From the Guidelines
The usual dose of folic acid given in combination with methotrexate is 1 mg daily or 5 mg once weekly, typically taken 24 hours after the methotrexate dose. This recommendation is based on the most recent guidelines from the American Academy of Dermatology, which suggest that folic acid supplementation can decrease the rate of adverse effects associated with methotrexate therapy 1. The guidelines also note that folic acid or folinic acid has been reported to decrease hepatic laboratory abnormalities and GI adverse effects in patients with rheumatoid arthritis.
Key Considerations
- Folic acid supplementation is essential when using methotrexate because it helps reduce the medication's adverse effects without compromising its therapeutic efficacy.
- Methotrexate works by inhibiting dihydrofolate reductase, an enzyme involved in folate metabolism, which can lead to folate deficiency and associated side effects like nausea, mouth sores, liver function abnormalities, and bone marrow suppression.
- By providing supplemental folic acid, these side effects can be minimized while maintaining the therapeutic benefits of methotrexate.
- Patients should be advised to take folic acid consistently as prescribed and not to skip doses, as consistent supplementation is key to preventing methotrexate toxicity.
Administration and Monitoring
- Folic acid is typically given daily, except for the days in which methotrexate is given, to avoid influencing efficacy 1.
- Liver function test monitoring is recommended every 3 to 6 months, assuming there are no laboratory abnormalities in the results 1.
- For patients with risk factors for hepatotoxicity, it may be reasonable to consider an alternative therapy to methotrexate, and if methotrexate is chosen, recommended hepatotoxicity monitoring is similar to that in low-risk individuals 1.
From the Research
Folic Acid Dosing with Methotrexate
- The typical dose of folic acid given in combination with methotrexate is around 5 mg/week, as recommended for rheumatoid arthritis patients to decrease the risk of methotrexate adverse effects 2.
- A study suggests that folic acid dose was dependent on the hospitals, while efficacies and hepatotoxicity of methotrexate was not basically different between patients taking less and more than 5 mg/week of folic acid 2.
- Another study proposes a pragmatic dosing schedule of 5 mg of oral folic acid given on the morning following the day of methotrexate administration 3.
- Daily folic acid supplementation is also used, with one study finding that daily use of folic acid does not appear to affect methotrexate efficacy 4.
- Weekly folic acid supplementation has been found to be a convenient and well-tolerated alternative to daily dosing in pediatric patients with inflammatory bowel disease on methotrexate, with a dose of 800 mcg/week being sufficient to maintain normal folate levels 5.
- A randomized, double-blind, placebo-controlled study found that folic acid supplementation at a dose of 1 mg/day reduced the incidence of elevated liver enzyme levels during methotrexate therapy, and as a consequence, methotrexate was discontinued less frequently in these patients 6.
Key Findings
- Folic acid supplementation does not appear to significantly reduce the effectiveness of methotrexate in the treatment of rheumatoid arthritis 3, 6.
- Folic acid supplementation can reduce the incidence of liver function test abnormalities and gastrointestinal intolerance in patients taking methotrexate 3, 6.
- The optimal dosing schedule for folic acid supplementation in patients taking methotrexate is not established, but weekly or daily supplementation at a dose of 5 mg or 1 mg, respectively, may be effective 2, 4, 3, 5, 6.