What is the recommended oral (PO) dose of methotrexate (MTX) when converting from intravenous (IV) administration?

Methotrexate IV to PO Conversion

When converting from intravenous (IV) to oral (PO) methotrexate, the same dose should be used initially, but an increase of 2.5-5 mg in the oral dose may be necessary due to lower oral bioavailability, particularly at doses above 15 mg/week.

Bioavailability Considerations

Oral methotrexate has reduced and variable bioavailability compared to parenteral administration, which becomes more pronounced at higher doses:

• At doses ≤15 mg/week: Bioavailability is approximately 70-80% of parenteral administration
• At doses >15 mg/week: Bioavailability decreases significantly due to absorption saturation 1, 2

Conversion Guidelines

Direct Conversion Method

• For doses ≤15 mg/week: Use the same numerical dose when converting from IV to PO
• For doses >15 mg/week: Consider increasing oral dose by 2.5-5 mg to compensate for reduced bioavailability 3

Precise Conversion (when available)

• 0.1 mL of the 25 mg/mL injection solution is equivalent to a 2.5 mg oral tablet, making conversion between formulations straightforward 3

Clinical Considerations

Monitoring After Conversion

• Assess clinical response 4-8 weeks after conversion 3
• If response is inadequate after oral conversion:
  1. Consider increasing oral dose (up to maximum 25-30 mg/week)
  2. If still inadequate, switch back to parenteral administration

Maximum Dosing

• Maximum recommended oral dose: 25-30 mg/week 3
• Doses above 20 mg/week are associated with increased toxicity without proportional efficacy gains 4

Administration Schedule

• Weekly single dose is standard
• Alternative: Divided dosing (three doses given 12 hours apart) may reduce gastrointestinal side effects 3

Pitfalls to Avoid

1. Inadequate dose adjustment: Failing to account for lower bioavailability when converting high doses (>15 mg/week)
2. Premature efficacy assessment: Methotrexate takes 4-8 weeks for therapeutic effect to manifest after dose changes 3
3. Omitting folic acid: Always prescribe folic acid supplementation (5 mg weekly or 1 mg daily) to reduce toxicity 3
4. Overlooking route-specific side effects: Oral administration has higher rates of gastrointestinal side effects compared to parenteral routes 2

Special Situations

If a patient shows inadequate response to oral methotrexate at the highest tolerable dose, consider switching back to parenteral administration rather than discontinuing methotrexate therapy 3, 2.

Remember that subcutaneous administration provides higher and more consistent drug exposure than oral administration at the same dose, which may be particularly important for doses above 15 mg/week 1, 2.