dexrazoxane (Rx)

Brand and Other Names:Totect, Zinecard
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

powder for injection

  • 250mg
  • 500mg

Doxorubicin-induced Cardiomyopathy

Zinecard, Totect, and generic

Indicated for reducing 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 who will continue to receive doxorubicin therapy to maintain tumor control

Do not use with initiation of doxorubicin therapy

Infuse IV over 15 minutes before doxorubicin administration

Do not administer via an IV push

Dosage ratio of dexrazoxane to doxorubicin is 10:1 (eg, 500 mg/m2 dexrazoxane to 50 mg/m2 doxorubicin)

Administer doxorubicin within 30 minutes after completion of dexrazoxane infusion

Extravasation

Totect only

Infuse IV over 1-2 hr once daily for 3 consecutive days; begin treatment within 6 hr of extravasation

Initiate first infusion as soon as possible and within 6 hr after extravasation

Day 1: 1000 mg/m2 IV; not to exceed 2000 mg  

Day 2: 1000 mg/m2 IV; not to exceed 2000 mg

Day 3: 500 mg/m2 IV; not to exceed 1000 mg

Dosage Modifications

Renal impairment

  • Mild (CrCl ≥40 mL/min): No dosage adjustment necessary
  • Moderate-to-severe (CrCl <40 mL/min): Reduce dose by 50% (dexrazoxane to doxorubicin ratio reduced to 5:1; such as dexrazoxane 250 mg/m2 to doxorubicin 50 mg/m2)

Hepatic impairment

  • Extravasation (Totect): Not recommended
  • Cardiomyopathy
    • Reduce dosage proportionately (maintaining the 10:1 ratio) in patients with hepatic impairment, since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia

Safety and efficacy not established

Cardiomyopathy Prophylaxis (Orphan)

Orphan designation for prevention of anthracyline-induced cardiomyopathy in children and adolescents

Sponsor

  • Satiscor, LLC; 45 Marine Road; Boston, MA 02127
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Interactions

Interaction Checker

and dexrazoxane

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      Serious - Use Alternative

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            Adverse Effects

            Frequency Not Defined

            Most ADRs due to concurrent antineoplastic treatment

            Injection site pain, phlebitis, and increased myelosuppression are only major specific ADR

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            Warnings

            Contraindications

            Hypersensitivity

            Use (Zinecard) in chemotherapy when an anthracycline is not being administered

            Cautions

            May interfere with activity of antineoplastic drugs; do NOT initiate until cumulative doxorubicin dose reaches 300 mg/m²

            Do NOT give doxorubicin prior to dexrazoxane

            Does not eliminate potential for anthracycline-induced cardiac toxicity; monitor cardiac function carefully

            Secondary malignancies (eg, AML, MDS) reported with combination chemotherapy

            Treatment is associated with leukopenia, neutropenia, and thrombocytopenia; grade 2-4 decreased white blood cells (73%), decreased neutrophils (61%), and decreased platelets (26%) occurred in patients; febrile neutropenia occurred in 2.5% of patients; monitor complete blood counts during treatment; myelosuppression and cytotoxic potential and cytotoxic chemotherapy (with a nadir occurring on days 10-12) may be additive to that of chemotherapy administered alone

            Hypersensitivity reactions including anaphylactic reaction, angioedema, skin reactions, bronchospasm, respiratory distress, hypotension and loss of consciousness have occurred in patients treated with dexrazoxane products and anthracyclines; previous history of allergy to dexrazoxane products should be carefully considered prior to administration; consider permanent discontinuation in patients with severe hypersensitivity reactions

            Therapy has not been studied in patients with hepatic impairment; since liver dysfunction (increases in transaminases and bilirubin) may occur (especially after doses of above 1000 mg/m² dexrazoxane), it is recommended that routine liver function tests be performed before each administration of dexrazoxane in patients with known liver function disorders; use in patients with hepatic impairment not recommended

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            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; limited available data in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes

            In animal reproduction studies, intravenous administration of dexrazoxane to pregnant rats and rabbits during organogenesis resulted in teratogenicity at maternal doses that were approximately 0.1 and 0.2 times, respectively, the human dose of 1000 mg/m²; advise pregnant women of potential risk to fetus

            Pregnancy testing

            • Perform pregnancy testing prior to initiation of chemotherapy; repeat pregnancy testing prior to administration of therapy not recommended, because treatment of extravasation of anthracycline chemotherapy should not be delayed

            Contraception

            • Females: Therapy can cause fetal harm when administered to a pregnant woman; because of potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment and for 6 months following the final dose
            • Males: Because of potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months following the final dose

