Doxorubicin Hydrochloride — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	IV	30 mg/m²	Every 3 weeks	Duration: As per protocol (e.g., up to 5 cycles) Notes: Administer as a slow IV infusion over 20-30 minutes. Monitor for extravasation. Dose may be reduced in patients with hepatic impairment or prior cardiotoxicity.
Cat	IV	20-25 mg/m²	Every 3 weeks	Duration: As per protocol Notes: Cats are more sensitive to doxorubicin; lower doses are recommended. Administer as a slow IV infusion. Monitor renal function.
Horse	IV	30-60 mg/m²	Every 3 weeks	Duration: As per protocol Notes: Use with caution; limited data. Administer as a slow IV infusion. Monitor for cardiotoxicity.
Cattle	IV	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires careful consideration and monitoring.
Small Ruminants	IV	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires careful consideration and monitoring.
Rabbit	IV	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires careful consideration and monitoring.
Bird/Poultry	IV	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires careful consideration and monitoring.
Exotic/Other	IV	Not established	Not established	Duration: Not established Notes: Not commonly used; extra-label use requires careful consideration and monitoring.

Clinical Indications & Species Uses

General Indications

Treatment of various neoplasms in companion animals, particularly lymphomas and sarcomas

Dog (Canine)

Lymphoma
Sarcoma (e.g., hemangiosarcoma, osteosarcoma)
Mammary carcinoma
Transitional cell carcinoma
Multiple myeloma
Leukemia

Cat (Feline)

Lymphoma
Mammary carcinoma
Sarcoma (e.g., fibrosarcoma)
Leukemia

Horse (Equine)

Squamous cell carcinoma
Lymphoma
Sarcoma (limited use)

Pharmacology & Mechanism of Action

Drug Class: Anthracycline antibiotic | Pharmacological Group: Antineoplastic agent

Mechanism of Action: Doxorubicin intercalates between DNA base pairs, inhibiting DNA and RNA synthesis by blocking topoisomerase II activity. It also generates free radicals (reactive oxygen species) that cause DNA damage and lipid peroxidation, leading to cell death. Additionally, it binds to cell membranes and alters their fluidity, contributing to its cytotoxic effects.

Pharmacodynamics: Doxorubicin is a cell cycle non-specific agent, but it is most active during the S phase of the cell cycle. It induces apoptosis in rapidly dividing cells, including cancer cells, but also affects normal tissues with high proliferative rates (e.g., bone marrow, gastrointestinal epithelium, hair follicles). Its cardiotoxic effects are attributed to oxidative stress and mitochondrial dysfunction in cardiac myocytes.

⚡ Pharmacokinetics Summary

Absorption: Doxorubicin is not absorbed orally; it is administered intravenously. After IV administration, it achieves high plasma concentrations rapidly.

Distribution: Doxorubicin is extensively distributed into tissues, with highest concentrations in the liver, spleen, kidney, lung, and heart. It crosses the blood-brain barrier poorly. It binds to DNA and cellular components, leading to a large volume of distribution.

Metabolism: Doxorubicin is extensively metabolized in the liver by aldo-keto reductases to doxorubicinol (an active metabolite) and other inactive metabolites. The metabolism is primarily hepatic, with some extrahepatic metabolism.

Excretion: Doxorubicin and its metabolites are excreted primarily in bile and feces. Approximately 40-50% of the dose is eliminated in bile, and about 5-10% is excreted in urine. In animals with hepatic impairment, clearance is reduced.

Half-Life: The terminal half-life in dogs is approximately 20-30 hours; in cats, it is around 20-30 hours as well. In horses, the half-life is shorter, around 1-2 hours.

Bioavailability: Oral bioavailability is negligible; therefore, it is only administered intravenously.

Protein Binding: Doxorubicin is approximately 70-80% bound to plasma proteins, primarily albumin.

Available Formulations & Strengths

Injectable Solution 2 mg/mL (as hydrochloride) (IV)

Lyophilized Powder for Injection 10 mg, 20 mg, 50 mg vials (IV)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to doxorubicin or other anthracyclines
Severe hepatic impairment
Severe cardiac disease (e.g., cardiomyopathy, congestive heart failure)
Severe myelosuppression (e.g., neutropenia, thrombocytopenia)
Pregnancy and lactation (teratogenic and embryotoxic)
Concurrent use with other cardiotoxic agents (e.g., cyclophosphamide at high doses)

Warnings & Clinical Precautions:

Doxorubicin is a vesicant; extravasation can cause severe tissue necrosis. Administer via a secure IV catheter and monitor closely.
Cardiotoxicity is dose-limiting; cumulative doses should not exceed 180-240 mg/m² in dogs and 150-200 mg/m² in cats.
Myelosuppression is common; monitor complete blood counts regularly.
Hepatic and renal function should be assessed before and during therapy.
Use with caution in animals with pre-existing heart disease, obesity, or advanced age.
Doxorubicin is immunosuppressive; avoid live vaccines during therapy.
Handle and dispose of doxorubicin as hazardous waste; wear protective equipment.
In cats, doxorubicin can cause nephrotoxicity; monitor renal function.
In horses, doxorubicin may cause severe local reactions if extravasation occurs.

