Doxorubicin
**Doxorubicin** is an anthracycline glycoside antibiotic that is one of the most widely used antineoplastic agents in small animal veterinary oncology. Often referred to colloquially as the "Red Devil" due to its bright red color and potent side effect profile, it is utilized either as a single agent or within multi-drug combination protocols. * **Broad-Spectrum Efficacy**: Highly effective against a variety of malignancies including **lymphomas, carcinomas, leukemias, and sarcomas** in both dogs and cats. * **Origin**: Originally isolated from *Streptomyces peucetius*. * **Clinical Pearl**: While it possesses antimicrobial properties, its profound cytotoxicity completely precludes its use as an anti-infective agent. It is a severe **vesicant**; extreme care must be taken to ensure clean intravenous access to prevent devastating extravasation injuries.
Mechanism: Doxorubicin is a cell-cycle non-specific cytotoxic agent with multiple mechanisms of action: * **Topoisomerase II Inhibition**: Intercalates between DNA base pairs and inhibits **topoisomerase II** โ prevents DNA resealing โ causes double-strand DNA breaks โ triggers apoptosis. * **Macromolecular Synthesis Inhibition**: Directly inhibits DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis. * **Free Radical Generation**: Undergoes electron reduction to form anthracycline semiquinone free radicals (often iron-mediated) โ causes severe oxidative stress and lipid peroxidation. * **Clinical Pearl**: The heart is particularly susceptible to doxorubicin-induced oxidative damage because cardiac tissue has inherently low levels of **catalase**, an enzyme necessary to neutralize hydrogen peroxide. This is the primary mechanism behind its cumulative cardiotoxicity.
Dosing by species
- Antineoplastic ยท 30 mg/m2 IV every 2-3 weeks ยท IV ยท every 2-3 weeks ยท Depending on the protocol used. Maximum cumulative dose = 240 mg/m2.
- Lymphoma, sarcomas, carcinomas ยท 30 mg/m2 (Use 1 mg/kg in dogs weighing <10 kg) ยท IV ยท q3wk ยท Maximum total cumulative dose not to exceed 240 mg/m2 ยท Administer over a minimum of 10 minutes into side port of freely running 0.9% NaCl.
- Antineoplastic ยท 20-30 mg/m2 IV every 2-4 weeks ยท IV ยท every 2-4 weeks ยท Depending on the protocol used. Maximum cumulative dose is usually 240 mg/m2.
- Lymphoma, soft tissue sarcomas ยท 1 mg/kg or 20-25 mg/m2 ยท IV ยท q3-5wk ยท Maximum total cumulative dose not to exceed 240 mg/m2 ยท Nephrotoxicity is a major risk in cats, especially at cumulative dosages >100 mg/m2.
- Antineoplastic ยท 30 mg/m2 IV every 3 weeks ยท IV ยท every 3 weeks ยท Depending on the protocol used.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Pre-existing severe myelosuppression
- Impaired cardiac function
- Patients who have reached the total cumulative dose limit of doxorubicin and/or daunorubicin
- Cats with pre-existing renal insufficiency
Adverse effects
- Bone marrow suppression (nadir 5-10 days)
- Cardiac toxicity (acute arrhythmias and cumulative cardiomyopathy)
- Nephrotoxicity (particularly in cats)
- Gastroenteritis (anorexia, vomiting, diarrhea)
- Alopecia
- Stomatitis
- Immediate hypersensitivity/anaphylaxis (primarily in dogs)
- Severe tissue ulceration and necrosis (if extravasated)
Drug interactions
- Antineoplastic agents, other ยท May potentiate the toxic effects of doxorubicin
- Calcium-channel blockers ยท Potentially could increase risk for cardiotoxicity associated with doxorubicin
- Carbamazepine ยท Decreased carbamazepine levels
- Cisplatin ยท Increased risk of toxicity for both agents; carefully weigh risks versus benefits
- Cyclophosphamide ยท May increase doxorubicin blood levels (AUC); doxorubicin may potentiate and prolong hematologic toxicity; coma and seizures have been reported in human patients ยท major
- Cyclosporine ยท Can increase doxorubicin and doxorubicinol (active metabolite) levels
- Glucosamine ยท May reduce doxorubicin effectiveness; use together not recommended in humans
- Phenytoin ยท Doxorubicin may decrease phenytoin levels
- Phenobarbital ยท May increase elimination and reduce blood levels of doxorubicin
- Streptozocin ยท May inhibit doxorubicin metabolism
- Verapamil ยท May increase doxorubicin levels
- Warfarin ยท Increased risk for bleeding
- Zidovudine ยท Increased risk for neutropenia
Monitoring
- Efficacy of tumor response
- CBC with platelets (monitor for myelosuppression, nadir at 5-10 days)
- ECG and/or echocardiogram (especially in dogs with pre-existing heart disease or predisposed breeds)
- Hepatic function prior to and during therapy
- Urinalysis, serum creatinine, and BUN (especially in cats due to nephrotoxicity risk)
Overdose
Inadvertent acute overdosage may be manifested by severe exacerbations of adverse effects (profound myelosuppression, severe GI toxicity, acute cardiotoxicity). A lethal dose for dogs has been reported as 72 mg/m2. **Treatment**: Supportive and symptomatic therapy is required. **Dexrazoxane** may be useful to help prevent cardiac toxicity and should be considered in cases of massive overdose.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.