# Leucovorin (Folinic Acid): veterinary dose and monograph

> Leucovorin (Folinic Acid) is a veterinary drug. A reduced, already-active form of folate (folinic acid) that bypasses the enzyme dihydrofolate reductase (DHFR) — used to RESCUE cells from ANTIFOLATE toxicity: it is the classic antidote after high-dose METHOTREXATE (and for methotrexate… Indications include rescue after high-dose methotrexate / methotrexate overdose (antifolate antidote); prevention/treatment of folate-deficiency myelosuppression from pyrimethamine (e.g. toxoplasmosis therapy) or potentiated sulfonamides; folate repletion where a DHFR inhibitor blocks folate activation. This monograph lists 4 reference doses for dogs, cats and horses, each with route, frequency and source.

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

## At a glance

- **Drug class:** Veterinary drug
- **Also known as:** Folinic acid, Calcium folinate, Citrovorum factor, Rescuvolin
- **Species with doses:** Dogs, Cats and Horses
- **Routes:** IV, PO
- **Last reviewed:** 1 October 2026

## Indications

- Rescue after high-dose methotrexate / methotrexate overdose (antifolate antidote)
- Prevention/treatment of folate-deficiency myelosuppression from pyrimethamine (e.g. toxoplasmosis therapy) or potentiated sulfonamides
- Folate repletion where a DHFR inhibitor blocks folate activation

## Leucovorin (Folinic Acid) 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

*Leucovorin (Folinic Acid) doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Methotrexate rescue / overdose | With methotrexate: 3 mg/m² IV, IM or PO; overdose: 25–200 mg/m² q6h (15 mild – 100 mg/m² severe) until methotrexate <1×10⁻⁸ M | IV | per protocol / q6h | — |
| Pyrimethamine toxicosis / folate deficiency | 1 mg/kg | PO | q24h | — |

- Methotrexate rescue / overdose: Papich 5e: 3 mg/m² with methotrexate; intoxication 25–200 mg/m² q6h, or the same dose as the methotrexate. Plumb’s p.716 (O’Keefe & Harris): most effective within 48 h; dose by serum methotrexate level.
- Pyrimethamine toxicosis / folate deficiency: Papich 5e: 1 mg/kg q24h PO as the antidote for pyrimethamine toxicosis. Plumb’s p.716 (Greene): 5–15 mg per animal PO or parenterally once daily.

### Cats

*Leucovorin (Folinic Acid) doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Folate repletion (pyrimethamine / TMP-sulfa marrow suppression) | 1 mg/kg | PO | q24h during antifolate therapy | — |

- Folate repletion (pyrimethamine / TMP-sulfa marrow suppression): Plumb’s p.716: 1 mg/kg once daily to prevent pyrimethamine marrow toxicity (Inzana); 5 mg per cat once daily for marrow suppression (Lindsay). Papich 5e: 1 mg/kg q24h PO.

### Horses

*Leucovorin (Folinic Acid) doses for horses*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Pyrimethamine / trimethoprim-associated anaemia or neutropenia | 0.1–0.3 mg/kg | PO | q24h | — |

- Pyrimethamine / trimethoprim-associated anaemia or neutropenia: Plumb’s p.716 (Divers 2002): 0.1–0.3 mg/kg PO once daily, especially in pregnant mares; feeding green hay or pasture is a practical alternative. Papich 5e: small-animal doses may be considered for pyrimethamine toxicosis in horses.

## Contraindications

Use as a substitute for reducing/stopping the offending antifolate where indicated. Known hypersensitivity. (Timing matters in methotrexate rescue — follow the specific protocol.) In some cancer regimens leucovorin potentiates fluorouracil — relevant only in that context.

## Adverse effects

- Generally very well tolerated
- Rare hypersensitivity/allergic reaction
- In fluorouracil regimens: potentiates 5-FU toxicity (context-specific)

## Drug interactions

- Methotrexate / pyrimethamine / trimethoprim: counteracts their antifolate (marrow) toxicity (the intended rescue)
- Fluorouracil (5-FU): leucovorin ENHANCES 5-FU cytotoxicity/toxicity (relevant in specific oncology protocols)
- Phenytoin/phenobarbital: folates can lower anticonvulsant levels (theoretical)

## Pregnancy and lactation

Considered low-risk (a physiological reduced folate); use when needed.

