Dexrazoxane

ZINECARD

What it isIntracellular iron chelator; prevents anthracycline cardiomyopathy and treats anthracycline extravasation.

Why this oneIt is the only approved drug that directly reduces anthracycline cardiac injury and can also rescue tissue after extravasation.

What limits itMyelosuppression adds to chemotherapy; verify product and protocol because cardioprotection and extravasation regimens differ.

FDA label

FDA dosing	Population	Start	Target	Max
Reduction of doxorubicin cardiomyopathy risk — only in patients who have received cumulative doxorubicin 300 mg/m2 and are continuing doxorubicin	Adults	IV infusion over 15 min at 10:1 ratio to doxorubicin (e.g. 500 mg/m2 dexrazoxane : 50 mg/m2 doxorubicin), before each doxorubicin dose	IV 10:1 ratio to doxorubicin each cycle	IV 10:1 ratio (5:1 if CrCl <40 mL/min)

Renal CrCl <40 mL/min: reduce dose by 50% (ratio to doxorubicin 5:1, e.g. 250 mg/m2 : 50 mg/m2)

Hepatic With hyperbilirubinemia, reduce dexrazoxane proportionately to the doxorubicin dose reduction (maintain 10:1 ratio)

Sequence-locked to doxorubicin: dexrazoxane first, doxorubicin within 30 min of completion

IV infusion over 15 min — DO NOT administer via IV push
Do not give doxorubicin before dexrazoxane; give doxorubicin within 30 min after dexrazoxane infusion ends
Reconstitute with Sterile Water for Injection (500 mg vial + 50 mL = 10 mg/mL); dilute in Lactated Ringer's to 1.3–3.0 mg/mL
Do not mix with other drugs; gloves recommended — wash skin/mucosae immediately on contact
Reconstituted solution stable 30 min RT (3 h refrigerated); diluted solution 1 h RT (4 h refrigerated); discard unused

Myelosuppression: may add to chemotherapy myelosuppression — obtain CBC before/during each course; dose only when hematologic parameters adequate
Do not use at chemotherapy initiation — may interfere with antitumor activity (lower response rate 48% vs 63% when started with first FAC cycle); use only after cumulative doxorubicin 300 mg/m2
Does not eliminate anthracycline cardiotoxicity — monitor LVEF before and during therapy
Secondary malignancies (AML, MDS) reported
Not indicated in pediatric patients
Embryo-fetal toxicity: effective contraception during treatment (females 6 months, males 3 months after last dose); verify pregnancy status before starting

Pain on injection more frequent vs placebo (12% vs 3%)
More severe leukopenia, granulocytopenia, thrombocytopenia when added to FAC chemotherapy
In combination trials: alopecia, nausea, vomiting, fatigue/malaise, anorexia, stomatitis, fever, infection, diarrhea

Pregnancy Can cause fetal harm (animal teratogenicity at sub-clinical doses); advise of fetal risk; verify pregnancy status before treatment

Lactation Do not breastfeed during treatment and for 2 weeks after last dose

NO BOXED WARNINGS

Direct muscarinic antagonism0 / 4