DEXRAZOXANE

DEXRAZOXANE
(dex-ra-zox'ane)
Zinecard
Classifications: chelating agent; chemoprotective agent; cardioprotective for doxorubicin;
Therapeutic: cardioprotective for doxorubicin

Pregnancy Category: C

Availability

250 mg, 500 mg vials for injection

Action

A derivative of EDTA that readily penetrates cell membranes. Dexrazoxane is converted intracellularly to a chelating agent that interferes with iron-mediated free radical generation thought to be partially responsible for one form of cardiomyopathy.

Therapeutic Effect

Cardioprotective effect is related to its chelating activity.

Uses

Reduction of cardiomyopathy associated with a cumulative doxorubicin dose of 300 mg/m2.

Contraindications

Chemotherapy regimens that do not contain anthracycline, pregnancy (category C), lactation.

Cautious Use

Myelosuppression, elderly; prior radiation or chemotherapy; renal failure or impairment. Safety and efficacy in children have not been established.

Route & Dosage

Cardiomyopathy
Adult: IV 10 parts dexrazoxane to 1 part doxorubicin or 500 mg/m2 for every 50 mg/m2 of doxorubicin

Renal Impairment
Clcr <40 mL/min: use a 5:1 ratio of dexrazoxane to doxorubicin

Administration

Intravenous
  • Wear gloves when handling dexrazoxane. Immediately wash with soap and water if drug contacts skin or mucosa.
  • Doxorubicin dose MUST be started within 30 min of beginning dexrazoxane.

PREPARE: Direct: Reconstitute by adding 25 or 50 mL of 0.167 M sodium lactate injection (provided by manufacturer) to the 250- or 500-mg vial, respectively, to produce a 10-mg/mL solution.  IV Infusion: Further dilute with NS or D5W in an IV bag to a concentration of 1.3–5.0 mg/mL for infusion.  

ADMINISTER: Direct: Give slow IV push.  IV Infusion: Give over 10 min.  

  • Store reconstituted solutions for 6 h at 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

All: Adverse effects of dexrazoxane are difficult to distinguish from those of the chemotherapeutic agents. Pain at injection site, leukopenia, granulocytopenia, and thrombocytopenia appear to occur more frequently with the addition of dexrazoxane than with placebo.

Pharmacokinetics

Distribution: Not protein bound. Metabolism: In liver. Elimination: 42% in urine. Half-Life: 2–2.5 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor cardiac function. Drug does not eliminate risk of doxorubicin cardiotoxicity.
  • Lab tests: Monitor hepatic, renal, and hematopoietic status throughout course of therapy.
  • Note: Adverse effects are likely due to concurrent cytotoxic drugs rather than dexrazoxane.

Patient & Family Education

  • Report any of the following to physician: Worsening shortness of breath, swelling extremities, or chest pains.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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