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.
Mechanism: Chlorambucil is a **cell-cycle nonspecific alkylating agent**. * **Mechanism:** It works by forming highly reactive carbonium ions that cross-link with cellular **DNA** โ prevents DNA transcription and replication โ disrupts nucleic acid function โ ultimately leads to cell death (apoptosis). * Its immunosuppressive effects are secondary to its cytotoxic action on rapidly dividing lymphoid cells.
Dosing by species
- Adjunctive therapy for glomerulonephritis ยท 0.1-0.2 mg/kg PO once daily or every other day ยท PO ยท q24h or q48h
- Canine lymphoma (first level treatment when combination chemo is declined) ยท 6-8 mg/m2 (NOT mg/kg) PO every other day ยท PO ยท q48h ยท 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 ยท 2-4 mg/m2 (NOT mg/kg) PO q24-48h ยท PO ยท q24-48h
- Pemphigus complex ยท 0.2 mg/kg q24-48h ยท PO ยท q24-48h ยท With Prednisone 2-4 mg/kg PO divided q12h
- Pemphigus complex ยท 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. ยท PO ยท q24h initially, then q48h ยท Several weeks ยท Used in combination with corticosteroids. Alternately decrease chlorambucil and corticosteroids until lowest possible dose is attained.
- Adjunctive treatment of inflammatory bowel disease ยท 1.5 mg/m2 (NOT mg/kg) PO every other day ยท PO ยท q48h
- Chronic lymphocytic leukaemia ยท 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 ยท PO ยท q24h or q1-2wk ยท Until remission, then maintenance ยท Give with food. Often used with prednisolone 40 mg/m2 p.o. q24h for 7 days then 20 mg/m2 q48h.
- Lymphoma ยท 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 ยท PO ยท q2wk (15-20 mg/m2) or q24-48h (2-6 mg/m2) ยท Protocol dependent ยท Give with food.
Routes of administration
Contraindications
- Known hypersensitivity or resistance to the drug
- Pregnancy (potential teratogen)
Adverse effects
- 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)
Drug interactions
- Chloramphenicol ยท Additive bone marrow depression
- Flucytosine ยท Additive bone marrow depression
- Amphotericin B ยท Additive bone marrow depression
- Colchicine ยท Additive bone marrow depression
- Azathioprine ยท Increased risk of infection and immunosuppression
- Cyclophosphamide ยท Increased risk of infection and immunosuppression
- Cyclosporine ยท Increased risk of infection and immunosuppression
- Corticosteroids ยท Increased risk of infection and immunosuppression
- Hepatic cytochrome P450 stimulators ยท Increases cytotoxic effects of chlorambucil ยท major
- Prednisolone ยท Synergistic effect in the management of lymphoid neoplasia ยท minor
Monitoring
- 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)
Overdose
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 drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.