How do I increase methotrexate (MTX) from 7.5mg to 10mg?

How to Increase Methotrexate from 7.5mg to 10mg

Simply give four 2.5mg tablets (total 10mg) once weekly, maintaining the same weekly dosing schedule the patient is already following. 1

Practical Dosing Instructions

• Give 4 tablets of 2.5mg = 10mg total once weekly 1
• Continue the same day of the week the patient has been taking methotrexate 1
• The patient should take all tablets together in a single dose 1

Timing Considerations for Dose Escalation

• Wait at least 4 weeks after the dose increase before expecting full clinical response, as it takes this long for methotrexate dose changes to manifest their therapeutic effect 1
• The British Association of Dermatologists recommends increasing doses by 5mg increments every 4-6 weeks if improvement is less than 25-50% of baseline disease activity 1
• Since your patient received 7.5mg three weeks ago, you can proceed with the increase to 10mg now, but assess response after another 4 weeks at the new dose 1

Dose Escalation Strategy

• Standard escalation involves 2.5-5mg increases every 4-6 weeks until adequate disease control is achieved or a maximum of 25mg weekly is reached 1
• The American Academy of Dermatology guidelines describe a validated escalation protocol: 7.5mg for 2 weeks, then 10mg for 2 weeks, then 15mg for 4 weeks, with further increases based on response 1
• However, the more conservative approach of waiting 4 weeks between dose changes is preferred to properly assess efficacy and minimize toxicity risk 1

Essential Folic Acid Supplementation

• Prescribe folic acid 1-5mg daily, taken every day EXCEPT the day methotrexate is given 2
• Folic acid reduces gastrointestinal side effects (nausea, stomatitis) and hepatotoxicity without compromising methotrexate efficacy 2
• The theoretical concern is that folic acid may compete for cellular uptake if given on the same day as methotrexate 2

Monitoring Requirements

• Check CBC, liver function tests (ALT/AST), and creatinine every 1-1.5 months when increasing the dose 3
• Once the dose is stable and the patient is doing well, monitoring can be extended to every 2-3 months 3
• Assess clinically for symptoms of bone marrow suppression (easy bruising, infections), hepatotoxicity (right upper quadrant pain, jaundice), and pulmonary symptoms (new cough or dyspnea) 1, 3

Common Pitfalls to Avoid

• Do not give folic acid on the same day as methotrexate, as this may theoretically reduce efficacy 2
• Do not increase the dose more frequently than every 4 weeks, as you won't have adequate time to assess response 1
• Do not skip monitoring labs when escalating doses, as toxicity risk increases with higher doses, particularly myelosuppression and hepatotoxicity 1, 3
• Ensure the patient understands this is a WEEKLY medication, not daily, as dosing errors are a major risk factor for life-threatening toxicity 1

Risk Factors Requiring Caution

• Advanced age, renal impairment, lack of folate supplementation, hypoalbuminemia, and alcohol use all increase toxicity risk 1
• If creatinine clearance is <30 mL/min, methotrexate is contraindicated; if 30-59 mL/min, use lower doses and monitor more closely 1, 4