氟尿嘧啶
氟尿嘧啶 (5-FU) 是一種嘧啶類似物抗腫瘤藥物，在獸醫學中用於治療特定類型的癌症。 * **犬**：全身性用於乳腺癌（通常作為 FAC 療程的一部分，與阿黴素和環磷醯胺併用）、皮膚鱗狀細胞癌和胃腸道腫瘤。 * **馬**：局部或病灶內注射（通常與腎上腺素結合使用）以治療皮膚腫瘤，如鱗狀細胞癌、黑色素瘤和馬類肉瘤。 > **關鍵物種差異**：5-FU **絕對禁用於貓**。貓缺乏安全代謝該藥物所需的代謝途徑，即使是極微量（例如意外攝入人類局部藥膏）也會導致嚴重、快速惡化且通常致命的神經毒性。
作用機制: 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.
各物種劑量
- 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.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- 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
不良反應
- 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
藥物相互作用
- 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
監測
- 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
過量
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.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。