What is the recommended dose of folic acid for patients taking methotrexate (MTX)?

Folic Acid Supplementation with Methotrexate

The recommended dose of folic acid for patients taking methotrexate is at least 5 mg per week, with daily supplementation of 1-5 mg being the most common and effective regimen. 1

Dosing Recommendations

Standard Dosing

• Minimum recommended dose: 5 mg per week 1
• Common daily regimen: 1-5 mg daily except on the day of methotrexate administration 1
• Timing: Typically taken daily except on the day of methotrexate dosing to reduce side effects without compromising efficacy 1

Special Considerations

• Higher doses (up to 10 mg daily) may be considered for patients with homozygous MTHFR mutations 2
• Patients with elevated risk of methotrexate toxicity may benefit from the higher end of the dosing range (5 mg daily) 1

Benefits of Folic Acid Supplementation

Folic acid supplementation with methotrexate therapy provides several important benefits:

1. Reduced gastrointestinal toxicity: 26% relative risk reduction in GI side effects such as nausea, vomiting, and abdominal pain 3
2. Decreased hepatotoxicity: 76.9% relative risk reduction in abnormal liver function tests 3
3. Improved treatment adherence: 60.8% relative risk reduction in treatment discontinuation 3
4. Potential reduction in stomatitis/mouth sores: Though not statistically significant in all studies, there is a trend toward reduction 3

Folic Acid vs. Folinic Acid (Leucovorin)

• Folic acid is the preferred supplement for routine prevention of methotrexate side effects 4
• Folinic acid (leucovorin) should be reserved for:
  • Treatment of methotrexate toxicity
  • High-dose methotrexate regimens requiring "rescue" therapy
  • Cases of severe methotrexate-induced toxicity 2

Dosing Schedule Options

1. Daily administration: 1-5 mg daily (except on methotrexate day) is the most common approach 1
2. Weekly administration: Some evidence suggests that weekly folic acid (800 mcg) taken with methotrexate may be sufficient to maintain normal folate levels 5
3. Pragmatic approach: 5 mg oral folic acid given on the morning following methotrexate administration 6

Important Considerations

• Folic acid supplementation does not appear to significantly reduce the efficacy of methotrexate in treating rheumatoid arthritis or psoriasis 3, 1
• Higher doses of folic acid (30 mg/week) do not provide additional benefit over standard doses (10 mg/week) in reducing methotrexate toxicity 7
• Daily folic acid supplementation is preferred over intermittent dosing for most patients 4

Monitoring

• Regular monitoring of complete blood count, liver function, and renal function is essential regardless of folic acid supplementation 1
• Initial monitoring should occur every 2-4 weeks until stable dose is reached, then every 1-3 months 1

Folic acid supplementation is a crucial component of methotrexate therapy that significantly improves tolerability and safety without compromising efficacy. The evidence strongly supports routine prescription of folic acid for all patients receiving methotrexate.