Chlorambucil
4-[bis(2-chloroethyl)amino]benzenebutanoic acid
Also known as: Leukeran · Chloraminophene · Linfolysin · CB-1348 · NSC-3088 · WR-139013 · chlorambucilum · chlorbutinum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive therapy for glomerulonephritis | 0.1-0.2 mg/kg PO once daily or every other day | PO | q24h or q48h | — | 🌎 NA |
| Canine lymphoma (first level treatment when combination chemo is declined) | 6-8 mg/m2 (NOT mg/kg) PO every other day | PO | q48h | — | 🌎 NA |
| Lymphoproliferative disease; macroglobulinemia | 2-4 mg/m2 (NOT mg/kg) PO q24-48h | PO | q24-48h | — | 🌎 NA |
| Pemphigus complex | 0.2 mg/kg q24-48h | PO | q24-48h | — | 🌎 NA |
| 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 | 🌎 NA |
| Adjunctive treatment of inflammatory bowel disease | 1.5 mg/m2 (NOT mg/kg) PO every other day | PO | q48h | — | 🌎 NA |
| 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 | 🌍 EU |
| 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 | 🌍 EU |
| 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 | 🌍 EU |
| 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 | 🌍 EU |
| Metronomic chemotherapy | 4 mg/m2 | PO | q24h | Ongoing | 🌍 EU |
- Canine lymphoma (first level treatment when combination chemo is declined): Used in combination with Prednisone 40 mg/m2 PO daily for 7 days then every other day. Perform CBC every 2-3 weeks.
- Pemphigus complex: With Prednisone 2-4 mg/kg PO divided q12h
- Pemphigus complex: Used in combination with corticosteroids. Alternately decrease chlorambucil and corticosteroids until lowest possible dose is attained.
- Chronic lymphocytic leukaemia: Give with food. Often used with prednisolone 40 mg/m2 p.o. q24h for 7 days then 20 mg/m2 q48h.
- Lymphoma: Give with food.
- Pemphigus complex: Give with food. Used in combination with corticosteroids.
- Protein-losing enteropathy and other immune-mediated diseases: Give with food.
- Metronomic chemotherapy: Give with food.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| 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 | 🌎 NA |
| Refractory or severe IBD (Cats < 4 kg) | 2 mg (total dose) q72 hours (every 3rd day) | PO | q72h | — | 🌎 NA |
| 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 | — | 🌎 NA |
| 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 | — | 🌎 NA |
| 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 | — | 🌎 NA |
| 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 | — | 🌎 NA |
| Pemphigus complex or other immune-mediated dermatoses | 2 mg (total dose per cat) every 48 hours | PO | q48h | — | 🌎 NA |
| Generalized pemphigus foliaceous | 0.1-0.2 mg/kg PO q24-48h | PO | q24-48h | — | 🌎 NA |
| Idiopathic dermatitis | 0.2 mg/kg PO q24-48h | PO | q24-48h | — | 🌎 NA |
| Adjunctive treatment of FIP | 20 mg/m2 (NOT mg/kg) every 2-3 weeks | PO | q2-3w | — | 🌎 NA |
| Lymphocytic leukemia | 6 mg/m2 (2 mg/5.3 kg cat) PO every other day | PO | q48h | — | 🌎 NA |
| Immune-mediated disease | >4 kg: 2 mg (total dose); <4 kg: 2 mg (total dose) | PO | q48h (>4 kg) or q72h (<4 kg) | 2-4 weeks, then tapered to lowest effective dose | 🌍 EU |
| Chronic lymphocytic leukaemia | 2 mg/m2 OR 20 mg/m2 | PO | q48h (2 mg/m2) or q14d (20 mg/m2) | Ongoing | 🌍 EU |
| Low grade/small cell lymphoma | 20 mg/m2 | PO | q14d | Ongoing | 🌍 EU |
| Substitute for cyclophosphamide in CHOP protocol | 1.4 mg/kg | PO | Once | Single dose | 🌍 EU |
| Feline pemphigus foliaceus or severe feline eosinophilic granuloma complex | 0.1-0.2 mg/kg initially until marked improvement, then alternate-day dosing | PO | q24h initially, then q48h | Often for several weeks | 🌍 EU |
- Refractory or severe IBD (Cats > 4 kg): Second choice after corticosteroids
- Severe IBD or intestinal lymphoma: In combination with prednisolone. Alternatively, may dose at 2 mg (total dose) per cat every 4 days indefinitely.
