苯丁酸氮芥
免疫抑制劑 / 抗腫瘤藥
苯丁酸氮芥是一種氮芥衍生物，在獸醫學中主要用作**抗腫瘤**和**免疫抑制**劑。 * **臨床要點：** 在貓科醫學中備受青睞，用於治療嚴重的自體免疫疾病（如炎症性腸病、落葉型天皰瘡）和小細胞（低惡性度）胃腸道淋巴瘤，因為與環磷醯胺或硫唑嘌呤等其他烷化劑相比，它對貓的毒性顯著較低且耐受性更好。 * 它也可用於各種腫瘤疾病，包括淋巴性白血病、多發性骨髓瘤、真性紅血球增多症和巨球蛋白血症。 * 由於其可能引起骨髓抑制，治療期間必須常規監測全血球計數 (CBC)。
作用機制: Chlorambucil is a **cell-cycle nonspecific alkylating agent**. * **Mechanism:** It works by forming highly reactive carbonium ions that cross-link with cellular **DNA** → prevents DNA transcription and replication → disrupts nucleic acid function → ultimately leads to cell death (apoptosis). * Its immunosuppressive effects are secondary to its cytotoxic action on rapidly dividing lymphoid cells.
各物種劑量
Dogs
- Adjunctive therapy for glomerulonephritis · 0.1-0.2 mg/kg PO once daily or every other day · PO · q24h or q48h
- Canine lymphoma (first level treatment when combination chemo is declined) · 6-8 mg/m2 (NOT mg/kg) PO every other day · PO · q48h · Used in combination with Prednisone 40 mg/m2 PO daily for 7 days then every other day. Perform CBC every 2-3 weeks.
- Lymphoproliferative disease; macroglobulinemia · 2-4 mg/m2 (NOT mg/kg) PO q24-48h · PO · q24-48h
- Pemphigus complex · 0.2 mg/kg q24-48h · PO · q24-48h · With Prednisone 2-4 mg/kg PO divided q12h
- Pemphigus complex · 0.1-0.2 mg/kg once daily initially until marked improvement (or 75% improvement) of clinical signs (may require 4-8 weeks). Then alternate day dosing is begun and maintained for several weeks. · PO · q24h initially, then q48h · Several weeks · Used in combination with corticosteroids. Alternately decrease chlorambucil and corticosteroids until lowest possible dose is attained.
- Adjunctive treatment of inflammatory bowel disease · 1.5 mg/m2 (NOT mg/kg) PO every other day · PO · q48h
- Chronic lymphocytic leukaemia · 2-6 mg/m2 initially until remission achieved, then at reduced dosage/frequency; OR 0.2 mg/kg for 7 days then 0.1 mg/kg for maintenance; OR 20 mg/m2 every 1-2 weeks · PO · q24h or q1-2wk · Until remission, then maintenance · Give with food. Often used with prednisolone 40 mg/m2 p.o. q24h for 7 days then 20 mg/m2 q48h.
- Lymphoma · 15-20 mg/m2 with prednisolone; OR 2-6 mg/m2; OR 1.4 mg/kg as single dose substitute for cyclophosphamide in CHOP-type protocols · PO · q2wk (15-20 mg/m2) or q24-48h (2-6 mg/m2) · Protocol dependent · Give with food.
- Pemphigus complex · 0.1-0.2 mg/kg initially until marked improvement, then alternate-day dosing · PO · q24h initially, then q48h · Often for several weeks · Give with food. Used in combination with corticosteroids.
- Protein-losing enteropathy and other immune-mediated diseases · 2-6 mg/m2 until clinical remission, then tapered to the minimum effective dose · PO · q24h · Until remission, then tapered · Give with food.
- Metronomic chemotherapy · 4 mg/m2 · PO · q24h · Ongoing · Give with food.
