Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Drug class: Vitamin (Water-Soluble B Vitamin)
Main indication: Folate deficiency — from small intestinal disease, antifolate drug therapy, or inadequate dietary intake
Available forms4 forms · 10 strengths documentedShow all ↓
Oral · solid
Tablet 0.4 mg OTCTablet 0.8 mg OTCTablet 1 mg OTC and RxCapsule 0.8 mg OTCCapsule 5 mg OTCCapsule 20 mg OTC
Oral · liquid
Compounded oral solution 1 mg/mLCompounded oral solution 0.05 mg/mL made from the 5 mg/mL injection
Injection
5 mg/mL 10 mL vials, Rx
Combination
Capsule — vitamin B12 0.5 mg with vitamin B9 0.2 mg veterinary, UKChewable cyanocobalamin tablet with methyltetrahydrofolate US
Overview
Folic acid (vitamin B9) is a water-soluble B vitamin essential for normal cellular metabolism, particularly nucleic acid synthesis and red blood cell production. It is commonly used in dogs and cats to treat or prevent folate deficiency associated with gastrointestinal disease or certain drug therapies.
Deficiency often occurs secondary to small intestinal disorders or malabsorption, although it may also develop with prolonged use of drugs that inhibit dihydrofolate reductase, or with inadequate dietary intake. Folic acid is given orally or parenterally, and supplementation may be required long-term; where the deficiency is caused by small intestinal disease or pancreatic insufficiency, lifelong monitoring and periodic replacement therapy may be needed.
Mechanism of Action (MOA): Folic acid is converted in the body to its active form, tetrahydrofolate, which acts as a coenzyme in the synthesis of purine and pyrimidine nucleotides required for DNA production. It is also essential for normal erythropoiesis and cellular replication.
Indications
Folic acid is used in dogs and cats for the treatment and prevention of folate deficiency, particularly in conditions affecting intestinal absorption or when folate metabolism is impaired.
- Folate deficiency: Used to treat confirmed deficiency associated with gastrointestinal disease, especially small intestinal inflammatory disorders or malabsorption syndromes.
- Exocrine pancreatic insufficiency (EPI): In exocrine pancreatic insufficiency, folic acid may be used when folate deficiency is documented. Assess serum folate together with trypsin-like immunoreactivity and cobalamin; cobalamin deficiency is more common in EPI and can cause treatment failure if it is not corrected.
- Drug-induced folate deficiency: Supplementation may be considered during prolonged treatment with dihydrofolate reductase inhibitors (e.g., trimethoprim, pyrimethamine, or ormetoprim). Folic or folinic acid may be used, with folinic acid generally preferred, although the clinical benefit is uncertain. Folate at 5 mg daily has also been recommended to help prevent pyrimethamine-associated bone-marrow suppression.
- Nutritional deficiency: May be used in cases of inadequate dietary intake or absorption of folate.
Dosage (Reference)
Dog
In dogs, folic acid dosing is not standardized and varies depending on the underlying condition. Dosing is typically given as a fixed amount per animal (not mg/kg).
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Folate deficiency (e.g., IBD, EPI) | PO | 400 µg – 1 mg per dog | q24h | Dosage recommendations vary and there is little evidence supporting any specific dose. When used for inflammatory bowel disease, many clinicians give it together with cobalamin (vitamin B12). |
| Alternative higher dosing | PO | 2 – 5 mg per dog | q24h | Used in some cases; evidence supporting optimal dose is limited. |
| Gluten enteropathy (Irish Setter) with markedly subnormal serum folate | PO | 0.5 – 2 mg per dog | q24h | For 2 to 4 weeks when serum folate is markedly subnormal (below about 4 µg/L), with a periodic folate assay every 6 to 12 months if it was initially decreased. |
| Reference-laboratory protocol — dogs under 20 kg | PO | 200 µg per dog | q24h | For 4 weeks. |
| Reference-laboratory protocol — dogs 20 kg and over | PO | 400 µg per dog | q24h | For 4 weeks, as for the lower weight band. |
Important dosing notes (dogs):
• Dose is given per animal (NOT mg/kg).
• There is limited evidence supporting a specific optimal dose.
• Often combined with cobalamin (vitamin B12) in gastrointestinal disease. Cobalamin is required for folate to be used, so an untreated cobalamin deficiency can itself produce a functional folate deficiency.
• Adjust therapy based on clinical response and laboratory monitoring: check serum folate and cobalamin before, during and after treatment, watch for the clinical signs of folate deficiency, and run a baseline and periodic complete blood count. Withhold food before sampling – in dogs, feeding changed the clinical interpretation of serum folate in about a third of cases in one study.
• Dose is given per animal (NOT mg/kg).
• There is limited evidence supporting a specific optimal dose.
