Doribax

doripenem monohydrate

Doribax

Pharmacologic class: Carbapenem

Therapeutic class: Anti-infective

Pregnancy risk category B

GI: nausea, diarrhea, oral candidiasis, Clostridium difficile-associated diarrhea

Action

Acts against aerobic and anaerobic gram-positive and gram-negative bacteria

Availability

Powder for reconstitution for infusion: 500 mg single-use vials

Indications and dosages

Complicated intra-abdominal infections caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides caccae, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Streptococcus intermedius, Streptococcus constellatus, and Peptostreptococcus micros; complicated urinary tract infections (UTIs), such as pyelonephritis caused by E. coli (including cases with concurrent bacteremia), K. pneumoniae, Proteus mirabilis, P. aeruginosa, and Acinetobacter baumannii

Adults ages 18 and older: 500 mg q 8 hours by I.V. infusion over 1 hour; continue for 5 to 14 days for complicated intra-abdominal infections and 10 days for complicated UTIs, with possible extension to 14 days for patients with concurrent bacteremia

Dosage adjustment

• Renal impairment

Contraindications

• Serious hypersensitivity to drug or other carbapenems
• History of anaphylactic reactions to beta-lactams

Precautions

Use cautiously in:
• renal impairment
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

Don't use constituted suspension for direct injection; dilute further before giving by I.V. infusion.
• To prepare 500-mg dose, constitute vial with 10 ml sterile water for injection or normal saline solution for injection, and shake gently to form suspension; resulting concentration is 50 mg/ml. Withdraw suspension using syringe with 21G needle, and add it to infusion bag containing 100 ml normal saline solution or 5% dextrose; shake gently until clear. Final infusion solution concentration is 4.5 mg/ml.
• To prepare 250-mg dose, constitute vial with 10 ml sterile water for injection or normal saline solution for injection, and shake gently to form suspension. Resulting concentration is 50 mg/ml. Withdraw suspension using syringe with 21G needle, and add it to infusion bag containing 100 ml normal saline solution for injection or 5% dextrose; shake gently until clear. Remove 55 ml of this solution from bag and discard. Infuse remaining solution, which contains 250 mg (4.5 mg/ml).
• To prepare infusions in Baxter Minibag Plus infusion bags, see infusion bag manufacturer's instructions.
• Know that infusion solutions range from clear and colorless to clear and slightly yellow. Color variations within this range don't affect product potency.
• Don't mix with or physically add to solutions containing other drugs.
• Don't administer by inhalation.

Adverse reactions

CNS: headache

CV: phlebitis

GI: nausea, diarrhea, oral candidiasis, Clostridium difficile-associated diarrhea

GU: vulvomycotic infection

Hematologic: anemia

Respiratory: pneumonitis (with inhalation use)

Skin: rash, allergic or bullous dermatitis, erythema, macular and papular eruptions, urticaria, erythema multiforme

Other: hypersensitivity reactions (including anaphylaxis)

Interactions

Drug-drug.Probenecid: reduced doripenem renal clearance

Valproic acid: decreased valproic acid level and loss of seizure control

Drug-diagnostic tests.ALT, AST, liver enzymes, transaminases: increased levels

Patient monitoring

• Closely monitor patient for diarrhea.

If allergic reaction occurs, discontinue drug and intervene for serious anaphylactic reactions by giving epinephrine and taking other emergency measures as ordered and needed, including oxygen, I.V. fluids and antihistamines, corticosteroids, pressor amines, and airway management.
• Monitor renal function in patients with moderate to severe renal impairment.

Patient teaching

Tell patient to immediately report rash, diarrhea, or difficulty breathing.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

doripenem

(do-ri-pen-em) ,

Doribax

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: carbapenems
Pregnancy Category: B

Indications

Infections caused by susceptible organisms including:
  • complicated intra-abdominal infections,
  • complicated urinary tract infections, including pyelonephritis.

Action

Inhibits bacterial cell wall formation.

