Mitoxantrone
Mitoxantrone hydrochloride
Also known as: Novantrone · L-232315 · DHAD · dihydroxyanthracenedione dihydrochloride · mitoxantroni hydrochloridum · NSC-301739 · Mitoxantrone hydrochloride · Mitozantrone
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
This dose is based on body surface area (mg/m²). Convert body weight to body surface area before dosing.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Transitional cell carcinoma | 5 mg/m2 IV every 21 days with piroxicam (0.3 mg/kg PO once daily) | IV | every 21 days | — | 🌎 NA |
| Lymphoma, squamous cell carcinoma, transitional cell carcinoma, mammary gland tumors, etc. | 6 mg/m2 IV every 2-3 weeks | IV | every 2-3 weeks | — | 🌎 NA |
| Single rescue agent for lymphoma | 5.5-6 mg/m2 IV every 3 weeks | IV | every 3 weeks | — | 🌎 NA |
| Rescue agent for canine lymphoma | 6 mg/m2 IV every 2-3 weeks | IV | every 2-3 weeks | — | 🌎 NA |
| Transitional cell carcinoma after laser ablation of the primary tumor | 5 mg/m2 IV every 3 weeks for 4 treatments | IV | every 3 weeks | 4 treatments | 🌎 NA |
- Rescue agent for canine lymphoma: Check CBC on day 7 after treatment and the protocol can be repeated on day 14 or 21 if the dog attains complete or partial response. Combining with DTIC (dacarbazine) may improve response rate.
- Transitional cell carcinoma after laser ablation of the primary tumor: Piroxicam was given at a dosage of 0.3 mg/kg PO once daily for the remaining life of the dog.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Soft-tissue sarcomas | 6-6.5 mg/m2 IV given every 3-4 weeks for 4-6 treatments | IV | every 3-4 weeks | 4-6 treatments | 🌎 NA |
| Effective dose (general) | 6.5 mg/m2 IV every 2-3 weeks | IV | every 2-3 weeks | — | 🌎 NA |
| Single rescue agent for lymphoma | 6-6.5 mg/m2 IV every 3 weeks | IV | every 3 weeks | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Mitoxantrone is a synthetic anthracenedione antineoplastic agent used in veterinary oncology for a variety of neoplastic diseases in dogs and cats.
Key Clinical Applications:
- Lymphoma: Often used as a rescue agent when first-line protocols (like CHOP) fail.
- Carcinomas: Efficacious against transitional cell carcinoma (TCC), squamous cell carcinoma, renal adenocarcinoma, and thyroid carcinomas.
- Sarcomas: Used for fibrosarcoma, hemangiopericytoma, and mammary adenocarcinoma.
Clinical Pearls:
- Structurally related to anthracyclines (like doxorubicin) but lacks the amino sugar moiety, which significantly reduces the generation of free radicals. This makes mitoxantrone substantially less cardiotoxic than doxorubicin.
- Because its renal clearance is minimal (~10%), it is a much safer alternative to doxorubicin for cats with pre-existing renal insufficiency.
- Often colloquially referred to as "blue thunder" in veterinary oncology due to its dark blue color and potent efficacy.
Mechanism of action
Mitoxantrone exerts its cytotoxic effects through multiple mechanisms:
- DNA Intercalation: It inserts itself between DNA base pairs, causing structural distortion.
- Electrostatic Interaction: Nonintercalative binding to DNA further stabilizes the drug-DNA complex.
- Topoisomerase II Inhibition: (Pharmacological addition) It inhibits the enzyme Topoisomerase II, preventing the religation of DNA strands and leading to double-strand DNA breaks.
- Synthesis Inhibition: Ultimately inhibits both DNA and RNA synthesis.
While it is not strictly cell-cycle phase specific, it demonstrates the highest activity during the S phase (DNA synthesis phase) of the cell cycle.
