Dexrazoxane
**Dexrazoxane** is an intracellular iron chelator and chemoprotectant primarily used in veterinary oncology. * **Cardioprotection**: It is used to attenuate the cumulative, dose-dependent cardiotoxic effects of anthracyclines (such as doxorubicin) in patients showing signs of toxicity, those with pre-existing cardiac disease, or those reaching maximum cumulative dosages. * **Extravasation Management**: It acts as a critical antidote for severe tissue necrosis caused by accidental perivascular administration (extravasation) of doxorubicin. **Clinical Pearls**: * While highly effective for cardioprotection, it is very expensive, which can be cost-prohibitive for many clients. * There is theoretical concern and some human evidence that dexrazoxane may partially protect cancer cells, potentially reducing the antineoplastic efficacy of the chemotherapy protocol.
Mechanism: Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. * Once intracellular, it is **hydrolyzed** into an active ring-opened chelating metabolite. * **Active Metabolite** → **Chelates intracellular iron** → Prevents the formation of the highly reactive **anthracycline-iron complex**. * This prevents the generation of destructive superoxide free radicals → **Protects the myocardium** from oxidative stress and irreversible anthracycline-induced cardiomyopathy. * *Mechanistic Note*: It also acts as a reversible inhibitor of **Topoisomerase II**, which is believed to contribute to its protective effects against severe tissue necrosis during extravasation injuries.
Dosing by species
- Treatment of anthracycline (doxorubicin, epirubicin, etc.) extravasation · 1000 mg/m2 · IV · within 6 hours and again on day 2. Infuse 500 mg/m2 on day 3 · 3 days · Terminate doxorubicin infusion immediately, and infuse intravenously in a separate infusion. Acute surgical evaluation is performed. Dosage recommendations are for human patients, but may apply to veterinary patients.
- Treatment of anthracycline extravasation · 10 times the doxorubicin dose · IV · within 3 hours and again at 24 and 48 hours after extravasation · 48 hours · Anecdotally; significantly reduces local tissue injury.
- Prevention of doxorubicin-induced cardiomyopathy · 10:1 ratio (e.g., 300 mg/m2 of dexrazoxane to 30 mg/m2 doxorubicin) · IV · starting 30 minutes of, and prior to the doxorubicin dose · Given as slow IV bolus (as a short, IV bolus).
- Prevention of doxorubicin-induced cardiomyopathy · 10:1 ratio (e.g., 300 mg/m2 of dexrazoxane to 30 mg/m2 doxorubicin) · IV · starting 30 minutes before doxorubicin is administered · Given as slow IV bolus. Use can be considered in breeds at risk (Shelties, Collies, Australian Shepherds, etc.), dogs exceeding usual cumulative dose cutoff, and cases with preexisting cardiac disease where no effective chemo options exist.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Should not be used unless an anthracycline antineoplastic agent is being used
- Unknown based on monograph, but generally avoid in patients not receiving anthracyclines
Adverse effects
- Additive myelosuppression
- Potential reduction in efficacy of anthracycline antitumor agents
- Testicular atrophy (observed in dogs)
- Myelosuppression (documented in humans)
- Decreased clinical efficacy of anthracycline antineoplastic agents
Drug interactions
- Myelosuppressive agents · Additive myelosuppression may occur when used concurrently.
- Anthracycline antineoplastic agents · May decrease the clinical efficacy of the chemotherapy · moderate
Monitoring
- CBC
- Echocardiogram (if used for cardioprotection)
- ECG (if used for cardioprotection)
- Complete blood count (CBC) for myelosuppression
- Cardiac monitoring (ECG, echocardiogram) if used for cardiotoxicity
- Extravasation site for healing or necrosis
Overdose
Because of the method of administration and drug expense, overdoses are unlikely in veterinary medicine. As there is no known antidote, treatment would be supportive. Potentially, the drug could be removed via hemodialysis.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.