Therapeutic effects

Bactericidal action against susceptible bacteria.
Active against the following gram-negative organisms: Acinetobacter baumanii, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.Also active against the following gram-positive organisms: Streptococcus constellatus and S. intermedius.Anaerobic spectrum includes Bacteroides caccae, B. fragilis, B. thetaiotaomicron, B.uniformis, B. vulgatus, and Peptostreptococcus micros.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Penetrates renal and peritoneal and retroperitoneal tissues and fluids.
Metabolism and Excretion: 71% excreted unchanged in urine; minimal metabolism.
Half-life: 1 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IVunknownend of infusion8 hr*
*Normal renal function

Contraindications/Precautions

Contraindicated in: Hypersensitivity to doripenem, other carbapenems, or beta-lactams.
Use Cautiously in: Renal impairment (↑ risk of seizures; dose reduction recommended if CCr <50 mL/min); Geriatric: Consider age-related ↓ in renal function when choosing dose; Lactation: Use cautiously during lactation; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • headache (most frequent)

Gastrointestinal

  • pseudomembranous colitis (life-threatening)
  • nausea (most frequent)
  • diarrhea
  • ↑ liver enzymes

Hematologic

  • anemia (most frequent)
  • thrombocytopenia

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • toxic epidermal necrolysis (life-threatening)
  • pruritis
  • rash

Local

  • phlebitis

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • infection with resistant organisms
  • superinfection

Interactions

Drug-Drug interaction

May ↓ serum valproate levels (↑ risk of seizures).May ↓ blood levels of valproic acid ; this may result in loss of seizure control.Probenecid ↓ renal clearance and ↑ blood levels.

Route/Dosage

Intravenous (Adults) 500 mg every 8 hr.

Renal Impairment

Intravenous (Adults) CCr 30–50 mL/min—250 mg every 8 hr; CCr >10–<30 mL/min—250 mg every 12 hr.

Availability

Powder for injection (requires reconstitution): 500 mg/vial

Nursing implications

Nursing assessment

  • Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
  • Obtain a history before initiating therapy to determine previous use of and reactions to penicillins, cephalosporins, or carbapenems. Persons with a negative history of penicillin sensitivity may still have an allergic response.
  • Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
  • Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify the physician immediately if these occur. Have epinephrine, an antihistamine, and resuscitative equipment close by in the event of an anaphylactic reaction.
  • Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy.
  • Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.
  • Lab Test Considerations: May cause ↑ AST, ALT, serum alkaline phosphatase levels.
    • May cause anemia.

Potential Nursing Diagnoses

Risk for infection (Indications,  Side Effects)

Implementation

  • Do not confuse Doribax with Zovirax.
  • May switch to appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.
  • Intravenous Administration
  • Intermittent Infusion: Reconstitute 500-mg vial with 10 mL of sterile injection or 0.9% NaCl and shake gently to form a suspension of 50 mg/mL. Diluent: Withdraw the resulting solution using a 21-gauge needle and add it to 100 mL of 0.9% NaCl or D5W; gently shake until clear. For moderate or severe renal impairment, withdraw 55 mL of this solution from the bag and discard. Solution should be clear and colorless to slightly yellow.Concentration: Final concentration is 4.5 mg/mL. Suspension is stable for 1 hr prior to dilution in infusion bag. Administer within 8 hr of reconstitution with 0.9% NaCl or 4 hr of reconstitution with D5W at room temperature or 24 hr if refrigerated; do not freeze.
  • Rate: Administer over 1 hr. Do not administer direct IV.
  • Y-Site Compatibility: acyclovir, amikacin, aminophylline, amiodarone, anidulafungin, atropine, azithromycin, bumetanide, calcium gluconate, carboplatin, caspofungin, ceftaroline, ciprofloxacin, cisplatin, cyclophosphamide, cyclosporine, daptomycin, dexamethasone, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin, enalaprilat, esmolol, esomeprazole, etoposide phosphate, famotidine, fentanyl, fluconazole, fluorouracil, foscarnet, fucosemide, gemcitabine, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, ifosfamide, insulin, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, mannitol, meperidine, methotrexate, methylprednisolone, metoclopramide, metronidazole, micafungin, midazolam, milrinone, morphine, moxifloxacin, norepinephrine, ondansetron, paclitaxel, pantoprazole, phenobarbital, phenylephrine, potassium chloride, ranitidine, sodium bicarbonate, sodium phosphates, tacrolimus, telavancin, tigecycline, tobramycin, vancomycin, voriconazole, zidovudine
  • Y-Site Incompatibility: Do not mix with or physically add to solutions containing other medications,diazepam, potassium phosphates, propofol

