dexrazoxane


dexrazoxane

 [deks″ra-zok´sān] a derivative of ethylenediaminetetraacetic acid (EDTA) used as a cardioprotectant in antineoplastic therapy to counteract cardiomyopathy induced by doxorubicin; administered intravenously.

dexrazoxane

(dex-ra-zox-ane) dexrazoxane,

Totect

(trade name),

Zinecard

(trade name)

Classification

Therapeutic: cardioprotective agents
Pregnancy Category: D

Indications

Reducing incidence and severity of cardiomyopathy from doxorubicin in women with metastatic breast cancer who have already received a cumulative dose of doxorubicin >300 m g/m2.Treatment of extravasation resulting from IV anthracycline chemotherapy.

Action

Acts as an intracellular chelating agent.

Therapeutic effects

Diminishes the cardiotoxic effects of doxorubicin.Decreased damage from extravasation of anthracyclines.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Unknown.Metabolism and Excretion: Some metabolism occurs; 42% eliminated in urine.Half-life: 2.1–2.5 hr.

Time/action profile (cardioprotective effect)

ROUTEONSETPEAKDURATION
IVrapid unknownunknown

Contraindications/Precautions

Contraindicated in: Any other type of chemotherapy except other anthracyclines (doxorubicin-like agents);May cause fetal harmUse Cautiously in: CCr <40 mL/min (dose ↓required); Lactation: Lactation Pediatric: Safety and effectiveness not established

Adverse Reactions/Side Effects

Hematologic

  • myelosuppression

Local

  • pain at injection site

Miscellaneous

  • malignancy (life-threatening)

Interactions

Drug-Drug interaction

Myelosuppression may be ↑ by antineoplastics or radiation therapy.Antitumor effects of concurrent combination chemotherapy with fluorouracil and cyclophosphamide may be ↓ by dexrazoxane.

Route/Dosage

Cardioprotective

Intravenous (Adults) 10 mg of dexrazoxane/1 mg doxorubicin.

Renal Impairment

Intravenous (Adults) ↓ dose by 50%.

Extravasation Protection

Intravenous (Adults) 1000 mg/m2 (maximum 2000 mg) given on days 1 and 2, and followed by a dose of 500 mg/m2 (maximum 1000 mg) on day 3.

Renal Impairment

Intravenous (Adults CCr <40 mL/min) ↓ dose by 50%.

Availability (generic available)

Injection (Zinecard): 250 mg/vial, 500 mg/vial Injection (Totect): 500 mg/vial

Nursing implications

Nursing assessment

  • Cardioprotective: Assess extent of cardiomyopathy (cardiomegaly on x ray, basilar rales, S gallop, dyspnea, decline in left ventricular ejection fraction) prior to and periodically during therapy.
  • Extravasation protection: Assess site of extravasation for pain, burning, swelling, and redness.
  • Lab Test Considerations: Monitor CBC and platelet count frequently during therapy. Thrombocytopenia, leukopenia, neutropenia, and granulocytopenia from chemotherapy may be more severe at nadir with dexrazoxane therapy.
    • Monitor liver function tests periodically during therapy. May cause reversible ↑ of liver enzymes.

Potential Nursing Diagnoses

Decreased cardiac output (Indications)
Risk for impaired skin integrity (Indications)