## Monitoring

- CBC (marrow protection) during antifolate therapy
- Methotrexate levels/timing (for high-dose rescue protocols)
- Clinical response; ensure the correct agent (FOLINIC acid, not folic acid) is used

## Toxicity and overdose

Very wide safety margin — leucovorin itself is essentially non-toxic (rare hypersensitivity). The main context-specific caution is its potentiation of fluorouracil toxicity. In antifolate rescue, the "risk" is incorrect timing/dose failing to protect the host.

Management: Supportive only; no specific antidote needed (very safe). Manage any hypersensitivity reaction conventionally.

## Clinical pearls

- The antidote/"rescue" for ANTIFOLATE drugs — it bypasses the DHFR block, so it reverses methotrexate/pyrimethamine/trimethoprim marrow toxicity when ordinary folic acid cannot
- Give FOLINIC acid (leucovorin/calcium folinate), NOT plain folic acid — they are not interchangeable for rescue
- Classic uses: methotrexate rescue/overdose, and protecting the marrow during prolonged pyrimethamine/potentiated-sulfonamide (e.g. toxoplasmosis) therapy
- Very safe itself — but remember it POTENTIATES fluorouracil toxicity in those specific oncology protocols

## Mechanism of action

Folinic acid is a fully reduced folate (5-formyltetrahydrofolate) that is readily converted to the tetrahydrofolate cofactors needed for thymidylate and purine synthesis — WITHOUT requiring dihydrofolate reductase. Because antifolate drugs (methotrexate, pyrimethamine, trimethoprim) act by inhibiting DHFR, leucovorin bypasses that block and restores folate-dependent DNA synthesis in host cells ("rescue"), reversing/preventing their folate-deficiency toxicity (notably myelosuppression). (Ordinary folic acid cannot bypass the DHFR block and so does not provide effective rescue.)

## Formulations and products

- 15 mg tablet
- Injection 50 mg vial (reconstitute)
- Leucovorin / Rescuvolin — 15 mg tablet; 50 mg vial, Tablet / injection (human-label)

## Storage

Tablets: 15–30 °C, dry. Injection: reconstitute per label, protect from light, use promptly.

## 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 Leucovorin (Folinic Acid) for dogs?

Reference doses for Leucovorin (Folinic Acid) in dogs: With methotrexate: 3 mg/m² IV, IM or PO; overdose: 25–200 mg/m² q6h (15 mild – 100 mg/m² severe) until methotrexate <1×10⁻⁸ M IV per protocol / q6h (Methotrexate rescue / overdose); 1 mg/kg PO q24h (Pyrimethamine toxicosis / folate deficiency). Confirm against the label and the patient before use.

### What is the dose of Leucovorin (Folinic Acid) for cats?

Reference doses for Leucovorin (Folinic Acid) in cats: 1 mg/kg PO q24h during antifolate therapy (Folate repletion (pyrimethamine / TMP-sulfa marrow suppression)). Confirm against the label and the patient before use.

### What is the dose of Leucovorin (Folinic Acid) for horses?

Reference doses for Leucovorin (Folinic Acid) in horses: 0.1–0.3 mg/kg PO q24h (Pyrimethamine / trimethoprim-associated anaemia or neutropenia). Confirm against the label and the patient before use.

### When should Leucovorin (Folinic Acid) not be used?

Use as a substitute for reducing/stopping the offending antifolate where indicated. Known hypersensitivity. (Timing matters in methotrexate rescue — follow the specific protocol.) In some cancer regimens leucovorin potentiates fluorouracil — relevant only in that context.

### What are the side effects of Leucovorin (Folinic Acid) in animals?

Generally very well tolerated; Rare hypersensitivity/allergic reaction; In fluorouracil regimens: potentiates 5-FU toxicity (context-specific).

## 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.