Azathioprine
Azathioprine is a thiopurine immunosuppressant used mainly in dogs with immune-mediated disease. It is often combined with a glucocorticoid as part of a longer-term strategy to suppress inappropriate immune activity and, where possible, reduce reliance on a single drug. Its onset is delayed, so it is not an immediate rescue treatment for rapidly progressive disease.
Veterinary use includes immune-mediated hemolytic anemia, selected immune-mediated skin disease and some inflammatory enteropathies. Cats are particularly susceptible to severe toxicity, and occasional equine reports do not establish the same evidence base as canine use.
Group
Thiopurine immunosuppressant
Mechanism of Action
Azathioprine is converted to 6-mercaptopurine and then through several competing pathways to active thiopurine metabolites. These interfere with purine metabolism and nucleic-acid synthesis; thioguanine nucleotides can be incorporated into cellular nucleic acids and alter proliferative and immune signaling processes.
Activated lymphocytes are particularly vulnerable because mounting an immune response requires sustained proliferation and nucleotide supply. Inhibition of T- and B-cell activation and expansion reduces cell-mediated and antibody-associated immune responses. The clinical effect is delayed because existing inflammatory activity does not disappear as soon as a dose is given.
Metabolic pathways also generate inactive or potentially hepatotoxic products, while exposure of other proliferating tissues can suppress bone marrow. Species and individual differences in thiopurine metabolism therefore affect toxicity as well as efficacy, explaining why canine experience cannot be safely extrapolated to cats.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Immune-mediated disease — Initial | 2 mg/kg | PO | Every 24 h | Reduce to the maintenance schedule according to response and laboratory monitoring. |
| Immune-mediated disease — Maintenance | 0.5–1 mg/kg | PO | Every 48 h | |
| Immune-mediated disease – prednisolone combination | 1.5 mg/kg | PO | Every 48 h | Higher alternative described with prednisolone; monitor marrow and liver. |
| Inflammatory bowel disease – staged course — Initial | 2 mg/kg | PO | Every 24 h | Up to 14 days |
| Inflammatory bowel disease – staged course — Maintenance | 2 mg/kg | PO | Every 48 h | Up to 28 days; 2–4 weeks after initial daily phase, then reduce to 1 mg/kg every 48 hours. |
| Inflammatory bowel disease – staged course — Maintenance | 1 mg/kg | PO | Every 48 h | Later maintenance after the preceding phase; benefit may take 2–6 weeks. |
| Myasthenia gravis – response-guided course — Initial | 1 mg/kg | PO | Every 24 h | Up to 14 days; CBC every 1–2 weeks. Increase only if neutrophils and platelets remain normal. |
| Myasthenia gravis – response-guided course — Maintenance | 2 mg/kg | PO | Every 24 h | After 2 weeks if CBC permits. Stop if WBC below 4000/µL or neutrophils below 1000/µL. Recheck AChR antibodies every 4–6 weeks; taper to alternate days when clinical and antibody remission occur. |
| Lymphoplasmacytic enteritis adjunct — Initial | 2 mg/kg | PO | Every 24 h | Up to 5 days; Then use on alternate days to prednisolone. |
| Lymphoplasmacytic enteritis adjunct — Maintenance | 2 mg/kg | PO | Every 48 h | After 5 daily doses; prednisolone on the other days. |
| Severe immune-mediated hemolytic anemia | 2.2 mg/kg | PO | Every 24 h | A described prednisone partner starts 2.2 mg/kg PO every 12 hours until PCV 25–30%, then tapers by about 25% every 2–3 weeks to 0.5 mg/kg every 48 hours. Do not apply this taper automatically to azathioprine. |
| Acute IMHA adjunct – alternative | 1–2 mg/kg | PO | Every 24 h | Used with glucocorticoids; monitor marrow and liver. |
| Severe refractory inflammatory bowel disease | 2.2 mg/kg | PO | Every 24 h | Clinical improvement may take 3–5 weeks. |
| Ocular fibrous histiocytoma adjunct — Initial | 2 mg/kg | PO | Every 24 h | Up to 14 days; Reevaluate after 2 weeks. |
| Ocular fibrous histiocytoma adjunct — Maintenance | 1 mg/kg | PO | Every 48 h | Up to 14 days; Second 2-week phase. |
| Ocular fibrous histiocytoma adjunct — Maintenance | 1 mg/kg | PO | Every 168 h | Final phase for 1 month. |
| Renal allograft rejection prevention | 1–5 mg/kg | PO | Every 48 h | MHC-matched renal allograft protocol with cyclosporine. |
| Perianal fistula – response-guided course — Initial | 2 mg/kg | PO | Every 24 h | Switch phase on improvement or WBC below 5000/µL, neutrophils below 3500/µL or platelets below 160000/µL; hematologic decline requires clinical reassessment. |
| Perianal fistula – response-guided course — Maintenance | 2 mg/kg | PO | Every 48 h | Up to 84 days; Continue 12 weeks only without myelosuppression; then reduce to 1 mg/kg every 48 hours. |
| Perianal fistula – response-guided course — Maintenance | 1 mg/kg | PO | Every 48 h | Final phase; planned total treatment 12 months. Initial partner prednisone is 2 mg/kg daily for 2 weeks then 1 mg/kg daily for 2 weeks; limited-antigen diet accompanies treatment. |
