クロラムブシル
クロラムブシルはナイトロジェンマスタード誘導体であり、獣医学において主に**抗悪性腫瘍薬**および**免疫抑制剤**として使用されます。 * **臨床のポイント:** 猫の重度自己免疫疾患（炎症性腸疾患、落葉状天疱瘡など）や小細胞性（低悪性度）消化器型リンパ腫の治療において、シクロホスファミドやアザチオプリンなどの他のアルキル化剤と比較して毒性が著しく低く、忍容性が高いため、猫の医療で非常に好まれています。 * また、リンパ性白血病、多発性骨髄腫、真性多血症、マクログロブリン血症などの様々な腫瘍性疾患にも使用されます。 * 骨髄抑制を引き起こす可能性があるため、治療中は全血球計算（CBC）の定期的なモニタリングが不可欠です。
作用機序: 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.
動物種別の用量
- 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.
- 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.
- 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.
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
- Known hypersensitivity or resistance to the drug
- Pregnancy (potential teratogen)
有害事象
- 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)
薬物相互作用
- 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
モニタリング
- 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)
過量投与
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 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。