# Leflunomide: veterinary dose and monograph

> Leflunomide is a veterinary drug. An IMMUNOSUPPRESSANT (a pyrimidine-synthesis inhibitor) used as a steroid-sparing agent for canine (and some feline) IMMUNE-MEDIATED diseases — immune-mediated haemolytic anaemia (IMHA), immune-mediated polyarthritis (IMPA)… Indications include immune-mediated haemolytic anaemia / thrombocytopenia — steroid-sparing; immune-mediated polyarthritis (IMPA); reactive histiocytosis / histiocytic disorders. This monograph lists 2 reference doses for dogs and cats, each with route, frequency and source.

Source: https://vetmasterji.com/drugs/leflunomide · Last reviewed: 2026-10-01

## At a glance

- **Drug class:** Veterinary drug
- **Also known as:** Arava, Lefno, Lefumide
- **Species with doses:** Dogs and Cats
- **General dose range:** 2–4 mg/kg PO q24h — check the species tables for the indication
- **Routes:** PO
- **Last reviewed:** 1 October 2026

## Indications

- Immune-mediated haemolytic anaemia / thrombocytopenia — steroid-sparing
- Immune-mediated polyarthritis (IMPA)
- Reactive histiocytosis / histiocytic disorders
- Inflammatory bowel disease and other immune-mediated diseases (adjunct/steroid-sparing)

## Leflunomide dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

### Dogs

*Leflunomide doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Immune-mediated disease (steroid-sparing) | 2–4 mg/kg | PO | per day (once daily or 2 mg/kg q12h), then taper | — |

- Immune-mediated disease (steroid-sparing): Papich 5e: start 2 mg/kg/day; if tolerated increase to 4 mg/kg/day (2 mg/kg q12h), then taper to 2 mg/kg q24h and by 25% steps once stable. Plumb’s p.714: IMHA 4 mg/kg PO q24h (Chabanne); reactive histiocytosis 2–4 mg/kg once daily to a trough of 20 µg/mL (Foil); transplant 4–6 mg/kg q24h. Monitor CBC and liver enzymes.

### Cats

*Leflunomide doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Immune-mediated disease | 2 mg/kg | PO | q24h for 2 days, then q48h | — |

- Immune-mediated disease: Papich 5e: 2 mg/kg per day for 2 days, then 2 mg/kg q48h PO. Plumb’s p.714 (Bennett 2005): rheumatoid arthritis 10 mg per cat daily with methotrexate 2.5 mg three times on one day weekly, reducing to 10 mg twice weekly once improved. Monitor CBC.

## Contraindications

Pregnancy (teratogenic — long-lived active metabolite; important handler/breeding consideration). Pre-existing significant myelosuppression or hepatic disease. Active serious infection (immunosuppression). Known hypersensitivity. Concurrent live vaccines. Handle with care.

## Species-specific warnings

> **Caution:** Cats: Usable in cats (an advantage over azathioprine) — monitor CBC and liver values; titrate to effect/level.

## Adverse effects

- Bone-marrow suppression (anaemia, thrombocytopenia, leukopenia) — dose-related
- GI upset (vomiting, diarrhoea, anorexia)
- Hepatic enzyme elevation (less than azathioprine)
- Lethargy; increased infection risk (immunosuppression)

## Drug interactions

- Other immunosuppressants: additive immunosuppression (often intentional, with steroids)
- Hepatotoxic/myelosuppressive drugs: additive toxicity
- Live vaccines: avoid
- Cholestyramine/activated charcoal: rapidly eliminate the active metabolite (used to accelerate washout in toxicity/pregnancy)

## Pregnancy and lactation

Contraindicated in pregnancy — teratogenic, with a long-lived active metabolite (washout with cholestyramine may be needed). Avoid in breeding animals.

