來氟米特
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.
各物種劑量
- 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.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
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
- 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
藥物相互作用
- 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
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)
- Complete Blood Count (CBC)
- Liver enzymes (ALT, AST, ALP)
- Clinical signs of secondary infections
- Gastrointestinal tolerance
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.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。