Using folic acid with methotrexate in rheumatoid arthritis
Folate (folic acid, pteroylglutamic acid) is a water soluble vitamin that is a component of enzyme systems synthesising purines and pyrimidines.
- is essential for the normal production of white and red blood cells
- folate is synthesised by bacteria of the gastrointestinal tract
- other sources include green leafy vegetables and liver
- absorption occurs in the duodenum and jejunum
- are sufficient body stores for four months supply
Rationale for using folic acid supplements
- between 7 and 30% of people discontinue methotrexate in the first year due to adverse effects (1)
- incidence of adverse events is associated with reduced adherence to methotrexate
- some of the adverse effects of methotrexate are likely to be due to folate antagonism
- common adverse effects associated with methotrexate can be divided into:
- minor effects (e.g. mouth ulcers and gastrointestinal disturbance such as nausea and vomiting)
- major effects (e.g. bone marrow toxicity and liver function test abnormalities).
Methotrexate adverse effects may be prevented with folic acid supplements
- folic acid supplementation reduces the number of people who discontinue methotrexate treatment due to side effects
Folic acid regimens
Dose
- folic acid 5mg weekly, on a different day to the methotrexate dose, is the most commonly recommended regimen from clinical studies and national guidance
- this dose should be high enough to prevent folate deficiency
- dose can be increased to 10mg if the person experiences any adverse effects to the methotrexate
Administration relative to methotrexate
- methotrexate is a folate antagonist and there has been concern that folic acid could reduce its efficacy
- has also been suggested that folic acid may interfere with the gastrointestinal absorption of methotrexate
- folic acid supplements are usually avoided on the day of oral or subcutaneous methotrexate
- taking folic acid 48 hours prior to the methotrexate dose may give added protection against gastrointestinal adverse effects (1)
Duration
- continue folic acid supplements for as long as methotrexate therapy is continued
- risk of adverse effects with methotrexate is slightly higher in the first 6 months
- risk of any adverse effects remains throughout treatment
- long-term monitoring is therefore required (1)
Reference: