Fluorouracil
5-fluorouracil
Also known as: Adrucil · Efudix · 5-FU · 5-fluorouracil · fluorouracilo · fluorouracilum · NSC-19893 · Ro-2-9757 · WR-69596
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 |
|---|---|---|---|---|---|
| Canine mammary carcinoma (in combination with doxorubicin and cyclophosphamide-FAC protocol), dermal squamous cell carcinoma and GI tract tumors | 150 mg/m2 IV weekly, or 5-10 mg/kg IV weekly | IV | weekly | — | 🌎 NA |
| Systemic carcinomas | 150 mg/m2 | IV | once weekly OR once every 3 weeks when combined with carboplatin | 6 weeks (if used weekly) | 🌍 EU |
| Basal cell and squamous cell carcinoma | Apply to affected area | topical | q24h | As directed by oncologist | 🌍 EU |
- Systemic carcinomas: Reduce dose by half in patients with liver, renal, or bone marrow impairment.
- Basal cell and squamous cell carcinoma: Wear gloves when applying. Prevent the dog from licking the area.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| ALL | CONTRAINDICATED | ALL | — | — | 🌎 NA |
| All indications | DO NOT USE | PO/IM/IV/SC/topical | null | null | 🌍 EU |
- ALL: Do NOT use in any form on cats
- All indications: Strictly contraindicated. Causes potentially fatal neurotoxicity.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Intratumoral injection with epinephrine into certain skin neoplasms (squamous cell carcinoma, melanoma, sarcoid) | 0.3 mL of 1:1000 epinephrine is added to each mL of 5-FU solution up to a maximum of 3 mL of epinephrine per total volume of 5-FU injected. | Intratumoral | — | — | 🌎 NA |
- Intratumoral injection with epinephrine into certain skin neoplasms (squamous cell carcinoma, melanoma, sarcoid): Epinephrine may result in white hair growth and can cause transient excitation, tachycardia, and shaking if absorbed systemically in sufficient quantities.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Fluorouracil (5-FU) is a pyrimidine analogue antineoplastic agent used in veterinary medicine to treat specific types of cancer.
- Dogs: Used systemically for mammary carcinoma (often as part of the FAC protocol alongside doxorubicin and cyclophosphamide), dermal squamous cell carcinoma, and gastrointestinal tract tumors.
- Horses: Used topically or via intralesional injection (often combined with epinephrine) to treat skin neoplasms such as squamous cell carcinoma, melanoma, and equine sarcoids.
CRITICAL SPECIES DIFFERENCE: 5-FU is strictly contraindicated in cats. Cats lack the necessary metabolic pathways to safely process the drug, leading to severe, rapidly progressive, and frequently fatal neurotoxicity even at microscopic doses (e.g., accidental ingestion of human topical creams).
Mechanism of action
Fluorouracil is a prodrug that acts as a cell-cycle phase-specific (S-phase) antimetabolite. It enters the cell and is converted into two primary active metabolites:
- FUMP (fluorouridine monophosphate) → Inhibits the enzyme thymidylate synthase, which blocks the synthesis of deoxythymidine triphosphate (dTTP). This severely disrupts DNA synthesis and repair.
- FUTP (fluorouridine triphosphate) → Falsely incorporates into RNA, disrupting RNA processing, function, and subsequent protein synthesis.
By halting both DNA and RNA functions, the drug induces apoptosis in rapidly dividing cancer cells.
Safety & warnings
Contraindications
- CATS (Do NOT use in any form, including topical)
- Patients with known hypersensitivity to the drug
- Patients in poor nutritional states
- Patients with depressed or reduced bone marrow function
- Patients with concurrent serious infections
- Pregnancy (Known teratogen - FDA Category D)
- Cats (strictly contraindicated due to fatal neurotoxicity)
- Patients with severe bone marrow suppression
- Patients with severe hepatic or renal impairment (unless dose is adjusted)
- Pregnancy and lactation
Adverse effects
- Dose-dependent myelosuppression (leukopenia, thrombocytopenia)
- Gastrointestinal toxicity (nausea, vomiting, hemorrhagic diarrhea, GI ulceration/sloughing, stomatitis)
- Neurotoxicity (ataxia, disorientation, seizures)
- Fatal neurotoxicity in cats (even with topical exposure)
- Anorexia
- Diarrhoea
- Leucopenia (nadir between 7 and 14 days)
- Anaemia
- Alopecia
- Hyperpigmentation
- Dermatitis
- Cerebellar ataxia
Precautions
Fluorouracil has a very narrow therapeutic index and should only be administered by clinicians experienced with cancer chemotherapeutic agents.
Feline Toxicity: Cats develop severe, potentially fatal neurotoxicity. It is contraindicated in cats in any form.
