dexrazoxane


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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.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.

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)

ROUTEONSETPEAKDURATION
IVrapid unknownunknown

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.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
- Nashville, Tennessee-based specialty pharmaceutical company Cumberland Pharmaceuticals has expanded its medical specialties to include oncology-related medications with two initial supportive care medications: Ethyol (amifostine) injection and Totect (dexrazoxane hydrochloride) injection, the company said.
He received dexrazoxane for cardioprotection prior to each doxorubicin infusion for a total cumulative dose of 6 g/[m.sup.2].
have obtained FDA approval for Totect (dexrazoxane hydrochloride) in the U.S.
Indeed, in hypertensive rats, DOX treatment induces an increase of dendritic cells, suggesting that DOX-induced damage in cellular membranes could stimulate the immune response, which is prevented by the pretreatment with an antioxidant, dexrazoxane [74].
Currently, the iron chelator dexrazoxane (DZR) is the only known drug that alleviates anthracycline-induced myocardial injury, without compromising the antineoplastic efficacy of anthracyclines [3].
The team also found that dexrazoxane has proven helpful in preventing many of the cardiotoxic effects of anthracycline treatment, without reducing its anticancer effects.
7 March 2016 - UK-based pharmaceutical and services company Clinigen Group plc (AIM: CLIN) has acquired Totect (dexrazoxane) from drugmaker Biocodex USA, the company said.
The most promising solution for preventing cardiotoxicity is the coadministration of dexrazoxane, an iron chelating agent that reduces the formation of anthracycline-iron complexes [20, 21].
Uma possibilidade promissora e o tratamento com dexrazoxane, um quelante de radicais livres cardioprotetor em adultos que recebem terapia com antraciclicos.
She was then switched to dexrazoxane, doxorubicin, and ifosfamide, which resulted in a dramatic resolution of the neoplastic lesion.
The drug dexrazoxane can reduce the occurrence of long-term heart damage in girls undergoing treatment for high-risk acute lymphoblastic leukemia (ALL).
Dexrazoxane reduces the formation of free oxygen radicals induced by the doxorubicin-iron complex and the chronic cardiotoxic effects of doxorubicin in experimental and clinical studies (11), (45).