ZINECARD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZINECARD (ZINECARD).
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.
| 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. |
| Molecular Weight | 268.3 |
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. |
| 1st trimester | ZINECARD (dexrazoxane) is generally avoided during the first trimester due to teratogenic potential based on animal studies. Use only if clearly needed and no alternative exists. |
| 2nd trimester | Limited human data; animal studies show fetal harm. Risk-benefit assessment required. May be used in life-threatening situations where benefit outweighs risk. |
| 3rd trimester | Similar to second trimester; avoid unless necessary. Potential for fetal toxicity. Consider maternal benefit. |
Clinical note
Comprehensive clinical and safety monograph for ZINECARD (ZINECARD).
| Placental transfer | Crosses placenta in animals; human data limited. Likely transferred due to low molecular weight. |
| Breastfeeding | Not recommended during breastfeeding due to unknown excretion in human milk and potential for serious adverse reactions in nursing infants. Discontinue drug or discontinue nursing. |
■ 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.
| Serious Effects |
Hypersensitivity to dexrazoxane or any componentConcurrent use with non-anthracycline chemotherapeutic agents (not recommended due to lack of benefit)
| 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. |
| Food/Dietary | No known food interactions. Maintain adequate hydration as directed by your healthcare provider. |
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| Lactation Rating | L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential prior to each cycle due to myelosuppression. Monitor liver function tests (LFTs) and renal function. Assess cardiac function with echocardiogram or MUGA scan at baseline and periodically due to potential cardiotoxicity. For fetal monitoring, ultrasound for growth and amniotic fluid volume if used during pregnancy. |
| Fertility Effects | Dexrazoxane may impair fertility in males and females based on animal studies (testicular atrophy, ovarian toxicity). In humans, amenorrhea and gonadal dysfunction reported. Potential for reduced spermatogenesis and ovarian failure. |
| Clinical Pearls | Administer as a slow IV push (over at least 5 minutes) to minimize hypotensive effects. Use only in patients receiving doxorubicin with a cumulative dose ≥300 mg/m². Monitor left ventricular ejection fraction (LVEF) at baseline and periodically. Do not substitute for doxorubicin dose reduction. |
| Patient Advice | This medication is used to reduce the risk of heart damage from doxorubicin chemotherapy. · You will receive this drug as an intravenous injection before your doxorubicin infusion. · Possible side effects include temporary injection site pain, nausea, and flushing. · Report any symptoms of heart failure such as shortness of breath, swelling in ankles or legs, or rapid weight gain. · This drug does not reduce other side effects of chemotherapy such as low blood counts or hair loss. |