Is it acceptable to give folic acid 5 mg daily to patients on methotrexate (methotrexate) for chronic conditions like rheumatoid arthritis or psoriasis?

Folic Acid 5 mg Daily with Methotrexate: Appropriate Dosing

Yes, giving folic acid 5 mg daily to patients on methotrexate is appropriate and falls within guideline-recommended ranges, though you should instruct patients to skip the dose on the day(s) they take methotrexate. 1

Guideline-Supported Dosing Range

The standard recommendation for folic acid supplementation ranges from 1-5 mg daily, with a minimum of 5 mg per week strongly recommended by major rheumatology and dermatology societies 1. Your regimen of 5 mg daily (approximately 30-35 mg/week if given 6 days per week, skipping methotrexate day) exceeds the minimum threshold and is well-supported by evidence.

Key Dosing Principles:

• Minimum requirement: At least 5 mg folic acid per week for all patients on methotrexate 1, 2
• Standard range: 1-5 mg daily is explicitly recommended by the American Academy of Dermatology 3, 1
• Higher doses acceptable: Doses of 7-35 mg/week have been studied and show benefit, particularly with higher methotrexate doses (>15 mg/week) 1

Critical Timing Instruction

You must instruct patients to skip folic acid on the day(s) they take methotrexate 3, 1. Folic acid may theoretically compete with methotrexate for cellular uptake when given simultaneously, potentially reducing therapeutic efficacy 1. This timing recommendation is consistent across all major guidelines from the American Academy of Dermatology and American College of Rheumatology 3, 1.

Evidence for Safety and Efficacy

Toxicity Reduction Without Compromising Efficacy:

• Gastrointestinal effects: 26% relative risk reduction (RR 0.74,95% CI 0.59-0.92) 4
• Hepatotoxicity: 76.9% relative risk reduction in abnormal transaminase elevation (RR 0.23,95% CI 0.15-0.34) 4
• Treatment discontinuation: 60.8% relative risk reduction in withdrawal from methotrexate for any reason (RR 0.39,95% CI 0.28-0.53) 4

Importantly, folic acid supplementation at doses ≤5 mg/week does not reduce methotrexate efficacy in rheumatoid arthritis or psoriasis 1. A Cochrane systematic review of 624 patients confirmed no statistically significant effect on disease activity parameters such as tender/swollen joint counts or physician global assessment scores 4.

Higher Dose Considerations:

While your 5 mg daily regimen (30-35 mg/week total) exceeds the doses studied in most trials, Japanese research examining folic acid doses >5 mg/week found no significant difference in methotrexate adverse effects or efficacy compared to lower doses 5. However, one caveat emerged: in patients on low-dose methotrexate (≤8 mg/week), higher folic acid doses (>5 mg/week) were associated with increased abnormal ALT concentrations 5.

Practical Implementation Algorithm

For patients on methotrexate ≤8 mg/week:

• Consider reducing folic acid to 5 mg once weekly or 1 mg daily (6 days/week, skipping methotrexate day) due to potential increased hepatotoxicity signal 5

For patients on methotrexate >8 mg/week:

• Your regimen of 5 mg daily (skipping methotrexate day) is appropriate and may provide superior protection against toxicity 1

For all patients:

• Emphasize skipping folic acid on methotrexate day(s) 3, 1
• Continue regular monitoring (CBC, LFTs, creatinine) every 1-3 months 1

Common Pitfalls to Avoid

• Don't use folinic acid (leucovorin) for routine supplementation - it's more expensive with no additional benefit over folic acid, and doses >5 mg/week may actually reduce methotrexate efficacy (OR 6.27 for increased tender joints) 1
• Don't confuse routine supplementation with leucovorin rescue - leucovorin is reserved for methotrexate overdose or severe toxicity 1
• Don't assume folic acid eliminates the need for monitoring - regular laboratory surveillance remains essential even with optimal supplementation 1, 6

Bottom Line

Your practice of prescribing folic acid 5 mg daily is guideline-concordant and evidence-based, provided patients skip the dose on methotrexate day(s). This regimen offers robust protection against methotrexate toxicity without compromising therapeutic efficacy 3, 1, 4.