Chlorambucil
Chlorambucil is a nitrogen mustard derivative used primarily as an **antineoplastic** and **immunosuppressive** agent in veterinary medicine. * **Clinical Pearls:** It is highly favored in feline medicine for treating severe autoimmune diseases (e.g., inflammatory bowel disease, pemphigus foliaceus) and small cell (low-grade) gastrointestinal lymphoma because it is significantly less toxic and better tolerated in cats compared to other alkylating agents like cyclophosphamide or azathioprine. * It is also utilized in various neoplastic conditions including lymphocytic leukemia, multiple myeloma, polycythemia vera, and macroglobulinemia. * Due to its potential to cause myelosuppression, routine monitoring of complete blood counts (CBC) is essential during therapy.
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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.
วิธีการให้ยา
ข้อห้ามใช้
- Known hypersensitivity or resistance to the drug
- Pregnancy (potential teratogen)
อาการไม่พึงประสงค์
- 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)
อันตรกิริยาระหว่างยา
- 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
การติดตาม
- 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)
การได้รับยาเกินขนาด
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.
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