レフルノミド
Leflunomide
N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide
別名: Arava · HW A 486 · RS 34821 · SU 101
VetSheet 獣医チームが監修更新日 2026年4月5日エビデンスに基づく獣医学リファレンス
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
動物種別用量
🌎 NA — North America🌍 EU — Europe
犬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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.
猫
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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.
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
概要
レフルノミドは疾患修飾性抗リウマチ薬（DMARD）であり、獣医療においてはステロイド節約型の強力な免疫抑制剤として適応外使用されます。主に犬の難治性免疫介在性疾患（免疫介在性溶血性貧血：IMHAなど）、全身性および皮膚反応性組織球症、臓器移植の拒絶反応抑制プロトコルなどに用いられます。
作用機序
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・警告
禁忌
- 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
有害事象
- 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.
医薬品相互作用
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
監視
- 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
薬物動態
半減期
吸収
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.
分布
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.
消失
Excreted in the urine and bile. The active metabolite can be detectable up to 2 years after discontinuation.
過剰投与
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.
製品
製剤
- Tablets
- 10 mg tablet
- 15 mg tablet
- 20 mg tablet
- 100 mg tablet
ヒト用医薬品
- Leflunomide Tablets: 10 mg & 20 mg (Arava®, generic)
- Arava 10 mg tablets
- Arava 15 mg tablets
- Arava 20 mg tablets
- Arava 100 mg tablets
規制ステータス
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
規制データなし: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
保管・安定性
Store tablets at room temperature (15-30°C) and protect from light.
飼主向け情報
- 実験的使用: 獣医療での使用は比較的実験的です。異常な症状（食欲低下、無気力、嘔吐など）が見られた場合は、すぐに獣医師に連絡してください。
- 安全上の注意: 本薬には催奇形性（胎児の先天異常を引き起こす可能性）があります。妊娠中または妊娠を計画している女性は、この薬に絶対に触れないでください。薬を扱う際は必ず手袋を着用し、錠剤を砕いたり割ったりしないでください。
- 費用: 治療費が高額になる場合がありますが、ジェネリック医薬品の普及により価格は下がってきています。
VetSheet医薬品リファレンスは獣医専門家の臨床意思決定支援を目的としており、専門的判断または製造業者の最新医薬品情報の代替にはなりません。