ZINECARD

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZINECARD (ZINECARD).

How it works

Dextrazoxane is a cardioprotective agent. It is a derivative of EDTA that chelates iron, reducing iron-dependent free radical formation that causes anthracycline-induced cardiotoxicity. It also inhibits topoisomerase II beta, which may contribute to its cardioprotective effects.

What the body does with it

Metabolism	Hepatic metabolism via the aldehyde oxidase and xanthine oxidase pathways. Not significantly metabolized by CYP450 enzymes.
Excretion	Renal: approximately 50-60% as unchanged drug; fecal: negligible; biliary: minimal.
Half-life	Terminal elimination half-life: 2.5 to 3.0 hours in patients with normal renal function; clinically, elimination may be prolonged in renal impairment.
Protein binding	Less than 10% bound to plasma proteins.
Volume of Distribution	Volume of distribution: 0.6 to 0.8 L/kg, indicating distribution into total body water.
Bioavailability	Not applicable; administered intravenously; oral bioavailability is negligible due to extensive first-pass metabolism.
Onset of Action	Intravenous: within 30 minutes of administration.
Duration of Action	Duration of cardioprotective effect: up to 24 hours following a single dose; clinical protection is observed during and after doxorubicin administration.

Classification & Brands

Dosing & administration

500-1000 mg/m² intravenously once daily for 3 consecutive days, beginning prior to doxorubicin administration.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥10 mL/min); safety not established in severe (CrCl <10 mL/min) or dialysis-dependent patients.
Liver impairment	No specific guideline; use caution with severe impairment (Child-Pugh C) due to limited data.
Pediatric use	Same as adult dosing based on body surface area; dose is 500-1000 mg/m² IV once daily for 3 days.
Geriatric use	No specific dose adjustment; monitor renal function and volume status closely due to potential age-related renal decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZINECARD (ZINECARD).

Breastfeeding	Not known whether dexrazoxane is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio not available.
Teratogenic Risk	No adequate and well-controlled studies in pregnant women. Animal studies have not been reported. ZINECARD (dexrazoxane) is classified as FDA Pregnancy Category C. Risk cannot be ruled out. Potential fetal harm based on mechanism of action (topoisomerase II inhibition) suggests avoiding use in first trimester. Second and third trimester risks are unknown; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

Risk of secondary malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Do not use with chemotherapy regimens that do not contain an anthracycline. Use only in patients receiving cumulative doxorubicin doses >300 mg/m² for metastatic breast cancer.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to dexrazoxane or any component; use with chemotherapy regimens not containing an anthracycline (due to risk of secondary malignancies).

Clinical Precautions

Precautions

Can cause severe myelosuppression (neutropenia, thrombocytopenia). May enhance the toxicity of other chemotherapeutic agents. Contraceptive use recommended due to potential fetal harm. Monitor cardiac function and complete blood counts regularly.

Clinical Tips & Counseling

Drug interactions

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ZINECARD

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZINECARD (ZINECARD).

How it works

What the body does with it

Metabolism	Hepatic metabolism via the aldehyde oxidase and xanthine oxidase pathways. Not significantly metabolized by CYP450 enzymes.
Excretion	Renal: approximately 50-60% as unchanged drug; fecal: negligible; biliary: minimal.
Half-life	Terminal elimination half-life: 2.5 to 3.0 hours in patients with normal renal function; clinically, elimination may be prolonged in renal impairment.
Protein binding	Less than 10% bound to plasma proteins.
Volume of Distribution	Volume of distribution: 0.6 to 0.8 L/kg, indicating distribution into total body water.
Bioavailability	Not applicable; administered intravenously; oral bioavailability is negligible due to extensive first-pass metabolism.
Onset of Action	Intravenous: within 30 minutes of administration.
Duration of Action	Duration of cardioprotective effect: up to 24 hours following a single dose; clinical protection is observed during and after doxorubicin administration.

Classification & Brands

Dosing & administration

500-1000 mg/m² intravenously once daily for 3 consecutive days, beginning prior to doxorubicin administration.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥10 mL/min); safety not established in severe (CrCl <10 mL/min) or dialysis-dependent patients.
Liver impairment	No specific guideline; use caution with severe impairment (Child-Pugh C) due to limited data.
Pediatric use	Same as adult dosing based on body surface area; dose is 500-1000 mg/m² IV once daily for 3 days.
Geriatric use	No specific dose adjustment; monitor renal function and volume status closely due to potential age-related renal decline.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZINECARD (ZINECARD).

Breastfeeding	Not known whether dexrazoxane is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio not available.
Teratogenic Risk	No adequate and well-controlled studies in pregnant women. Animal studies have not been reported. ZINECARD (dexrazoxane) is classified as FDA Pregnancy Category C. Risk cannot be ruled out. Potential fetal harm based on mechanism of action (topoisomerase II inhibition) suggests avoiding use in first trimester. Second and third trimester risks are unknown; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to dexrazoxane or any component; use with chemotherapy regimens not containing an anthracycline (due to risk of secondary malignancies).