• Often combined with cobalamin (vitamin B12) in gastrointestinal disease. Cobalamin is required for folate to be used, so an untreated cobalamin deficiency can itself produce a functional folate deficiency.
• Adjust therapy based on clinical response and laboratory monitoring: check serum folate and cobalamin before, during and after treatment, watch for the clinical signs of folate deficiency, and run a baseline and periodic complete blood count. Withhold food before sampling – in dogs, feeding changed the clinical interpretation of serum folate in about a third of cases in one study.
Cat
In cats, folic acid dosing is also not weight-based and is typically given as a fixed daily dose depending on the clinical indication.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Folate deficiency (e.g., IBD, EPI) | PO | 400 µg – 1 mg per cat | q24h | Dosage recommendations vary, and there is little evidence supporting any specific dose. |
| Prevention of deficiency (long-term sulfa/trimethoprim therapy) | PO | 2 mg per cat | q24h | Recommended during prolonged HIGH-DOSE sulfonamide/trimethoprim therapy – for example, treatment of Nocardia infection – to prevent folate depletion. |
Important dosing notes (cats):
• Dose is expressed per cat (NOT mg/kg).
• Often used alongside cobalamin supplementation in GI disease.
• Monitor serum folate and cobalamin before, during and after treatment, with a baseline and periodic complete blood count.
• Adjust therapy according to clinical response and the underlying condition, and address the proximal small intestinal disease suspected of causing the decreased serum folate.
• Dose is expressed per cat (NOT mg/kg).
• Often used alongside cobalamin supplementation in GI disease.
• Monitor serum folate and cobalamin before, during and after treatment, with a baseline and periodic complete blood count.
• Adjust therapy according to clinical response and the underlying condition, and address the proximal small intestinal disease suspected of causing the decreased serum folate.
Warnings & Precautions
Folic acid is generally safe in dogs and cats, but appropriate diagnosis and monitoring are important to ensure effective and appropriate supplementation.
- Hypersensitivity: Contraindicated in animals with known hypersensitivity to folic acid.
- Masking cobalamin deficiency: Human data indicate that folic acid can mask the signs associated with cobalamin deficiency, and that folic acid should not be given until pernicious anaemia has been excluded. In dogs and cats, measure folate and cobalamin before treatment, and identify and correct any cobalamin deficiency.
- Diagnostic evaluation required: Do not initiate therapeutic supplementation until serum folate and cobalamin levels have been measured, especially in patients with suspected gastrointestinal disease.
- Variable folate levels in GI disease: Dogs with enteropathies may have increased, normal or decreased folate levels, so supplementation should be guided by laboratory findings rather than assumed deficiency. A HIGH serum folate is a diagnostic finding, not a reason to supplement: many gut bacteria synthesise folate, so small intestinal dysbiosis can raise the serum folate while lowering cobalamin. That combination is suggestive of dysbiosis but not specific, not every affected patient shows it, and a high folate has not been shown to predict a positive response to antimicrobial treatment.
- Parenteral formulations: Some injectable products may contain additives such as aluminum or benzyl alcohol; use caution when selecting formulations.
- Pregnancy and lactation: Folic acid is safe to use during pregnancy and is distributed into milk but remains safe; requirements may be increased in lactating animals. Supplementation during pregnancy reduced the occurrence of cleft lip and/or palate in pug and Chihuahua puppies in one study, although the same effect was not seen in a colony of guide dogs.
- Choosing a product: No veterinary-labelled standalone folic acid product is listed; the standalone tablets, capsules and injection are human-labelled, and veterinary combination products containing folate also exist. When using a combination or multivitamin, check that it supplies enough folic acid to treat the deficiency without over-supplying the fat-soluble vitamins A, D, E and K.
- Folic acid is not folinic acid: Folic acid and folinic acid (leucovorin) are not interchangeable. Folinic acid is a reduced form of folic acid whose only veterinary use is as an antidote – it is the drug used for an overdose of a folate antagonist such as methotrexate – and it interferes with the action of trimethoprim and pyrimethamine.
Drug Interactions
Reported interactions mainly involve altered folate metabolism, absorption or drug response; some are theoretical or are based on human or general animal data, and may be of significance in veterinary patients. Monitoring may be required when used with the following medications.
- Dihydrofolate reductase inhibitors (e.g., trimethoprim, ormetoprim, pyrimethamine, methotrexate): May interfere with folic acid utilization and reduce its effectiveness.
- Chloramphenicol: May delay hematologic response to folic acid therapy.
- Phenobarbital: Folic acid may decrease serum phenobarbital concentrations; monitor therapeutic response.
- Primidone: May increase the risk of folate deficiency.
- Sulfasalazine: May increase the risk of folate deficiency, and may interfere with measurement of the serum folate concentration.
- Fluorouracil: Folic acid and folinic acid may increase the toxic effects of fluorouracil.