            Infertility

            • Males: Based on findings in animal studies, therapy may impair fertility in males of reproductive potential; not known whether these effects on fertility are reversible

            Lactation

            There are no data on presence in human milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions, such as myelosuppression, in a breastfed child, advise women not to breastfeed during treatment and for 2 weeks following final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            EDTA derivative; intracellular chelating agent; exact mechanism not understood

            Pharmacokinetics

            Half-Life: 2-2.5 hr

            Peak Plasma: 36.5 mcg/mL

            Protein Bound: No

            Vd: 22.4 L/m²

            Renal Clearance: 3.35 L/hr/sq.meter

            Excretion: Urine (42%)

            Dialyzable: Yes

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            Administration

            IV Incompatibilities

            Do not mix or administer with any other drug during infusion

            IV Preparation

            Visually inspect products for particulate matter and discoloration before administration; discard solutions containing a precipitate

            Use caution when handling and preparing reconstituted solution; use of gloves is recommended

            If powder or solutions contact the skin or mucosae, wash exposed area immediately and thoroughly with soap and water; follow special handling and disposal procedures

            Totect

            • Extravasation
              • Reconstitute each vial with 50 mL of Sterile Water for Injection (SWI) to obtain 10 mg/mL of reconstituted solution
              • Reconstituted solution contains no antibacterial preservatives and should be further diluted within 30 min after initial reconstitution
              • Withdraw calculated volume from reconstituted solution and further dilute into an infusion bag containing 1000 mL of Lactated Ringer injection (LR); do not mix with any other drugs
            • Doxorubicin-induced cardiomyopathy
              • Reconstitute each vial with 50 mL of SWI; reconstituted solution contains 10 mg/mL
              • Reconstituted solution contains no antibacterial preservatives and should be further diluted within 30 min after initial reconstitution
              • Withdraw calculated volume from the reconstituted solution and further dilute to a concentration of 1.3-3 mg/mL in LR
              • Do not mix with any other drugs

            Zinecard, generic

            • Reconstitute with 25 mL of SWI for a 250-mg vial and 50 mL of SWI for a 500-mg vial; reconstituted solution contains 10 mg/mL
            • Reconstituted solution contains no antibacterial preservatives and should be further diluted within 30 min after initial reconstitution
            • Withdraw calculated volume from the reconstituted solution and further dilute to a concentration of 1.3-3 mg/mL in LR
            • Do not mix with any other drugs

            IV Administration

            Do not mix with other drugs

            Doxorubicin-induced cardiomyopathy

            • Totect, Zinecard, generic
            • Do not administer IV push
            • Infuse final diluted solution IV over 15 minutes before administering the doxorubicin
            • Administer doxorubicin within 30 minutes after the completion of dexrazoxane infusion

            Extravasation

            • Totect only
            • Remove cooling procedures (eg, ice packs) if used, from extravasation area at least 15 minutes before administration in order to allow sufficient blood flow to the area of extravasation
            • Infuse final diluted solution IV over 1-2 hr at room temperature and normal light conditions in a large caliber vein in an extremity/area other than the one affected by the extravasation
            • Start Day 2 and Day 3 treatment at the same hour (+/- 3 hr) as on the first day
            • Regularly examine for extravasation after treatment and until resolution
            • If vesicant compounds other than anthracyclines are being used through the same IV access, (eg, vincristine, mitomycin, and vinorelbine), consider treatments for these other vesicant compounds
            • Not effective against the effects of vesicants other than anthracyclines

            Storage

            Zinecard

            • Unused vials
              • Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
              • Protect from light
              • Keep vial in carton until ready for use
            • Reconstituted vials
              • Stable for 30 min at room temperature or up to 3 hr from time of reconstitution when refrigerated at 2-8ºC (36-46ºF)
              • pH of resultant solution is 1 to 3
            • Reconstituted solution
              • Use immediately after further dilution
              • If not used immediately, stable for 4 hr from time of preparation when stored at room temperature or for up to 12 hr when refrigerated at 2-8ºC (36-46ºF)
              • For extravasation use: Infusion solutions have a pH of 3.5 to 5.5

            Totect

            • Unused vials

              • Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
              • Protect from light
              • Keep vial in carton until ready for use
            • Reconstituted vials

              • Stable for 30 min at room temperature
            • Reconstituted solution

              • Use immediately after further dilution
              • If not used immediately, stable for 4 hr from time of preparation when stored at room temperature or for up to 12 hr when refrigerated between 2-8ºC (36-46ºF)
              • For extravasation use: Infusion solutions have a pH of 3.5 to 5.5
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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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