(dore i PEN em)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Doribax: 250 mg (1 ea); 500 mg (1 ea)
Brand Names: U.S.
- Antibiotic, Carbapenem
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.
Penetrates well into body fluids and tissues, including peritoneal and retroperitoneal fluids, gallbladder, bile, and urine; Vd: 16.8 L
Non-CYP-mediated metabolism via hydrolysis by dehydropeptidase-I to doripenem-M1 (inactive metabolite)
Urine (71% as unchanged drug; 15% as doripenem-M1 metabolite); feces (<1%); Dialyzable with reduction in systemic levels by 48% to 62%
8% to 9%
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
Treatment of complicated intra-abdominal infections and complicated urinary tract infections (including pyelonephritis) due to susceptible aerobic gram-positive, aerobic gram-negative (including Pseudomonas aeruginosa), and anaerobic bacteria
Treatment of intravascular catheter-related bloodstream infection due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp
Known serious hypersensitivity to doripenem or other carbapenems (eg, ertapenem, imipenem, meropenem) or any component of the formulation; anaphylactic reactions to beta-lactam antibiotics
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, severe: IV: 500 mg every 8 hours for 5 to 14 days. Note: 2010 IDSA guidelines recommend treatment duration of 4 to 7 days (provided source controlled). Not recommended for mild to moderate, community-acquired intra-abdominal infections due to risk of toxicity and the development of resistant organisms (Solomkin 2010).
Osteomyelitis, native vertebral (off-label use) (IDSA [Berbari 2015]): P. aeruginosa: IV: 500 mg every 8 hours for 6 weeks. Note: Double coverage may be considered (ie, doripenem plus an aminoglycoside or ciprofloxacin)
Urinary tract infection (complicated) or pyelonephritis: IV: 500 mg every 8 hours for 10 to 14 days
Intravenous catheter-related bloodstream infection (off-label use): IV: 500 mg every 8 hours for 7 to 14 days (IDSA, 2009)
Refer to adult dosing.
Dosing: Renal Impairment
CrCl >50 mL/minute: No adjustment necessary.
CrCl 30-50 mL/minute: 250 mg every 8 hours
CrCl 11-29 mL/minute: 250 mg every 12 hours
Hemodialysis: Dialyzable (~52% of dose removed during 4-hour session in ESRD patients)
Intermittent HD: 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)
CVVHDF: 250 mg every 12 hours (Hidaka, 2010).
Dosing: Hepatic Impairment
There are no dosage adjustments provided in manufacturer’s labeling (has not been studied). However, doripenem undergoes minimal hepatic metabolism.
Reconstitute 250 mg vial with 10 mL of SWFI or NS; further dilute for infusion with 50 mL or 100 mL of NS or D5W. Shake gently until clear. Reconstitute 500 mg vial with 10 mL of SWFI or NS; further dilute for infusion with 100 mL of NS or D5W. Shake gently until clear. Reconstituted vial may be stored for up to 1 hour prior to preparation of infusion solution. To prepare a 250 mg dose using a 500 mg vial, reconstitute the 500 mg vial with 10 mL of SWFI or NS and further dilute with 100 mL of compatible solution as above, but remove and discard 55 mL from the infusion bag to leave the remaining solution containing the 250 mg dose.
Infuse intravenously over 1 hour. Use of 4-hour infusion has been studied in the treatment of VAP (off-label use) (Chastre, 2008).
Stable in D5W, NS.
Y-site administration: Incompatible: with diazepam, potassium phosphates, propofol.
Store dry powder vials at 15°C to 30°C (59°F to 86°F). Stability of solution when diluted in NS is 12 hours at room temperature or 72 hours under refrigeration; stability in D5W is 4 hours at room temperature and 24 hours under refrigeration.
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. 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
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%), Clostridium dificile associated diarrhea (≤1%)
Genitourinary: Vaginal infection (1% to 2%)
Hematologic & oncologic: Anemia (2% to 10%)
Hepatic: Increased serum transaminases (2% to 7%)
<1% (Limited to important or life-threatening): Anaphylaxis, interstitial pneumonitis, leukopenia, neutropenia, renal failure, renal insufficiency, seizure, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis
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 and seizures (myoclonic); 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.
• 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 healthcare-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.
• Appropriate use: Administer via intravenous infusion only. Per manufacturer’s labeling, investigational experience of doripenem via inhalation resulted in pneumonitis.
Monitor for signs of anaphylaxis during first dose; periodic renal assessment; consider hematologic monitoring during prolonged therapy
Pregnancy Risk Factor
Adverse events have not been observed in animal reproduction studies. Information related to use during pregnancy has not been located.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, nausea, diarrhea, or injection site irritation. Have patient report immediately to prescriber confusion, severe loss of strength and energy, seizures, vaginitis, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about doripenem
- Other brands: Doribax