Implementation

  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers (see ).
    • Do not administer solutions that are discolored or contain particulate matter. Reconstituted solution and diluted solution are stable in an IV bag for 6 hr at room temperature or if refrigerated. Discard unused solutions.
  • Intravenous Administration
  • pH: 3.5–5.5.
  • Cardioprotective: Doxorubicin should be administered within 30 min following dexrazoxane administration.
  • Diluent: Reconstitute dexrazoxane with 0.167 molar (M/6) sodium lactate injection.Concentration: 10 mg/mL.
  • Rate: Administer via slow IV push.
  • Intermittent Infusion: Diluent: Reconstituted solution may also be diluted with 0.9% NaCl or D5W. Solution is stable for 6 hr at room temperature or refrigeratedConcentration: 1.3–5 mg/mL.
  • Rate: May also be administered via rapid IV infusion over 15–30 min.
  • Additive Incompatibility: Do not mix with other medications.
  • Extravasation Protection: Administer as soon as possible within 6 hr of extravasation. Remove cooling procedures, such as ice packs, at least 15 min before administration to allow sufficient blood flow to area of extravasation.
  • Intermittent Infusion: Diluent: Dilute each vial in 50 mL of diluent provided by manufacturer. Add contents of all vials into 1000 mL of 0.9% NaCl for further dilution. Solution is slightly yellow. Use diluted solutions within 2 hr of dilution. Store at room temperature.
  • Rate: Administer over 1–2 hr.
  • Y-Site Compatibility:
    • alemtuzumab
    • alfentanil
    • amifostine
    • amikacin
    • amiodarone
    • ampicillin
    • ampicillin/sulbactam
    • anidulafungin
    • argatroban
    • arsenic trioxide
    • atracurium
    • azithromycin
    • aztreonam
    • bivalirudin
    • bleomycin
    • bumetanide
    • buprenorphine
    • busulfan
    • buprenorphine
    • calcium chloride
    • calcium gluconate
    • carboplatin
    • carmustine
    • caspofungin
    • cefazolin
    • cefotaxime
    • cefotetan
    • cefoxitin
    • ceftazidime
    • ceftriaxone
    • cefuroxime
    • chloramphenicol
    • chlorpromazine
    • ciprofloxacin
    • cisatracurium
    • cisplatin
    • clindamycin
    • cyclophosphamide
    • cyclosporine
    • cytarabine
    • dactinomycin
    • daptomycin
    • dexmedetomidine
    • digoxin
    • diltiazem
    • diphenhydramine
    • docetaxel
    • dolasetron
    • dopamine
    • doxacurium
    • doxorubicin
    • doxorubicin liposomal
    • doxycycline
    • droperidol
    • enalaprilat
    • ephedrine
    • epinephrine
    • epirubicin
    • eptifibatide
    • srtapenem
    • erythromycin
    • esmolol
    • stoposide
    • famotidine
    • fenoldopam
    • fentanyl
    • fluconazole
    • fludarabine
    • fluorouracil
    • foscarnet
    • fosphenytoin
    • gentamycin
    • glycopyrrolate
    • granisetron
    • haloperidol
    • heparin
    • hetastarch
    • hydralazine
    • hydrocortisone sodium succinate
    • hydromorphone
    • idarubicin
    • ifosfamide
    • imipenem/cilastatin
    • insulin
    • irinotecan
    • isoproterenol
    • ketorolac
    • leucovorin
    • levofloxacin
    • lidocaine
    • linezolid
    • lorazepam
    • magnesium sulfate
    • mannitol
    • mechlorethamine
    • melphalan
    • meperidine
    • meropenem
    • metaraminol
    • methyldopate
    • metoclopramide
    • metoprolol
    • metronidazole
    • midazolam
    • milrinone
    • minocycline
    • mitoxantrone
    • morphine
    • mycophenolate
    • nalbuphine
    • naloxone
    • nesiritide
    • nicardipine
    • nitroglycerin
    • nitroprusside
    • norepinephrine
    • octreotide
    • ondansetron
    • oxaliplatin
    • paclitaxel
    • palonosetron
    • pamidronate
    • pancuronium
    • pemetrexed
    • pentamidine
    • pentazocine
    • phenobarbital
    • phentolamine
    • phenylephrine
    • piperacillin/tazobactam
    • polumyxin B
    • potassium acetate
    • potassium chloride
    • potassium phosphates
    • procainamide
    • prochlorperazine
    • promethazine
    • propranolol
    • quinupristin/dalfopristin
    • ranitidine
    • remifentanil
    • rituximab
    • rocuronium
    • sodium acetate
    • sodium bicarbonate
    • streptozocin
    • succinylcholine
    • sufentanil
    • tacrolimus
    • teniposide
    • theophylline
    • thiotepa
    • ticarcillin/clavulanate
    • tigecycline
    • tirofiban
    • tobramycin
    • vancomycin
    • vasopressin
    • vecuronium
    • verapamil
    • vinblastine
    • vincristine
    • vinorelbine
    • voriconazole
    • zolendronic acid
  • Additive Incompatibility:
    • acyclovir
    • allopurinol
    • aminophylline
    • amphotericin B colloidal
    • amphotericin B lipid complex
    • amphotericin B liposome
    • cefepime
    • dantrolene
    • diazepam
    • dobutamine
    • furosemide
    • ganciclovir
    • methotrexate
    • methylprednisolone
    • nafcillin
    • pantoprazole
    • pentobarbital
    • phenytoin
    • sodium phosphates
    • thiopental
    • trimethoprim/sulfamethoxazole
    • zidovudine

Patient/Family Teaching

  • Explain the purpose of the medication to the patient.
  • Emphasize the need for continued monitoring of cardiac function.
  • Advise patient to notify health care professional if pregnancy is suspected or planned or if breast feeding. Dexrazoxane may be teratogenic. Breast feeding should be avoided during therapy

Evaluation/Desired Outcomes

  • Reduction of incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer.
  • Decrease in late sequalae (site pain, fibrosis, atrophy, and local sensory disturbance) following extravasation of anthracycline chemotherapeutic agents.