What are the effects of missing a dose of methotrexate?

Effects of Missing a Dose of Methotrexate

Missing a single dose of methotrexate typically does not cause a loss of therapeutic effect if the patient has been on stable therapy for at least 10 weeks, but missing 3 or more consecutive doses can result in loss of therapeutic benefit. 1

Understanding Methotrexate Dosing

Methotrexate is typically administered as a once-weekly dose for conditions like psoriasis, rheumatoid arthritis, and other inflammatory conditions. The weekly dosage usually ranges from 7.5 to 25 mg 2. This unique weekly dosing schedule is critical to understand as daily administration can lead to potentially life-threatening toxicity 3.

Effects of Missing Doses

The consequences of missing methotrexate doses depend on several factors:

Single Missed Dose

• For patients who have reached steady state (approximately 22 weeks of therapy):
  • A single missed dose typically does not cause the methotrexate polyglutamate levels to fall below therapeutic threshold 1
  • The therapeutic effect is generally maintained
  • No significant increase in disease activity is expected

Multiple Missed Doses

• Missing 2 weeks of methotrexate:

  • Generally considered safe with minimal impact on disease activity 4
  • No significant difference in disease activity scores compared to continuous treatment

• Missing 3 or more consecutive doses:

  • Can cause methotrexate polyglutamate levels to fall below therapeutic threshold 1
  • May lead to loss of disease control
  • Increased risk of disease flare (20.5% flare rate with 4-week discontinuation vs. 7.4% in continuous treatment) 4

Disease-Specific Considerations

Rheumatoid Arthritis

• After 4 weeks of methotrexate discontinuation, disease activity scores (DAS28) increase significantly 4
• Disease activity typically returns to baseline after reintroduction of methotrexate 4

Psoriasis

• Methotrexate typically takes about 10 weeks to reach maximum effect 2
• Missing doses may delay achievement of disease control
• The British Association of Dermatologists recommends consistent weekly dosing for optimal management 2

Resuming Treatment After Missed Doses

When resuming methotrexate after missed doses:

• For 1-2 missed doses: Resume regular weekly schedule at the previous dose
• For 3 or more missed doses: Consider consulting with healthcare provider before resuming
• Disease activity typically returns to baseline after reintroduction of the medication 4

Preventing Missed Doses

To prevent accidental missed doses or overdose:

• Choose a consistent day each week for taking methotrexate 2
• Use a patient-held record book to track administration 2
• Consider using medication reminder systems 3
• Ensure proper labeling on medication packaging that emphasizes the weekly dosing schedule 3

Important Cautions

• Never attempt to "catch up" on missed doses by taking extra methotrexate
• Methotrexate overdose can cause severe toxicity affecting bone marrow, kidneys, liver, gastrointestinal tract, skin, and lungs 3
• Early signs of toxicity include fever and mouth ulceration 3
• Patients with risk factors (renal insufficiency, advanced age, lack of folate supplementation, drug interactions) are at higher risk of complications from dosing irregularities 5

When to Seek Medical Attention

Patients should contact their healthcare provider if they:

• Miss more than 2 consecutive doses
• Experience new symptoms after missing doses
• Are unsure about how to resume their dosing schedule
• Experience signs of toxicity (fever, mouth sores, unusual bruising or bleeding, shortness of breath)

Understanding the effects of missed methotrexate doses is essential for safe medication management, as both missing doses and incorrect dosing can impact treatment efficacy and patient safety.