Note: Doribax injection (brand and generic) has been discontinued in the United States for >1 year.
Intra-abdominal infection, complicated: IV: 500 mg every 8 hours. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): IV: 500 mg every 8 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal function estimated using the Cockcroft-Gault formula:
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 50 mL/minute: 250 mg every 8 hours
CrCl 11 to 29 mL/minute: 250 mg every 12 hours
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Dialyzable (~52% of dose removed during 4-hour session in ESRD patients): 250 mg every 24 hours; if treating infections caused by Pseudomonas aeruginosa, administer 500 mg every 12 hours on day 1, followed by 500 mg every 24 hours (Tanoue 2011)
Peritoneal dialysis (PD): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
CVVHD: 1,000 mg every 8 hours (Vossen 2016)
CVVHDF: 250 mg every 12 hours (Hidaka 2010)
There are no dosage adjustments provided in manufacturer’s labeling (has not been studied); however, doripenem undergoes minimal hepatic metabolism.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Generic: 250 mg (1 ea [DSC]); 500 mg (1 ea [DSC])
Yes
Doribax injection (brand and generic) has been discontinued in the United States for >1 year.
IV: Infuse over 1 hour.
Intra-abdominal infection, complicated: Treatment of complicated intra-abdominal infections caused by Bacteroides caccae, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, Peptostreptococcus micros, Pseudomonas aeruginosa, Streptococcus intermedius, and Streptococcus constellatus.
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Treatment of complicated urinary tract infection, including pyelonephritis, caused by E. coli (including cases with concurrent bacteremia), Acinetobacter baumannii, K. pneumoniae, Proteus mirabilis, and P. aeruginosa.
Doripenem may be confused with ertapenem
Doribax may be confused with Zovirax
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (3% to 16%)
Gastrointestinal: Diarrhea (6% to 12%), nausea (4% to 12%)
1% to 10%:
Cardiovascular: Phlebitis (2% to 8%)
Dermatologic: Skin rash (1% to 6%; includes allergic/bullous dermatitis, erythema, macular/papular eruptions, urticaria, and erythema multiforme), pruritus (1% to 3%)
Gastrointestinal: Oral candidiasis (1% to 3%), Clostridioides difficile-associated diarrhea (≤1%)
Genitourinary: Vaginal infection (1% to 2%)
Hematologic & oncologic: Anemia (2% to 10%)
Hepatic: Increased serum transaminases (2% to 7%)
<1%, postmarketing, and/or case reports: Anaphylaxis, interstitial pneumonitis, leukopenia, neutropenia, renal failure, renal insufficiency, seizure, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis
Known serious hypersensitivity to doripenem, any component of the formulation or other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, and skin reactions have been reported in patients receiving beta-lactams.
• CNS effects: Carbapenems have been associated with CNS adverse effects, including confusional states; seizures with doripenem have been reported. Use caution with CNS disorders (eg, brain lesions, stroke, or history of seizures) and adjust dose in renal impairment to avoid drug accumulation, which may increase seizure risk. Patients receiving doses >500 mg every 8 hours may also be at increased risk of seizures.
• Superinfection: Use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in patients with moderate-to-severe renal dysfunction.
• Ventilator-associated pneumonia: Not approved for the treatment of pneumonia including hospital-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP). Demonstrated numerically lower cure rate (versus a comparator antibiotic) and increased mortality rate in patients with VAP in a Phase 3 study using a higher dose and fixed 7-day administration (Kollef 2012).
Other warnings/precautions:
• Appropriate use: Administer via intravenous infusion only. Per manufacturer’s labeling, investigational experience of doripenem via inhalation resulted in pneumonitis.
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Doripenem. This effect is due to probenecid's ability to decrease the active tubular secretion of doripenem. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Valproate Products: Carbapenems may decrease the serum concentration of Valproate Products. Management: Concurrent use of carbapenem antibiotics with valproic acid is generally not recommended. Alternative antimicrobial agents should be considered, but if a concurrent carbapenem is necessary, consider additional anti-seizure medication. Risk D: Consider therapy modification
Adverse events have not been observed in animal reproduction studies. Information related to use during pregnancy has not been located.
It is not known if doripenem is excreted into breast milk. The manufacturer recommends that caution be exercised when administering doripenem to nursing women.
Monitor for signs of anaphylaxis during first dose; periodic renal assessment
Inhibits bacterial cell wall synthesis by binding to several of the penicillin-binding proteins (PBP-2, PBP-3, PBP-4), which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis; bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Distribution: Penetrates well into body fluids and tissues, including peritoneal and retroperitoneal fluids, gallbladder, bile, and urine
Vd: 16.8 L
Protein binding: ~8.1%
Metabolism: Non-CYP-mediated metabolism via hydrolysis by dehydropeptidase-I to doripenem-M1 (inactive metabolite)
Half-life elimination: ~1 hour
Excretion: Urine (71% as unchanged drug; 15% as doripenem-M1 metabolite); feces (<1%)
Altered kidney function: Following a single 500 mg dose, the mean AUC in subjects with mild, moderate, and severe renal impairment was 1.6, 2.8, and 5.1 times that of age-matched healthy subjects with healthy renal function (CrCl 80 mL/minute or more), respectively.
Solution (reconstituted) (Doripenem Intravenous)
500 mg (per): $45.08
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