- Lymphocytic-plasmacytic enteritis (LPE) - Method 1: Administer with prednisolone. Common for patients to develop anemia.
- Lymphocytic-plasmacytic enteritis (LPE) - Method 2: Slowly taper to lowest effective dose after 4-6 weeks.
- Pemphigus complex or other immune-mediated dermatoses: May be used in combination with or as an alternative to steroids.
- Generalized pemphigus foliaceous: Add if poor response to prednisolone alone.
- Idiopathic dermatitis: Closely monitor during treatment.
- Adjunctive treatment of FIP: With Prednisolone 4 mg/kg PO once daily
- Lymphocytic leukemia: With prednisolone 5 mg/cat/day. Supplemental cobalamin and folate/B-complex vitamins should also be given.
- Immune-mediated disease: Give with food.
- Chronic lymphocytic leukaemia: Give with food. With or without prednisolone.
- Low grade/small cell lymphoma: Give with food. Used with prednisolone.
- Substitute for cyclophosphamide in CHOP protocol: Give with food.
- Feline pemphigus foliaceus or severe feline eosinophilic granuloma complex: Give with food. Used in combination with corticosteroids.
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive therapy in treating lymphoma using the LAP protocol | 20 mg/m2 (NOT mg/kg) PO every 2 weeks | PO | q2w | — | 🌎 NA |
- Adjunctive therapy in treating lymphoma using the LAP protocol: Alternating with cytosine arabinoside and Prednisone 1.1-2.2 mg/kg PO every other day.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
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 of action
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.
Safety & warnings
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)
Precautions
Important Warnings:
- Myelosuppression: Use with extreme caution in patients with preexisting bone marrow depression or active infections.
- Toxicity: Higher dosages increase the likelihood of toxicity. Nadirs usually occur within 7-14 days of starting therapy.
- Reproductive Safety: Potential teratogen. Avoid during pregnancy unless benefits clearly outweigh risks. Documented to cause irreversible infertility in male humans.
- Handling: Caregivers should wear gloves when handling this medication to prevent accidental exposure.
Drug interactions
Additive bone marrow depression
Additive bone marrow depression
Additive bone marrow depression
Additive bone marrow depression
Increased risk of infection and immunosuppression
Increased risk of infection and immunosuppression
Increased risk of infection and immunosuppression
Increased risk of infection and immunosuppression
Increases cytotoxic effects of chlorambucil
Synergistic effect in the management of lymphoid neoplasia
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)
Pharmacokinetics
Absorption
Rapidly and nearly completely absorbed after oral administration; peak levels occur in about one hour.
Distribution
Highly bound to plasma proteins. Crosses the placenta. Unknown if it crosses the blood-brain barrier, but neurological side effects have been reported.
Metabolism
Extensively metabolized in the liver, primarily to phenylacetic acid mustard, which is active.
Elimination
Phenylacetic acid mustard is further metabolized to other metabolites that are excreted in the urine.
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.
Available products
Formulations
- tablets
- oral suspension (compounded)
Human-labeled
- Chlorambucil Oral Tablets (film-coated): 2 mg; Leukeran® (GlaxoSmithKline); (Rx)
Regulatory status
POM (Prescription Only Medicine). Handled under strict cytotoxic drug regulations.
POM. Handled under strict cytotoxic drug regulations.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Tablets should be stored in light-resistant, well-closed containers under refrigeration (2-8°C; 36-46°F). Tablets can be stored at a maximum of 30°C (86°F) up to one week. Compounded oral suspensions (2 mg/mL) retain 90% potency for 7 days at 5°C; room temperature storage causes rapid decomposition.
Client information
Important Information for Pet Owners
- Administration: Give this medication exactly as directed by your veterinarian. Do not change the dose or stop abruptly without consulting your vet.
- Safe Handling: Because this is a chemotherapy drug, wear gloves when handling the tablets or suspension. Wash your hands thoroughly afterward. Pregnant women should avoid handling this medication entirely.
- What to Watch For: Immediately report any signs of toxicity to your veterinarian. This includes abnormal bleeding, unexplained bruising, blood in urine or stool, severe lethargy, signs of infection (like fever), or shortness of breath.
- Monitoring: Your pet will need regular blood tests to ensure the drug is not suppressing their bone marrow too much.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.