레플루노마이드

면역조절제

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.

동물 종별 용량

Cats

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 · Used in combination with methotrexate.

Dogs

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
Adjunctive immunosuppressive for immune-mediated hemolytic anemia · 4 mg/kg PO q24h · PO · q24h
Treatment of systemic and cutaneous reactive histiocytosis · 2-4 mg/kg PO once daily to attain trough levels of 20 micrograms/mL · PO · q24h
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 · In combination with human intravenous immunoglobulin (hIVIg). Target trough level approx 20 micrograms/mL.

용량은 면허 수의 전문가를 위한 임상 참고 자료입니다. 항상 최신 라벨과 개별 환자에 대해 확인하십시오.

투여 경로

금기

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

이상반응

Decreased appetite
Lethargy
Vomiting
Diarrhea
Lymphopenia
Anemia
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

약물 상호작용

Charcoal, Activated · Can increase elimination and decrease A77 1726 drug concentrations; used for rapid washout.
Cholestyramine · Can increase elimination and decrease A77 1726 drug concentrations; used for rapid washout.
Hepatotoxic Agents · Increased risk for hepatotoxicity when used concurrently.
Methotrexate · Increased risk of adverse effects and elevated ALT.
Phenytoin · Leflunomide can increase phenytoin levels.
Rifampin · Can increase A77 1726 peak levels.
Vaccines, Live Virus · Should be used with extreme caution, if at all, due to immunosuppression.
Warfarin · Leflunomide may increase INR.
Other immunosuppressants (e.g., cyclosporine, azathioprine) · Increased risk of severe immunosuppression and bone marrow toxicity · major
Live vaccines · Risk of disseminated infection due to immunosuppression · major

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)
Complete Blood Count (CBC)
Liver enzymes (ALT, AST, ALP)
Clinical signs of secondary infections
Gastrointestinal tolerance

과용량

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.

VetSheet 약물 레퍼런스는 면허 수의 전문가를 위한 임상 의사결정 보조 도구이며, 전문적 판단이나 제조사의 최신 라벨을 대신하지 않습니다.