Patient/Family Teaching

  • Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy. Consult health care professional before treating with antidiarrheals.
  • Caution patient to notify health care professional if rash or fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several weeks after discontinuation of medication.

Evaluation/Desired Outcomes

  • Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection. Duration may be extended up to 14 days for patients with concurrent bacteremia.

Doribax

a trademark for doripenem.
References in periodicals archive ?
The visiongain pharmaceutical industry analyst, said: "The market will rely on strong uptake of new drugs, such as Ortho-McNeil/Shionogi's Doribax, to drive growth to 2022.
In other action, the FDA's outside panel of experts voted in favor of the safety and efficacy data for Johnson & Johnson's (New Brunswick NJ) Doribax (doripenem for injection) for the treatment of hospital-acquired pneumonia, or nosocomial pneumonia, and ventilator-associated pneumonia.
Honing the model used with Tarivid and Levaquin, Doribax and Ceftobiprole are anticipated to yield Johnson & Johnson the early advantage of an either/or sales proposition in the gram-negative sector.
Shionogi is also the originator of Doribax (doripenem for injection), a carbapenem anti-bacterial for the treatment of complicated intra-abdominal infections and complicated urinary tract infections (US indications).
Johnson & Johnson (New Brunswick NJ) won approval for its Doribax drug to treat infections of the urinary tract and inner abdomen.
This high growth rate, during the period 2005-2010, was primarily attributed to the increase in uptake of premium priced antibiotics such as Levaquin (levofloxacin) and Doribax (doripenem) for the treatment of UTI and the increase in the prevalence and diagnosis of UTI.
Moreover, the study finds that the lack of effective treatment options for these infections is driving increased prescribing of colistin, Pfizer's Tygacil and carbapenems, namely AstraZeneca's Merrem (meropenem, generics), Merck's Primaxin (imipenem-cilastatin, generics) and Janssen's Doribax (doripenem).
This study includes trending analysis from the 2011 study and ten years of AMR proprietary data on hospital formulary inclusion and restriction status for current therapies such as Cubist's Cubicin, Pfizer's Zyvox and Tygacil, Merck's Invanz, Janssen's Doribax, Theravance's Vibativ, last-resort gram-negative infections drugs and generic competition as well as an analysis of anticipated inclusion of emerging antibiotics, including Cubist's CXA-201 and Forest/AstraZeneca's CAZ-AVI.
According to ID specialists, concerns over drug resistance in Gram-negative pathogens has led to the uptake of last-resort drugs and drugs typically used for later-lines of therapy, including meropenem, Merck's Primaxin and Invanz, Janssen's Doribax, Pfizer's Tygacil and colistin.
Payer and Prescriber Perspectives on Opportunities for Growth and Barriers to Success also finds that, with regard to the formulary status of currently marketed antibiotics, premium-priced branded antibiotics -- such as Merck's Invanz, Janssen's Doribax, Bayer's Avelox, Pfizer's Tygacil and Forest's Teflaro -- continue to be subject to prescribing restrictions, likely in efforts to limit inappropriate use, prevent emergence of drug resistance and reduce treatment costs.
Teflaro, Dificid and Doribax Are Cited by the Highest Percentage of Surveyed Hospital Pharmacy Directors as Not Being on Formulary, According to a New Report from Decision Resources
When asked, unaided, of recent changes in prescribing practices and management of Gram-negative infections (GNIs), most physicians noted increased usage of the carbapenems, including meropenem, Merck's Invanz, Janssen's Doribax, and colistin.