來氟米特
Leflunomide
N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide
別名: Arava · HW A 486 · RS 34821 · SU 101
由 VetSheet 獸醫團隊審訂更新於 2026年4月5日本內容以實證獸醫文獻為本
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
各物種劑量
🌎 NA — North America🌍 EU — Europe
狗
| 適應症 | 劑量 | 途徑 | 頻次 | 療程 | 地區 |
|---|---|---|---|---|---|
| Immunosuppressive as part of a protocol (with cyclosporine) following organ transplant | 4-6 mg/kg PO q24h and then to maintain trough plasma levels of 20 micrograms/mL | PO | q24h | — | 🌎 NA |
| Adjunctive immunosuppressive for immune-mediated hemolytic anemia | 4 mg/kg PO q24h | PO | q24h | — | 🌎 NA |
| Treatment of systemic and cutaneous reactive histiocytosis | 2-4 mg/kg PO once daily to attain trough levels of 20 micrograms/mL | PO | q24h | — | 🌎 NA |
| Treatment of Evans' Syndrome in a diabetic dog | 2 mg/kg PO q12h | PO | q12h | Decreased by 25% every 4 weeks for first 4 months, then every 8 weeks | 🌎 NA |
- Treatment of Evans' Syndrome in a diabetic dog: In combination with human intravenous immunoglobulin (hIVIg). Target trough level approx 20 micrograms/mL.
貓
| 適應症 | 劑量 | 途徑 | 頻次 | 療程 | 地區 |
|---|---|---|---|---|---|
| Rheumatoid arthritis | Initially, leflunomide at 10 mg (total dose) PO once daily and methotrexate at 2.5 mg (total dose) PO three times on one day per week. When significant improvement occurs, reduce doses of leflunomide to 10 mg PO twice weekly and methotrexate to 2.5 mg PO once weekly. | PO | q24h initially, then twice weekly | — | 🌎 NA |
- Rheumatoid arthritis: Used in combination with methotrexate.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
概覽
來氟米特（Leflunomide）是一種疾病修飾抗風濕藥物（DMARD），在獸醫學中作為標籤外使用的強效、可減少類固醇用量的免疫抑制劑。它主要用於治療犬隻難治性免疫介導疾病，如免疫介導性溶血性貧血（IMHA）、全身性和皮膚反應性組織細胞增生症，以及作為器官移植排斥反應的輔助治療。
作用機制
Leflunomide is a prodrug that is rapidly converted in the intestinal mucosa and liver to its active metabolite, teriflunomide (A77 1726 or M1).
- Mechanism: Teriflunomide reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH).
- Pathway: Inhibition of DHODH → prevents the formation of ribonucleotide uridine monophosphate (rUMP) → decreases de novo pyrimidine synthesis → decreases DNA and RNA synthesis.
- Result: This induces G1 cell cycle arrest, profoundly inhibiting the proliferation of rapidly dividing autoimmune T-cells and the production of autoantibodies by B-cells.
安全性與警告
禁忌症
- Pregnancy (Category X teratogen)
- Hypersensitivity to leflunomide
- Pre-existing immunodeficiency
- Significant renal impairment
- Pregnancy and lactation
- Pre-existing severe bone marrow suppression
- Severe hepatic impairment
- Active severe infections
不良反應
- Decreased appetite
- Lethargy
- Lymphopenia
- Alopecia
- Rash
- Hepatotoxicity
- Severe dermatologic reactions (Toxic Epidermal Necrolysis, Stevens-Johnson syndrome - reported in humans)
- Gastrointestinal upset (vomiting, diarrhea, anorexia)
- Bone marrow suppression (leukopenia, anemia, thrombocytopenia)
- Unexplained bleeding
注意事項
Teratogenicity Warning: Leflunomide is an FDA Category X teratogen. It must not be used in pregnant animals, and pregnant women should not handle this medication.
Prolonged Half-Life: The active metabolite (A77 1726) can persist in the body for up to 2 years after discontinuation. If severe toxicity occurs, a washout procedure using cholestyramine or activated charcoal is required.
Use with extreme caution in patients with hepatic disease, renal impairment, or pre-existing immunodeficiency.
藥物相互作用
Can increase elimination and decrease A77 1726 drug concentrations; used for rapid washout.
Can increase elimination and decrease A77 1726 drug concentrations; used for rapid washout.
Increased risk for hepatotoxicity when used concurrently.
Increased risk of adverse effects and elevated ALT.
Leflunomide can increase phenytoin levels.
Can increase A77 1726 peak levels.
Should be used with extreme caution, if at all, due to immunosuppression.
Leflunomide may increase INR.
Increased risk of severe immunosuppression and bone marrow toxicity
Risk of disseminated infection due to immunosuppression
監測
- Complete Blood Count (CBC) for hematologic toxicity (lymphopenia, anemia)
- Liver enzymes (ALT, AST, ALP) for hepatotoxicity
- Trough levels of A77 1726 (Target is 20 micrograms/mL)
- Clinical signs of secondary infections
- Gastrointestinal tolerance
藥物動力學
半衰期
吸收
Rapidly converted to active metabolite A77 1726 (M1) in the GI mucosa and liver. Peak levels occur 6-12 hours post-dose. Food does not affect bioavailability.
分佈
Highly bound to albumin (>99%).
代謝
Converted to A77 1726 in GI mucosa/liver. Further degraded in the liver as glucuronides and an oxalinic acid compound. Conversion to toxic metabolites is reported to be slower in cats than in dogs.
排除
Excreted in the urine and bile. The active metabolite can be detectable up to 2 years after discontinuation.
過量
Acute toxicologic studies in mice and rats demonstrate minimally toxic doses of 200 mg/kg and 100 mg/kg, respectively.
Washout Protocol: Because of the extremely long half-life of the active metabolite, cholestyramine or activated charcoal administration is highly recommended to accelerate elimination in cases of overdose or severe toxicity. Contact an animal poison control center for specific washout protocols.
可用產品
劑型
- Tablets
- 10 mg tablet
- 15 mg tablet
- 20 mg tablet
- 100 mg tablet
人用標示
- Leflunomide Tablets: 10 mg & 20 mg (Arava®, generic)
- Arava 10 mg tablets
- Arava 15 mg tablets
- Arava 20 mg tablets
- Arava 100 mg tablets
各地核准狀態
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
暫無法規資料: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
儲存與穩定性
Store tablets at room temperature (15-30°C) and protect from light.
飼主須知
- 試驗性用藥：本藥物在獸醫臨床上相對屬於試驗性用藥；若發現寵物有任何異常反應（如食慾不振、嗜睡、嘔吐），請立即聯繫獸醫師。
- 安全警告：本藥物具有致畸胎性（可能導致出生缺陷）。孕婦或計畫懷孕的婦女絕對不可接觸此藥物。處理藥物時請務必戴上手套，且切勿壓碎或剝半藥錠。
- 費用：治療費用可能相當昂貴，但隨著學名藥的普及，價格已逐漸降低。
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