フルオロウラシル
フルオロウラシル (5-FU) は、獣医学において特定の種類の癌の治療に使用されるピリミジンアナログの抗悪性腫瘍薬です。 * **犬**: 乳癌（通常、ドキソルビシンおよびシクロホスファミドと併用するFACプロトコルの一部として）、皮膚扁平上皮癌、および消化管腫瘍に対して全身的に使用されます。 * **馬**: 扁平上皮癌、悪性黒色腫、馬サルコイドなどの皮膚腫瘍を治療するために、局所または病変内注射（多くの場合エピネフリンと併用）として使用されます。 > **重大な動物種間の違い**: 5-FUは**猫には絶対禁忌**です。猫にはこの薬物を安全に処理するために必要な代謝経路が欠如しており、ごく微量（人間用の外用クリームの誤飲など）であっても、重度で急速に進行し、多くの場合致命的な神経毒性を引き起こします。
作用機序: 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.
動物種別の用量
- 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.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- 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
有害事象
- 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
薬物相互作用
- 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
モニタリング
- 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
過量投与
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 の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。