Leflunomide
Leflunomide is a disease-modifying antirheumatic drug (DMARD) used off-label in veterinary medicine as a potent, steroid-sparing immunosuppressant. * **Clinical Uses**: It is primarily utilized in dogs for refractory immune-mediated conditions such as immune-mediated hemolytic anemia (IMHA), immune-mediated polyarthritis (IMPA), systemic and cutaneous reactive histiocytosis, and granulomatous meningoencephalitis (GME). It is also used in transplant rejection protocols. * **Feline Use**: Occasionally used in combination with methotrexate for feline rheumatoid arthritis. * **Clinical Pearl**: Because leflunomide targets *de novo* pyrimidine synthesis (which activated lymphocytes heavily rely upon), it provides a targeted immunosuppressive effect. However, its active metabolite has an exceptionally long half-life, meaning toxicity can persist long after the drug is discontinued.
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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.
ขนาดยาเป็นข้อมูลอ้างอิงทางคลินิกสำหรับสัตวแพทย์ผู้มีใบอนุญาต โปรดตรวจสอบกับฉลากล่าสุดและผู้ป่วยแต่ละรายเสมอ
วิธีการให้ยา
ข้อห้ามใช้
- 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
อาการไม่พึงประสงค์
- 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
อันตรกิริยาระหว่างยา
- 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
การติดตาม
- 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
การได้รับยาเกินขนาด
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.
ข้อมูลอ้างอิงยาของ VetSheet มีไว้สำหรับสัตวแพทย์ผู้มีใบอนุญาตเพื่อช่วยในการตัดสินใจทางคลินิก ไม่ใช่สิ่งทดแทนการวินิจฉัยของผู้เชี่ยวชาญหรือฉลากล่าสุดของผู้ผลิต