Can I take folic acid with methotrexate (MTX) 7.5mg and what is the recommended dose?

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Methotrexate 7.5mg and Folic Acid Supplementation

Yes, you should absolutely take folic acid with methotrexate 7.5mg, at a dose of 1-5 mg daily, taken every day EXCEPT on the day you take your methotrexate. 1, 2

Why Folic Acid is Essential

  • Folic acid supplementation is strongly recommended for all patients on methotrexate therapy to reduce toxicity without compromising treatment effectiveness 1, 2
  • Methotrexate works as a folate antagonist, which is part of its therapeutic mechanism but also causes many side effects—folic acid helps replenish depleted folate stores 2
  • Lack of folate supplementation is a major risk factor for methotrexate-induced hematologic toxicity and other serious adverse effects 1, 2

Specific Dosing Instructions

  • Take 1-5 mg of folic acid daily 1, 2
  • Skip the folic acid on the day(s) you take methotrexate to avoid potential interference with methotrexate's cellular uptake and therapeutic effect 2
  • At your dose of 7.5mg weekly methotrexate, a minimum of 5 mg folic acid per week total is recommended 2, 3
  • A practical regimen: Take 1 mg folic acid daily for 6 days per week (skipping your methotrexate day), which gives you 6 mg weekly 2

Benefits You Can Expect

  • 74% reduction in gastrointestinal side effects like nausea, vomiting, and abdominal pain 4
  • 77% reduction in abnormal liver enzyme elevations 4
  • 60% reduction in treatment discontinuation for any reason 4
  • Reduced risk of mouth sores and stomatitis 4
  • No reduction in methotrexate's effectiveness when folic acid is dosed properly 1, 2, 4

Critical Timing Rule

  • The reason to skip folic acid on methotrexate day is that folic acid may theoretically compete with methotrexate for cellular uptake when both are present simultaneously, potentially reducing methotrexate's ability to enter cells 2
  • This timing strategy maintains full therapeutic benefit while maximizing side effect protection 2

Important Distinctions

  • Use folic acid (not folinic acid/leucovorin) for routine supplementation—it's less expensive and equally effective 1, 2, 5
  • Folinic acid (leucovorin) is reserved only for methotrexate overdose or severe toxicity situations 2, 6, 5
  • Large doses of folate (>5 mg/week of folinic acid) may reduce methotrexate efficacy, but standard folic acid dosing at 1-5 mg daily does not 1, 2

Monitoring Still Required

  • Continue regular blood work monitoring (liver function tests, complete blood count, kidney function) every 3-6 months even with folic acid supplementation 1, 2
  • Folic acid reduces side effects but doesn't eliminate the need for safety monitoring 2, 3

Common Pitfall to Avoid

  • Do not take folic acid on the same day as methotrexate—this is the single most important timing instruction to preserve methotrexate's effectiveness 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Methotrexate and Folic Acid Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Methotrexate Prescribing Protocol for Rheumatoid Arthritis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Inadvertent Methotrexate Toxicity

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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