Adverse Effects & Reactions

Common:

Myelosuppression (neutropenia, thrombocytopenia, anemia)
Gastrointestinal effects (nausea, vomiting, diarrhea, anorexia)
Alopecia (especially in dogs)
Reddish-orange discoloration of urine (not harmful)
Phlebitis at injection site

Serious / Severe:

Cardiotoxicity (arrhythmias, cardiomyopathy, congestive heart failure)
Extravasation injury (tissue necrosis, sloughing)
Severe myelosuppression leading to sepsis or bleeding
Nephrotoxicity (especially in cats)
Hepatotoxicity
Anaphylactic reactions (rare)

Rare:

Secondary malignancies (e.g., leukemia)
Pulmonary fibrosis
Neurotoxicity
Teratogenic effects

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Cyclophosphamide	Increased risk of cardiotoxicity and myelosuppression; may enhance antitumor effect but requires careful monitoring.	High
Other cardiotoxic drugs (e.g., mitoxantrone, trastuzumab)	Additive cardiotoxicity; avoid concurrent use or reduce dose.	High
Hepatotoxic drugs (e.g., azathioprine, ketoconazole)	Increased risk of hepatotoxicity; monitor liver function.	Moderate
Phenobarbital	May increase metabolism of doxorubicin, reducing efficacy; monitor therapeutic response.	Moderate
Digoxin	Doxorubicin may reduce digoxin absorption and increase its clearance; monitor digoxin levels.	Moderate
NSAIDs (e.g., carprofen)	Increased risk of gastrointestinal ulceration and bleeding due to additive effects on GI mucosa.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Severe myelosuppression (pancytopenia)
Cardiac arrhythmias
Congestive heart failure
Severe gastrointestinal toxicity (vomiting, diarrhea, hemorrhage)
Hepatotoxicity
Renal failure

Emergency Treatment Protocol: There is no specific antidote for doxorubicin overdose. Treatment is supportive and symptomatic. Hospitalize the animal, provide IV fluids, monitor cardiac function (ECG, echocardiography), and manage myelosuppression with colony-stimulating factors (e.g., filgrastim) if available. Administer antiemetics, GI protectants (e.g., sucralfate), and antibiotics if infection develops. For extravasation, apply cold compresses and consider local infiltration of dimethyl sulfoxide (DMSO) or dexrazoxane (if available). In severe cases, consider referral to a veterinary oncologist.

Food Animal Withdrawal Times

Doxorubicin is not approved for use in food animals. Use in food animals is prohibited or requires a very long withdrawal period; however, due to its hazardous nature, it is not recommended. No established withdrawal times are available.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (15-30°C) in a dry place. Protect from light.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Reconstituted solutions should be stored under refrigeration (2-8°C) and used within 24-48 hours. Protect from light. Do not freeze. Discard unused portions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. Used extra-label in veterinary medicine.

Extra-Label (Off-Label) Use: In the US, doxorubicin is not FDA-approved for veterinary use but is used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA). It must be prescribed by a licensed veterinarian within a valid veterinarian-client-patient relationship. For food animals, extra-label use is prohibited if the drug is not approved for that species and if there is no established withdrawal time.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Doxorubicin is a potent chemotherapeutic agent used primarily in dogs and cats for various malignancies. It is administered intravenously with strict precautions to prevent extravasation. Pre-treatment evaluation should include a complete blood count, serum biochemistry, urinalysis, and cardiac assessment (echocardiography) in animals with risk factors. Dose adjustments are necessary for hepatic or renal impairment. The most significant adverse effects are dose-dependent cardiotoxicity and myelosuppression. Cumulative lifetime doses should be tracked to minimize cardiotoxic risk. In cats, lower doses are used due to increased sensitivity. Supportive care, including antiemetics and appetite stimulants, may be needed. Due to its hazardous nature, handling and disposal must follow safety guidelines. Prognosis depends on tumor type and stage; doxorubicin is often used in combination protocols (e.g., CHOP for lymphoma).

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)