Fluorouracil
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).
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- ALL · CONTRAINDICATED · ALL · Do NOT use in any form on cats
- All indications · DO NOT USE · PO/IM/IV/SC/topical · null · null · Strictly contraindicated. Causes potentially fatal neurotoxicity.
- 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 · Epinephrine may result in white hair growth and can cause transient excitation, tachycardia, and shaking if absorbed systemically in sufficient quantities.
- 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
- Systemic carcinomas · 150 mg/m2 · IV · once weekly OR once every 3 weeks when combined with carboplatin · 6 weeks (if used weekly) · Reduce dose by half in patients with liver, renal, or bone marrow impairment.
- Basal cell and squamous cell carcinoma · Apply to affected area · topical · q24h · As directed by oncologist · Wear gloves when applying. Prevent the dog from licking the area.
ขนาดยาเป็นข้อมูลอ้างอิงทางคลินิกสำหรับสัตวแพทย์ผู้มีใบอนุญาต โปรดตรวจสอบกับฉลากล่าสุดและผู้ป่วยแต่ละรายเสมอ
วิธีการให้ยา
ข้อห้ามใช้
- 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
อาการไม่พึงประสงค์
- 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
- Vomiting
- Stomatitis
- Diarrhoea
- Leucopenia (nadir between 7 and 14 days)
- Thrombocytopenia
- Anaemia
- Alopecia
- Hyperpigmentation
- Dermatitis
- Cerebellar ataxia
- Seizures
อันตรกิริยาระหว่างยา
- Leucovorin · May increase the gastrointestinal toxic effects of 5-FU
- Cimetidine · Inhibits the metabolism of 5-FU, potentially increasing toxicity · major
- Carboplatin · Synergism in human oncology, but combination may be more toxic in small animals · major
- Methotrexate · Synergistic if administered before 5-FU; antagonistic if administered afterwards · major
- Vincristine · Increases the cytotoxicity of 5-FU · major
การติดตาม
- 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
การได้รับยาเกินขนาด
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.
ข้อมูลอ้างอิงยาของ VetSheet มีไว้สำหรับสัตวแพทย์ผู้มีใบอนุญาตเพื่อช่วยในการตัดสินใจทางคลินิก ไม่ใช่สิ่งทดแทนการวินิจฉัยของผู้เชี่ยวชาญหรือฉลากล่าสุดของผู้ผลิต