Cats
- Refractory or severe IBD (Cats > 4 kg) · 2 mg (total dose) PO q48 hours (every other day) for 2-4 weeks then tapered to the lowest effective dose (2 mg per cat q72-96 hours; every 3rd to 4th day) · PO · q48h initially, then q72-96h · Indefinite · Second choice after corticosteroids
- Refractory or severe IBD (Cats < 4 kg) · 2 mg (total dose) q72 hours (every 3rd day) · PO · q72h
- Severe IBD or intestinal lymphoma · 15 mg/m2 (NOT mg/kg) PO once per day for 4 consecutive days, repeated every 3 weeks · PO · q24h for 4 days, repeat q3w · In combination with prednisolone. Alternatively, may dose at 2 mg (total dose) per cat every 4 days indefinitely.
- Lymphocytic-plasmacytic enteritis (LPE) - Method 1 · Initial dose is 2 mg/m2 (NOT mg/kg) PO for 4-7 days, then decreased to 1 mg/m2 (NOT mg/kg) for 7 days. If clinical signs are lessening, continue daily dosing but only every other week · PO · Variable · Administer with prednisolone. Common for patients to develop anemia.
- Lymphocytic-plasmacytic enteritis (LPE) - Method 2 · Large cats (>7 lb.) 2 mg PO twice weekly; smaller cats (<7 lb) 1 mg PO twice weekly · PO · Twice weekly · Slowly taper to lowest effective dose after 4-6 weeks.
- Severe IBD / Lymphoma (Alternative to prednisolone) · For cats < 2 kg: 2 mg (total dose) PO once weekly. For cats > 2 kg: 2 mg (total dose) PO once every 4 days. · PO · Once weekly or q4d
- Pemphigus complex or other immune-mediated dermatoses · 2 mg (total dose per cat) every 48 hours · PO · q48h · May be used in combination with or as an alternative to steroids.
- Generalized pemphigus foliaceous · 0.1-0.2 mg/kg PO q24-48h · PO · q24-48h · Add if poor response to prednisolone alone.
Horses
- Adjunctive therapy in treating lymphoma using the LAP protocol · 20 mg/m2 (NOT mg/kg) PO every 2 weeks · PO · q2w · Alternating with cytosine arabinoside and Prednisone 1.1-2.2 mg/kg PO every other day.
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
PO
禁忌症
- Known hypersensitivity or resistance to the drug
- Pregnancy (potential teratogen)
不良反應
- Myelosuppression (anemia, leukopenia, thrombocytopenia)
- Gastrointestinal toxicity (vomiting, diarrhea)
- Alopecia and delayed hair regrowth (especially in Poodles and Kerry Blue Terriers)
- Neurotoxicity (rare; facial twitching, myoclonus, agitation, seizures)
藥物相互作用
- Chloramphenicol · Additive bone marrow depression
- Flucytosine · Additive bone marrow depression
- Amphotericin B · Additive bone marrow depression
- Colchicine · Additive bone marrow depression
- Azathioprine · Increased risk of infection and immunosuppression
- Cyclophosphamide · Increased risk of infection and immunosuppression
- Cyclosporine · Increased risk of infection and immunosuppression
- Corticosteroids · Increased risk of infection and immunosuppression
- Hepatic cytochrome P450 stimulators · Increases cytotoxic effects of chlorambucil · major
- Prednisolone · Synergistic effect in the management of lymphoid neoplasia · minor
監測
- Clinical efficacy
- CBC and Platelets (once weekly or every other week initially; once stable, monthly or every 3-6 months)
- Uric acid levels (if warranted)
- Liver enzymes (if warranted)
過量
The oral LD50 in mice is 123 mg/kg. In humans, acute overdoses up to 5 mg/kg resulted in **neurologic toxicity (seizures)** and **pancytopenia** (nadirs at 1-6 weeks post ingestion). * **Treatment:** Consists of gut emptying when appropriate (beware of rapidly changing neurologic status if inducing vomiting). * **Monitoring:** CBCs several times a week for several weeks should be performed. Blood component therapy may be necessary.
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。