Safety & warnings
Contraindications
- Severe pre-existing myelosuppression
- Concurrent active infection
- Significantly impaired cardiac function
- Patients with prior extensive cytotoxic drug or radiation exposure (relative)
- Pregnancy (FDA Category D) and nursing mothers
- Concurrent infection
- Hepatic disease
Adverse effects
- Dose-dependent GI distress (vomiting, anorexia, diarrhea)
- Bone marrow depression (neutropenia, sepsis; nadir typically around day 10)
- Non-regenerative anemia
- Lethargy
- Seizures (specifically noted in cats)
- Blue-green discoloration of urine and sclera (benign)
- Tissue necrosis or phlebitis (if extravasated, though less severe than doxorubicin)
- Rarely: conjunctivitis, jaundice, renal failure, allergic reactions, thrombocytopenia
- Gastrointestinal signs (vomiting, anorexia, diarrhoea)
- Bone marrow depression (WBC nadir generally at 10 days)
- Seizure activity (reported in cats)
- Blue discoloration of urine and sclera (very rare)
- Acute renal failure (anecdotal in cats)
Precautions
Handling Precautions: Mitoxantrone is a cytotoxic agent. Strict adherence to safe handling, administration, and disposal protocols for chemotherapeutic agents is mandatory to protect veterinary personnel.
Extravasation Risk: While generally considered an irritant rather than a severe vesicant like doxorubicin, extravasation can still cause tissue necrosis. Ensure a perfectly placed, clean IV catheter before administration.
Organ Function: Use with caution in patients with impaired hepatic function or hyperuricemia/hyperuricuria.
Drug interactions
Cardiotoxicity risks may be enhanced in patients that have previously received these therapies to the mediastinum.
Concurrent use may significantly increase the risk of severe infection.
Additive bone marrow depression; use with extreme caution.
Increased risk of vaccine-induced infection; should be used with extreme caution or avoided during therapy.
Increased risk of severe bone marrow depression
Increased risk of severe immunosuppression and infection
Chemically incompatible
Monitoring
- CBC with differential and platelets (especially around day 7-10 to check for nadir)
- Tumor measurements/efficacy
- Chest radiographs, ECG, or other cardiac function tests (if cardiac symptomatology is present)
- Liver function tests (if jaundice or clinical signs of hepatotoxicity occur)
- Serum uric acid levels (for susceptible patients)
- Complete Blood Count (CBC), especially WBC count around day 10 post-administration
- Gastrointestinal signs (vomiting, diarrhoea, appetite)
- Renal parameters (especially in cats)
- Hepatic function
- Cardiac function (echocardiogram) if pre-existing disease exists
Pharmacokinetics
Absorption
Administered IV; rapidly and extensively distributed.
Distribution
Highest concentrations found in the liver, heart, thyroid, and red blood cells. Approximately 78% bound to plasma proteins in humans.
Metabolism
Metabolized in the liver.
Elimination
The majority of the drug is excreted unchanged in the urine. Renal clearance is minimal (~10%).
Overdose
Due to the narrow therapeutic index and potential for serious toxicity (profound myelosuppression, severe GI mucosal damage, sepsis), dosage determinations must be made with extreme care. Overdose management is primarily supportive, focusing on aggressive fluid therapy, broad-spectrum antibiotics to manage sepsis secondary to neutropenia, and potentially the use of recombinant granulocyte-colony stimulating factors (G-CSF) to accelerate bone marrow recovery.
Available products
Formulations
- Injection solution concentrate: 2 mg/mL
- Injectable: 2 mg/ml
Human-labeled
- Mitoxantrone HCl for Injection Solution Concentrate: 2 mg/mL, preservative free in 10 mL, 12.5 mL, & 15 mL multi-dose vials (Novantrone®)
- Novantrone 2 mg/ml injection
Regulatory status
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature. Do not mix or use the same IV line with heparin infusions as a precipitate may form. It is not recommended to mix with other IV drugs. While the manufacturer recommends not freezing, one study showed it maintained cytotoxic effects when frozen and thawed over a 12-month period.
Client information
Important Chemotherapy Safety Your pet is receiving a potent chemotherapy drug. The drug and its breakdown products can be found in your pet's urine for up to 6 days and in their feces for up to 7 days after treatment.
- Waste Management: Wear disposable gloves when cleaning up urine, feces, or vomit. Double-bag the waste before placing it in the regular trash. Wash your hands thoroughly afterward.
- Color Changes: You may notice your pet's urine turning a blue-green color, or a slight bluish tint to the whites of their eyes (sclera). Do not panic—this is a normal, harmless effect of the drug's dark blue dye.
- Side Effects to Watch For: Monitor your pet closely for loss of appetite, vomiting, diarrhea, or extreme lethargy. Because this drug lowers white blood cell counts, your pet is at a higher risk for infection.
- When to Call the Vet: Contact your veterinarian immediately if your pet develops a fever, severe vomiting/diarrhea, or if a cat experiences any seizure activity.
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.