What is the proper dosing and administration of methotrexate (MTX) and folic acid for treating sarcoidosis?

Methotrexate and Folic Acid Administration for Sarcoidosis

For sarcoidosis treatment, oral methotrexate should be initiated at 15 mg weekly with folic acid supplementation of at least 5 mg weekly (taken on non-methotrexate days) to reduce toxicity while maintaining efficacy. 1, 2

Methotrexate Dosing and Administration

Initial Dosing

• Start with oral methotrexate at 15 mg weekly 2
• Titrate to this dose within 4-6 weeks 2
• Dose range used in sarcoidosis: 7.5-15 mg weekly (can be increased up to 20-30 mg if needed) 3, 4, 5

Route of Administration

• Begin with oral administration 2
• If inadequate response or intolerance to oral methotrexate:
  • Consider split dosing (dividing the dose over 24 hours) 2
  • Switch to subcutaneous administration (higher bioavailability, fewer GI side effects) 2

Duration of Treatment

• Continue for at least 6 months to evaluate efficacy 5
• Successful treatment may require longer duration (16-36 months reported for complete remission in cutaneous sarcoidosis) 5
• Long-term treatment (up to 30 months) may be necessary for maintenance 3

Folic Acid Supplementation

Dosing

• Minimum 5 mg of folic acid weekly 1
• Increase to 5 mg daily for patients experiencing side effects or on higher methotrexate doses 1

Timing

• Administer folic acid daily EXCEPT on the day methotrexate is taken 1
• This timing prevents interference with methotrexate efficacy while reducing toxicity 1

Monitoring

Initial Monitoring

• Complete blood count (CBC)
• Liver function tests (ALT/AST)
• Renal function tests
• Baseline chest X-ray or pulmonary function tests for pulmonary sarcoidosis 6

Ongoing Monitoring

• Monitor every 1-1.5 months when starting or increasing methotrexate dose 1
• Once stable, monitor every 1-3 months 1
• Parameters to monitor:
  • CBC
  • Liver function tests
  • Renal function
  • Clinical response (symptoms, organ function)

Common Pitfalls to Avoid

• Omitting folic acid supplementation: Leads to increased methotrexate toxicity and reduced treatment adherence 1
• Administering folic acid on the same day as methotrexate: May reduce methotrexate efficacy 1
• Insufficient methotrexate dosing: Starting with doses <15 mg weekly may lead to inadequate response 2
• Premature discontinuation: Clinical improvement may take 8-12 weeks to manifest 3
• Failure to switch to subcutaneous administration: When oral methotrexate is ineffective or poorly tolerated, switching to subcutaneous route before abandoning methotrexate altogether 2

Clinical Efficacy

• Methotrexate has demonstrated effectiveness in various forms of sarcoidosis:
  • Complete remission in 75% of cutaneous sarcoidosis cases 5
  • Improvement in pulmonary function in 63% of cases 4
  • Effective as a corticosteroid-sparing agent, allowing 35-75% reduction in steroid doses 3
  • Noninferior to prednisone as first-line treatment for pulmonary sarcoidosis 6

By following this structured approach to methotrexate and folic acid administration, clinicians can optimize the efficacy of treatment while minimizing toxicity in patients with sarcoidosis.