레플루노마이드
Leflunomide
N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide
다른 이름: Arava · HW A 486 · RS 34821 · SU 101
VetSheet 수의사 팀 검수업데이트 2026년 4월 5일근거 기반 수의학 참고자료
용량은 수의사 전문가를 위한 임상 참고자료입니다. 반드시 최신 약물 정보 및 개별 환자에 따라 확인하시기 바랍니다.
동물 종별 용량
🌎 NA — North America🌍 EU — Europe
개
| 적응증 | 용량 | 경로 | 빈도 | 기간 | 지역 |
|---|---|---|---|---|---|
| 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.
고양이
| 적응증 | 용량 | 경로 | 빈도 | 기간 | 지역 |
|---|---|---|---|---|---|
| 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.
용량은 수의사 전문가를 위한 임상 참고자료입니다. 반드시 최신 약물 정보 및 개별 환자에 따라 확인하시기 바랍니다.
개요
레플루노마이드는 질병조절 항류마티스제(DMARD)로, 수의학에서는 스테로이드 사용을 줄일 수 있는 강력한 면역억제제로 오프라벨로 사용됩니다. 주로 개의 난치성 면역매개성 질환(면역매개성 용혈성 빈혈 등), 전신 및 피부 반응성 조직구증, 장기 이식 거부 반응 억제 프로토콜 등에 사용됩니다.
작용 기전
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.
안전성·주의사항
금기사항
- 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
부작용
- 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
주의
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.
약물 상호작용
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
모니터링
- 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
약동학
반감기
흡수
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.
분포
Highly bound to albumin (>99%).
대사
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.
배설
Excreted in the urine and bile. The active metabolite can be detectable up to 2 years after discontinuation.
과다투여
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.
제품
제형
- Tablets
- 10 mg tablet
- 15 mg tablet
- 20 mg tablet
- 100 mg tablet
인용의약품
- Leflunomide Tablets: 10 mg & 20 mg (Arava®, generic)
- Arava 10 mg tablets
- Arava 15 mg tablets
- Arava 20 mg tablets
- Arava 100 mg tablets
규제 현황
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
규제 데이터 없음: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
보관·안정성
Store tablets at room temperature (15-30°C) and protect from light.
보호자 정보
- 실험적 사용: 수의학 환자에게 사용하는 것은 비교적 실험적입니다. 식욕 감소, 무기력, 구토 등 비정상적인 반응이 관찰되면 즉시 수의사에게 연락하십시오.
- 안전 주의사항: 이 약물은 기형 유발 물질(선천적 결손증 유발 가능)로 알려져 있습니다. 임산부나 임신을 계획 중인 여성은 이 약을 절대 만져서는 안 됩니다. 약을 다룰 때는 항상 장갑을 착용하고, 알약을 부수거나 쪼개지 마십시오.
- 비용: 치료 비용이 매우 비쌀 수 있으나, 제네릭 의약품의 출시로 가격이 낮아지고 있습니다.
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