doripenem


doripenem

(do-ri-pen-em) doripenem,

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.