レフルノミド
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.
動物種別の用量
- 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.
- 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.
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
- 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
- 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
薬物相互作用
- 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
モニタリング
- 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
過量投与
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.
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。