| Glomerulonephritis | 2 mg/kg | PO | Every 24 h | Immunosuppressive treatment for this indication is controversial. |
| Chronic hepatitis – steroid-sparing course — Initial | 2.2 mg/kg | PO | Every 24 h | Up to 14 days; Initial daily treatment for 1–2 weeks, with prednisolone/prednisone initially 1–2 mg/kg/day and response-guided steroid taper. |
| Chronic hepatitis – steroid-sparing course — Maintenance | 2.2 mg/kg | PO | Every 48 h | After 1–2 weeks; use cautiously because azathioprine itself may injure the liver. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Immune-mediated disease – exceptional use — Initial | 0.3 mg/kg | PO | Every 24 h | Exceptional cautious use only. Cats are unusually sensitive; intensive CBC monitoring and precise compounding are required. |
| Immune-mediated disease – exceptional use — Maintenance | 0.3 mg/kg | PO | Every 48 h | Reduce frequency only after careful monitoring of the initial course. |
| Refractory inflammatory bowel disease – exceptional use | 0.3 mg/kg | PO | Every 48 h | Most clinicians avoid feline azathioprine. Severe neutropenia or fatal toxicity is possible; precise compounding and close CBC monitoring are essential. |
Horses
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Immune-mediated disease | 3 mg/kg | PO | Every 24 h | Do not use in: Food-producing animals; Clinical experience is limited. |
| Autoimmune skin disease – steroid-sparing course — Initial | 1–3 mg/kg | PO | Every 24 h | Up to 30 days; First month, with corticosteroids; monitor platelets. |
| Autoimmune skin disease – steroid-sparing course — Maintenance | 1–3 mg/kg | PO | Every 48 h | After 1 month; monitor for thrombocytopenia. |
Ferret
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Inflammatory bowel disease adjunct | 0.9 mg/kg | PO | Every 24–72 h | Combined with dietary management and prednisone 1 mg/kg PO every 12–24 hours. |
Indications
- Adjunctive immunosuppression for selected canine immune-mediated hemolytic anemia cases.
- Pemphigus and selected other immune-mediated skin disorders in dogs.
- Selected canine inflammatory bowel disease or chronic inflammatory enteropathy requiring additional immunosuppression.
- Steroid-sparing combination treatment of responsive immune-mediated disease.
- Reported treatment of equine immune-mediated disease; veterinary experience is limited.
Contraindications
- Cats are particularly susceptible to marrow suppression; ordinarily avoid feline use.
- Do not use in food-producing animals.
- Known hypersensitivity. Use cautiously in hepatic dysfunction.
- Mutagenic and teratogenic potential; avoid during pregnancy when alternatives exist. Milk replacer is recommended for nursing offspring during maternal treatment.
Interactions
- Do not combine with allopurinol: inhibition of thiopurine metabolism increases toxicity.
- Other marrow-suppressive agents increase risk.
- A possible pancreatitis association with concurrent corticosteroids is unconfirmed.
- ACE inhibitors, aminosalicylates and other marrow-suppressive drugs increase hematologic-toxicity risk.
- May reduce warfarin anticoagulation or antagonize non-depolarizing neuromuscular blockers.
Adverse effects
- Myelosuppression, vomiting, diarrhea and secondary infection.
- Hepatotoxicity, often emerging in the first 2–4 weeks.
- Possible pancreatitis.
Toxicity
Overdose may cause delayed marrow suppression and gastrointestinal or hepatic injury. Consider safe early decontamination after recent ingestion and provide supportive treatment with serial CBC and biochemical monitoring.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Azathioprine 25 mg tablet | Tablet | 25 mg / tablet | PO |
| Azathioprine 50 mg tablet | Tablet | 50 mg / tablet | PO |
| Azathioprine 75 mg tablet | Tablet | 75 mg / tablet | PO |
| Azathioprine 100 mg tablet | Tablet | 100 mg / tablet | PO |
Monitoring and Administration
Check CBC during treatment, with a CBC essential at 2 weeks. Monitor liver enzymes and bilirubin closely, particularly in weeks 2–4.
Often combined with prednisone or prednisolone, although superiority over either alone is not established. Feline dosing requires careful compounding; chlorambucil is an alternative.
Keep tightly sealed at room temperature. Certain compounded oral suspensions have 60-day stability.
A 10 mg/mL injectable formulation is listed, but no specific injection route or veterinary injection dose is established for this formulation.
Check hemogram including platelets every 1–2 weeks initially and at least every 1–2 months on maintenance, with closer checks when warranted. A general recommendation reduces dose 25% at WBC 5000–7000/µL and stops below 5000/µL until recovery; the myasthenia protocol has its own thresholds. Withdraw slowly over months in recovering IMHA and monitor relapse.
Wear gloves for compounded formulations and wash hands after administration. A 50 mg/mL suspension in equal Ora-Plus and Ora-Sweet or Ora-Sweet SF has 60-day stability at 5°C or 25°C, protected from light. Reconstituted preservative-free sodium injection is used within 24 hours; no general animal injection regimen is established.