## Monitoring

- CBC regularly (marrow suppression) and liver enzymes
- Teriflunomide blood level where available (target ~20 µg/mL) to guide dosing
- Clinical/disease response (e.g. rising PCV/platelets in IMHA/ITP); infection surveillance
- Taper concurrent glucocorticoids as control is achieved

## Toxicity and overdose

Dose-related bone-marrow suppression (the key monitor), GI toxicity, and hepatic enzyme elevation (generally less than azathioprine). Immunosuppression brings infection risk. The long half-life of the active metabolite means toxicity (and teratogenic risk) can persist — cholestyramine can accelerate its elimination if needed.

Management: No direct antidote, but CHOLESTYRAMINE (or activated charcoal) markedly speeds elimination of the active metabolite (teriflunomide) via interrupted enterohepatic recirculation — useful in overdose/severe toxicity/urgent washout. Otherwise discontinue and provide supportive care for myelosuppression (antibiotics ± G-CSF) and GI/hepatic effects; monitor CBC.

## Clinical pearls

- A steroid-sparing immunosuppressant that blocks lymphocyte pyrimidine synthesis — useful for IMHA/IMPA/thrombocytopenia and reactive histiocytosis, and (unlike azathioprine) usable in cats
- Titrate to the teriflunomide blood level (~20 µg/mL) where available, and to the CBC — bone-marrow suppression is the main dose-limiter
- Its active metabolite is long-lived and TERATOGENIC — avoid in pregnancy/breeding, handle with gloves, and remember CHOLESTYRAMINE can force a rapid washout if needed
- Combine with glucocorticoids and taper steroids as remission is achieved

## Mechanism of action

Leflunomide is a pro-drug converted to its active metabolite teriflunomide, which inhibits dihydro-orotate dehydrogenase — the rate-limiting enzyme of de-novo PYRIMIDINE synthesis. Rapidly proliferating activated lymphocytes depend on de-novo pyrimidine production, so their proliferation and function (T- and B-cell responses, antibody production) are preferentially suppressed, producing immunosuppression. It also has some tyrosine-kinase-inhibitory/anti-inflammatory effects. The active metabolite has a long half-life (relevant to its teratogenicity and monitoring).

## Formulations and products

- 10 / 20 mg tablet
- 100 mg tablet
- Arava / Lefno — 10 / 20 / 100 mg tablet, Tablet (human-label)

## Storage

Tablets: 15–30 °C, dry, protect from light; handle with gloves (teratogenic).

## Before you use this dose

> **Caution:** Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

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## Frequently asked questions

### What is the dose of Leflunomide for dogs?

Reference doses for Leflunomide in dogs: 2–4 mg/kg PO per day (once daily or 2 mg/kg q12h), then taper (Immune-mediated disease (steroid-sparing)). Confirm against the label and the patient before use.

### What is the dose of Leflunomide for cats?

Reference doses for Leflunomide in cats: 2 mg/kg PO q24h for 2 days, then q48h (Immune-mediated disease). Confirm against the label and the patient before use.

### When should Leflunomide not be used?

Pregnancy (teratogenic — long-lived active metabolite; important handler/breeding consideration). Pre-existing significant myelosuppression or hepatic disease. Active serious infection (immunosuppression). Known hypersensitivity. Concurrent live vaccines. Handle with care.

### What are the side effects of Leflunomide in animals?

Bone-marrow suppression (anaemia, thrombocytopenia, leukopenia) — dose-related; GI upset (vomiting, diarrhoea, anorexia); Hepatic enzyme elevation (less than azathioprine); Lethargy; increased infection risk (immunosuppression).

## Sources

- Plumb's Veterinary Drug Handbook
- Merck Veterinary Manual, 11th edition
- Papich, Papich Handbook of Veterinary Drugs, 5th edition

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VetMasterJi is a clinical decision-support and education platform for veterinary professionals and students. It does not provide veterinary advice, diagnosis or treatment for specific animals. All drug doses, calculators and differentials are references that must be independently verified before clinical use; the attending registered veterinarian remains solely responsible for every clinical decision.