effects
>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%)
Postmarketing Reports
Anaphylaxis
Leukopenia
Neutropenia
Seizure
Thrombocytopenia
Toxic epidermal necrolysis, Stevens-Johnson Syndrome
Interstitial pneumonia
Renal impairment/failure
Warnings
Contraindications
Hypersensitivity to doripenem, beta-lactams or similar drugs
Cautions
History of sensitivity to multiple allergens
May reduce serum valproic acid conc to subtherapeutic level: monitor levels frequently
Risk of Clostridium difficile-associated diarrhea on long-term use
Seizures reported with use
Not approved for ventilator-associated bacterial pneumonia (or any type of pneumonia); increased mortality when compared with imipenem/cilastatin (23% vs 16.7%); additionally, clinical response rates were lower with doripenem
Pregnancy and lactation
Pregnancy category: B
Lactation: unknown if excreted in breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Doribax (doripenem)
Mechanism of action
Inhibits cell-wall biosynthesis by inactivating multiple penicillin-binding proteins (PBPs), resulting in cell death
Stable to hydrolysis by most beta-lactamases
Distribution
Penetrates into several body fluids and tissues, especially peritoneal and retroperitoneaL
Protein Bound: 8.1%
Vd: 16.8 L
Metabolism
Dehydropeptidase-I
Elimination
Half-life: 1 hr (normal renal function)
Plasma Clearance: 15.9 L/hr
Excretion: urine
Administration
IV Preparation
Reconstitute vial with 10 mL SWI or NS; shake gently to form suspension
- Add to infusion bag containing 100 mL NS or D5W
- Shake gently until clear
To prepare 250 mg infusion soln for pts w/ renal impairment
- Remove 55 mL of soln from bag & discard
- Infuse remaining soln
IV Administration
Infuse over 1 hr
Storage
Store vials at 25°C (77°F)
Constituted Doribax suspension in vial may be held for 1 hr prior to transfer & dilution in infusion bag
Diluted suspension (already in infusion bag) in NS may be stored for 8 hr and in D5W for 4 hr at room temp (includes storage & infusion time) OR in either diluent for 24 hr at 2-8°C (includes storage & infusion time)