Reproductive Safety: 5-FU is a known teratogen. Pregnant women and pregnant veterinary staff should avoid handling this medication or the bodily fluids/waste of treated animals. If a nursing dam requires treatment, milk replacer should be used as the drug inhibits DNA/RNA synthesis.
Drug interactions
May increase the gastrointestinal toxic effects of 5-FU
Inhibits the metabolism of 5-FU, potentially increasing toxicity
Synergism in human oncology, but combination may be more toxic in small animals
Synergistic if administered before 5-FU; antagonistic if administered afterwards
Increases the cytotoxicity of 5-FU
Monitoring
- CBCs (nadirs usually occur between days 9-14 with recovery by day 30)
- Gastrointestinal adverse effects (vomiting, diarrhea, anorexia)
- Central nervous system adverse effects (ataxia, seizures)
- Liver enzymes (alkaline phosphatase, serum transaminase), serum bilirubin, and lactic dehydrogenase (may increase)
- Tumor response/Efficacy
- Complete Blood Count (CBC) to monitor for leucopenia and thrombocytopenia (nadir 7-14 days)
- Renal function parameters
- Hepatic function parameters
- Gastrointestinal signs (vomiting, diarrhea, stomatitis)
- Neurological signs
Pharmacokinetics
Half-life
Absorption
Administered systemically via the IV route.
Distribution
Primarily distributed into tumor cells, intestinal mucosa, liver, and bone marrow.
Metabolism
Converted via intracellular mechanisms to active metabolites (FUMP and FUTP); the majority of the drug is metabolized by the liver.
Elimination
A small amount (about 15% of dose) is excreted unchanged into the urine.
Overdose
Overdoses are extremely serious and potentially fatal.
- Dogs: The lowest reported toxic dose is 8.6 mg/kg (mild GI irritation/vomiting). Seizures and death have been reported at doses as low as 10.3 mg/kg, with survival rates potentially as low as 25%.
- Cats: Very small ingestions (such as licking human topical creams) can cause death.
Clinical Signs: Onset is rapid (30 minutes to 6 hours). Signs include acute nausea, vomiting, hemorrhagic diarrhea, abdominal pain, GI sloughing, ataxia, severe nonresponsive seizures, severe dose-dependent myelosuppression affecting all cell lines, metabolic acidosis, and multi-organ failure.
Treatment:
- Aggressive GI decontamination and protection if ingestion was very recent (though rapid onset may render this ineffective).
- Intensive supportive care: antiemetics, fluid support, pain control, and temperature regulation.
- Seizure control: Diazepam is often unrewarding; barbiturates or general anesthesia are frequently required.
- Broad-spectrum antibiotics to prevent secondary infections.
- Filgrastim (Neupogen®) can be considered to stimulate bone marrow stem cell proliferation in dogs.
- Intensive hematologic monitoring (CBCs every 3-4 days) for at least 3-4 weeks.
Available products
Formulations
- Injection solution
- Topical solution
- Injectable solution: 250 mg/vial, 500 mg/vial, 2500 mg/vial
- Topical cream: 5%
Human-labeled
- Fluorouracil Injection: 50 mg/mL in 10 mL, 20 mL, 50 mL, & 100 mL vials and 10 mL amps (Adrucil®; generic)
- Topical creams and solutions: 0.5% to 5% (used for actinic keratoses and superficial basal cell carcinomas)
- Efudix 5% cream
- Fluorouracil injectable solutions (various generics)
Regulatory status
Human-approved drug used under the cascade.
POM. Used under the prescribing cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store injection between 15-30°C; avoid freezing and exposure to light. Slight color changes in the solution can be ignored. If a precipitate forms, the solution can be heated to 60°C and shaken vigorously to redissolve the drug. Cool to body temperature before administering. If unsuccessful in redissolving the drug, it should not be used.
Client information
CRITICAL WARNING FOR CAT OWNERS: Human topical creams containing 5-FU (used for skin lesions) are highly toxic and frequently fatal to cats. Even a tiny lick or walking across a treated area and grooming can cause death. Keep all such medications strictly out of reach.
- Serious Side Effects: Understand that this is a potent chemotherapy drug. It can cause severe gastrointestinal upset, bone marrow suppression (increasing the risk of infection), and neurological signs.
- Monitoring: Strict adherence to follow-up appointments for bloodwork (CBCs) is mandatory to ensure your pet's white blood cell counts remain safe.
- Safety at Home: Because this drug is a known teratogen (can cause birth defects) and is excreted in bodily fluids, pregnant women, nursing mothers, and children should avoid handling the medication or the pet's waste (urine/feces) for several days post-treatment. Wear gloves when cleaning up accidents.
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.