- Cholestyramine: Binds folic acid in the gut and reduces its absorption; patients on long-term cholestyramine may need folic acid and fat-soluble vitamin supplementation. Give oral folic acid at least 1 hour before, or 4 to 6 hours or longer after, the cholestyramine dose.
Side Effects & Overdose
Side Effects
Folic acid is generally well tolerated in dogs and cats and has a wide safety margin. Significant adverse effects are not expected at therapeutic doses; gastrointestinal and hypersensitivity reactions have rarely been reported, and those reports are human data.
- Gastrointestinal signs: The medicine may be given with or without food. If vomiting or illness occurs after an empty-stomach dose, give it with food or a small treat; if vomiting continues, contact a veterinarian.
- Hypersensitivity reactions: Rarely reported in humans after tablets or injections; the frequency in dogs and cats is not known.
- CNS effects (very high doses): Very high oral doses in humans – about 15 mg daily – have occasionally caused CNS effects, including difficulty sleeping, excitement and confusion.
Overdose
Folic acid is relatively non-toxic, and overdose is unlikely to result in significant clinical effects in dogs and cats.
- Minimal toxicity: Excess folic acid is either metabolized or excreted unchanged in the urine.
- Management: No specific treatment should be required after an inadvertent overdose.
Key Notes
Practical clinical points that help guide the effective use of folic acid in dogs and cats:
- Absorption site: Primarily absorbed in the proximal small intestine, making serum levels useful in assessing small intestinal function.
- Enterohepatic circulation: Undergoes enterohepatic recirculation and is excreted mainly in the urine, either as metabolites or unchanged when given in excess of the body’s requirements.
- Liver storage: Folic acid is converted to its active form principally in the liver and plasma, and folate is stored in the liver.
- CSF and RBC concentrations: Erythrocyte and cerebrospinal fluid concentrations can be significantly higher than those found in serum.
- Diagnostic marker: Serum folate and cobalamin patterns can suggest the distribution of small intestinal disease: folate reflects absorption in the proximal small intestine (jejunum) and cobalamin the distal small intestine (ileum), while both may fall in diffuse enteropathy. Interpret the pattern cautiously – it is suggestive rather than specific, and dysbiosis alters both. The reference interval for serum folic acid is about 3.5 to 11.0 µg/L (7.93 to 24.92 nmol/L).
- Wide distribution: Distributed extensively throughout the body to support cellular replication and metabolic activity.
- How well does it work: The benefit of supplementing a low serum folate in dogs and cats with gastrointestinal disease has not been clearly demonstrated. Supplementation is nevertheless considered because experimentally induced folate deficiency can have clinical consequences and folic acid is inexpensive and safe. Hypofolataemia is a weaker marker of chronic enteropathy than hypocobalaminaemia, and whether a low folate simply marks small intestinal damage or genuinely needs treatment remains unsettled.
- Getting the sample right: Handle the sample carefully: serum for folate or cobalamin should be protected from bright light and excessive heat, and haemolysis can cause a falsely ELEVATED serum folate. Pyrimethamine may produce inaccurate vitamin B12 and folic acid blood-assay results, so interpret measurements cautiously during treatment.
- Long-term folate and cobalamin: Prolonged folic acid supplementation can lower the serum cobalamin concentration, so cobalamin should be rechecked in patients on long-term folate therapy.
- What folate deficiency does: Folate and cobalamin deficiencies are recognized nutritional associations with megaloblastic anaemia, although the contribution of hypofolataemia to anaemia in dogs and cats remains uncertain. Folate deficiency is rare in these species and may result from inadequate dietary intake or intestinal malabsorption. Inherited cobalamin malabsorption is an additional cause of cobalamin deficiency, particularly in dogs.
- How common is it: The incidence of clinically significant folic acid deficiency is unknown. An association between low folate and raised homocysteine has been demonstrated in greyhounds.
- When to recheck: If clinical signs resolve, serum folate is not usually rechecked. If signs persist, rechecking the folate one week after supplementation is stopped may be helpful. In dogs with gluten enteropathy whose folate was initially decreased, consider a periodic assay every 6 to 12 months.
- Combined products and compounding: Combined cobalamin and folate products exist – a UK veterinary capsule containing 0.5 mg vitamin B12 with 0.2 mg vitamin B9, and a US chewable cyanocobalamin tablet that also contains methyltetrahydrofolate – but combination products are not recommended when a cobalamin deficiency itself needs treating. Compounded oral solutions of 1 mg/mL and 0.05 mg/mL are described, each stable for 30 days at room temperature when prepared as specified; the 0.05 mg/mL preparation is made from the 5 mg/mL injection.
- Storage: Store tablets in well-closed containers at 20 to 25 °C, protected from light and moisture. Store the injection protected from light at the same temperature, and do not freeze.
