Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Doribax: 250 mg (1 ea [DSC]); 500 mg (1 ea [DSC])
Generic: 250 mg (1 ea [DSC]); 500 mg (1 ea [DSC])
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Distribution
Penetrates well into body fluids and tissues, including peritoneal and retroperitoneal fluids, gallbladder, bile, and urine; Vd: 16.8 L
Metabolism
Non-CYP-mediated metabolism via hydrolysis by dehydropeptidase-I to doripenem-M1 (inactive metabolite)
Excretion
Urine (71% as unchanged drug; 15% as doripenem-M1 metabolite); feces (<1%)
Half-Life Elimination
~1 hour
Protein Binding
~8.1%
Use in Specific Populations
Special Populations: Renal Function Impairment
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.
Use: Labeled Indications
Intra-abdominal infections, 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 infections, complicated (including pyelonephritis): Treatment of complicated urinary tract infections (UTIs), including pyelonephritis, caused by E. coli (including cases with concurrent bacteremia), Acinetobacter baumannii, K. pneumoniae, Proteus mirabilis, and P. aeruginosa.
Use: Off Label
Catheter-related bloodstream infectionsyes
Doripenem is recommended by IDSA clinical practice guidelines for the management of catheter-related bloodstream infections as a first-line agent for the treatment of catheter-related infections caused by ESBL-producing E. coli and Klebsiella species in adults. The guidelines also list doripenem as an appropriate alternative agent given with an aminoglycoside for catheter-related infections caused by O. anthropi. Doripenem may also be used in the treatment of catheter-related infections caused by susceptible Enterobacter species, S. marcescens, Acinetobacter species, P. aeruginosa, and B. cepacia.
Osteomyelitis, native vertebralyes
Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, doripenem is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to Pseudomonas aeruginosa.
Contraindications
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
Dosage and Administration
Dosing: Adult
Note: A switch to appropriate oral antimicrobial therapy may be considered after 3 days of parenteral therapy and demonstrated clinical improvement.
Intra-abdominal infection, complicated: IV: 500 mg every 8 hours for 5 to 14 days. Note: IDSA guidelines recommend treatment duration of 4 to 7 days (provided source controlled). Not recommended for mild to moderate, community-acquired intra-abdominal infections (Solomkin 2010).
Intravenous catheter-related bloodstream infection (off-label use): IV: 500 mg every 8 hours for 7 to 14 days (IDSA 2009)
Urinary tract infection, complicated (including pyelonephritis): IV: 500 mg every 8 hours for 10 to 14 days; when used for empiric therapy, use alone or in combination with other appropriate agents. Note: Reserved for critically ill patients or patients with risk factor(s) for multidrug-resistant (MDR) pathogens, including extended-spectrum beta-lactamase (ESBL)-producing organisms (Hooton 2018).
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Reconstitute 250 mg and 500 mg vial with 10 mL of SWFI or NS; further dilute the 250 mg vial for infusion with 50 mL or 100 mL of NS or D5W. Further dilute the 500 mg vials for infusion with 100 mL of NS or D5W. Shake gently until clear. To prepare a 250 mg dose using a 500 mg vial, reconstitute the 500 mg vial and further dilute with 100 mL of NS or D5W as above: remove and discard 55 mL from the infusion bag (remaining solution contains 250 mg) Variations in color when reconstituted or diluted from colorless to slightly yellow do not affect product potency.
Administration
IV: Infuse over 1 hour.
Storage
Store intact vials at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Reconstituted vial may be stored for up to 1 hour prior to preparation of infusion solution. Stability of solution when diluted in NS is 12 hours at room temperature or 72 hours at 2°C to 8°C (36°F to 46°F); stability in D5W is 4 hours at room temperature and 24 hours at 2°C to 8°C (36°F to 46°F). Do not freeze.
Drug Interactions
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. 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. 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. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. 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. Consider therapy modification
Adverse Reactions
>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 (formerly Clostridium) 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
Warnings/Precautions
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).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Appropriate use: Administer via intravenous infusion only. Per manufacturer’s labeling, investigational experience of doripenem via inhalation resulted in pneumonitis.
Monitoring Parameters
Monitor for signs of anaphylaxis during first dose; periodic renal assessment
Pregnancy
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies. Information related to use during pregnancy has not been located.
Patient Education
What is this drug used for?
- It is used to treat bacterial infections.
Frequently reported side effects of this drug
- Headache
- Nausea
- Diarrhea
- Injection site irritation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe loss of strength and energy
- Seizures
- Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools (rare)
- Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
