Class: Protective Agents
ATC Class: V03AF02
VA Class: AN700
Chemical Name: (S)-4,4′-(1-Methyl-1,2-ethanediyl)bis-2,6-piperazinedione
Molecular Formula: C11H16N4O4
CAS Number: 24584-09-6
Uses for Dexrazoxane Hydrochloride
Anthracycline-induced Cardiomyopathy Prophylaxis
Reduction of the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of ≥300 mg/m2 and would benefit from continued doxorubicin therapy (designated an orphan drug by FDA for this use).1 2 3 4 5 6 7 8 9 10 11 16 44 45 47
Dexrazoxane Hydrochloride Dosage and Administration
Consult specialized references for procedures for proper handling and disposal of antineoplastics.1
Handle cautiously; use protective equipment (e.g., latex gloves).1
Administer dexrazoxane ≤30 minutes prior to initiating doxorubicin therapy; administer doxorubicin no later than 30 minutes after the start of dexrazoxane administration.1 2 3 4 5 6 7 8 9 10 11 46 Do not administer doxorubicin prior to dexrazoxane.a
Reconstitute vial containing 250 or 500 mg of dexrazoxane powder with 25 or 50 mL of (1/6) M sodium lactate injection (provided by manufacturer), respectively, to provide a solution containing 10 mg/mL.1
Rate of Administration
Administer in a dosage ratio relative to the IV dose of doxorubicin hydrochloride.1
Prophylaxis of Anthracycline-induced Cardiomyopathy
Prophylaxis of Anthracycline-induced Cardiomyopathy
Maximum 1000 mg/m2 every 3 weeks was administered during clinical trials.a
Reduced doxorubicin dose recommended in patients with hyperbilirubinemia; proportionally reduce dexrazoxane dosage maintaining 10:1 dexrazoxane to doxorubicin ratio.a
Moderate to severe renal impairment (Clcr <40 mL/min): Reduce dosage ratio to 5:1 dexrazoxane to doxorubicin (e.g., 250 mg/m2 dexrazoxane if 50 mg/m2 doxorubicin is administered).a
Not studied in those undergoing dialysis.a
No dosage adjustments except those related to renal impairment.a (See Renal Impairment under Dosage and Administration.)
Cautions for Dexrazoxane Hydrochloride
Use with chemotherapy regimens that do not contain an anthracycline.a
May add to myelosuppression caused by chemotherapeutic agents; perform CBCs frequently.a
Effectiveness of Cytotoxic Regimens
Concurrent use of dexrazoxane with the initiation of fluorouracil, doxorubicin, and cyclophosphamide (FAC) therapy may interfere with the antitumor efficacy of the regimen; such use is not recommended.a (See Prophylaxis of Anthracycline-induced Cardiotoxicity under Uses.)
Use of dexrazoxane does not eliminate potential for anthracycline induced cardiac toxicity; monitor cardiac function carefully.a
Possible increased risk of secondary malignancies; acute myeloid leukemias, lymphomas, and cutaneous carcinomas reported in patients treated chronically with oral razoxane, a racemic mixture of which dexrazoxane is the S(+)-enantiomer.a
Safety and efficacy not established.a
Response in patients >65 years of age does not appear to differ from that in younger adults; however, use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.a
Pharmacokinetics not evaluated; dosage adjustments may be required in patients with hyperbilirubinemia.a (See Hepatic Impairment under Dosage and Administration.)
Decreased clearance; dosage adjustments necessary in patients with moderate to severe renal impairment (Clcr <40 mL/min).a (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Alopecia, nausea, vomiting, fatigue/malaise, anorexia, stomatitis, fever, infection, diarrhea, pain on injection, sepsis, neurotoxicity.a
Interactions for Dexrazoxane Hydrochloride
No significant change in pharmacokinetics of doxorubicin and its predominant metabolite reported with concurrent use of dexrazoxane.a
Dexrazoxane Hydrochloride Pharmacokinetics
Distributed primarily in total body water.a
Plasma Protein Binding
Not bound to plasma proteins.a
Metabolized to a diacid-diamide cleavage product and two monoacid-monoamide ring products.a
Excreted principally in urine as unchanged drug (42%), a diacid-diamide cleavage product, and two monoacid-monoamide ring products.a
Reconstituted or diluted solutions are stable for 6 hours at 15–30°C or under refrigeration (2–8°C).1
Discard unused solutions.1
For information on systemic interactions resulting from concomitant use, see Interactions.
Dextrose 5% in water
Sodium chloride 0.9%
Cardioprotective agent that readily penetrates cell membranes; however, exact mechanism of cardioprotective effect not clearly established.a
Converts intracellularly to a ring-opened bidentate chelating agent that may prevent anthracycline-induced cardiotoxicity, at least in part, by chelating free iron and thus preventing the formation of the anthracycline-iron complex and resultant free radical generation.a 1 2 3 4 5 7 11 13 16 38 40 42
Advice to Patients
Importance of recognizing and reporting signs and symptoms of CHF.a
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.a
Importance of informing patients of other important precautionary information. (See Cautions)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
For injection, for IV use
250 mg (of dexrazoxane)
Zinecard (with 25 mL sodium lactate injection 0.167 Molar [M/6] diluent)
500 mg (of dexrazoxane)
Zinecard (with 50 mL sodium lactate injection 0.167 Molar [M/6] diluent)
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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