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) ,

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)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	unknown	unknown

Contraindications/Precautions

Contraindicated in: Any other type of chemotherapy except other anthracyclines (doxorubicin-like agents);May cause fetal harm

Use 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.

dexrazoxane

/dex·ra·zox·ane/ (-ra-zok´sān) a cardioprotectant used in chemotherapy to counteract doxorubicin-induced cardiomyopathy.

dexrazoxane

a cardioprotective agent.

indications It is prescribed in the protection of women from heart problems caused by doxorubicin treatment of breast cancer.

contraindications It should not be given to patients with an allergy to dexrazoxane or any of its components or who are receiving chemotherapy that does not contain an anthracycline drug.

adverse effects The side effects most often reported include pain on or at the injection site, flushing, bruising, rash, numbness, or general body discomfort.