What is the proper way to take oral methotrexate (MTX) and erlotinib (erlotinib hydrochloride)?

How to Take Oral Methotrexate and Erlotinib

Methotrexate Administration

Oral methotrexate should be taken once weekly (not daily) at a dose typically ranging from 7.5 to 25 mg, with the specific day of the week clearly designated to prevent life-threatening overdose errors. 1

Dosing Schedule and Titration

• Start methotrexate at 10-15 mg once weekly, escalating by 5 mg every 2-4 weeks based on clinical response and tolerability, up to a maximum of 20-30 mg weekly 1
• The medication should be taken on the same day each week—this day must be chosen with the patient, written on the prescription, marked on the medication box, and documented in a treatment register to prevent accidental daily dosing 2
• Alternative dosing: methotrexate can be split into 3 doses given every 12 hours over 24 hours if gastrointestinal side effects are problematic 1

Route of Administration

• Oral administration is preferred initially for convenience and patient preference 1
• If oral methotrexate causes intolerable gastrointestinal symptoms, nausea, or inadequate clinical response, switch to subcutaneous administration before abandoning methotrexate entirely 1, 3
• Subcutaneous methotrexate has superior bioavailability and may reduce mucosal toxicity including oral ulcers 1, 3

Mandatory Folic Acid Supplementation

• Folic acid at least 5 mg per week must be prescribed with methotrexate to reduce gastrointestinal, hepatic, and mucosal adverse effects 1
• Folic acid should not be taken on the same day as methotrexate to avoid competitive cellular uptake 1
• If oral ulcers or other mucosal toxicity develops, increase folic acid dosing before discontinuing methotrexate 1, 3

Erlotinib Administration

Erlotinib should be taken orally at 150 mg once daily on a continuous schedule (every day without breaks) until disease progression or unacceptable toxicity occurs. 4

Timing and Food Interactions

• Erlotinib is taken once daily, continuously, as a single daily dose 4
• The FDA label specifies continuous daily dosing without scheduled breaks 4
• Erlotinib should be taken at least 1 hour before or 2 hours after food for optimal absorption (based on general tyrosine kinase inhibitor administration principles)

Combined Use of Methotrexate and Erlotinib

When these medications are used together (as in metronomic chemotherapy regimens for head and neck cancers):

• Methotrexate: 9-15 mg/m² once weekly 5, 6
• Erlotinib: 150 mg once daily, every day 5, 6
• These can be safely administered concurrently based on clinical trial data in oral cavity cancers 5, 6

Monitoring Requirements for Methotrexate

• Baseline: AST, ALT, albumin, complete blood count, creatinine, chest x-ray, hepatitis B/C serology 1
• During treatment: liver function tests and complete blood count every 1-1.5 months initially, then every 1-3 months once stable 1
• Hold methotrexate if ALT/AST rises above 3 times upper limit of normal; may restart at lower dose after normalization 1

Critical Safety Warnings

Methotrexate Overdose Prevention

• The most common and potentially fatal error is taking methotrexate daily instead of weekly 2
• Early signs of methotrexate toxicity include fever, mouth ulcers, and gastrointestinal symptoms 2, 7
• Methotrexate is absolutely contraindicated during pregnancy; women of childbearing age must use contraception and wait at least 3 months after discontinuation before attempting pregnancy 1

Drug Interactions

• Avoid concurrent use of other hepatotoxic drugs or excessive alcohol (>1 drink/day for women, >2 drinks/day for men) 1
• Renal impairment increases methotrexate toxicity risk; consider dose reduction or test dose in patients with impaired kidney function 1

Management of Intolerance

If oral ulcers or gastrointestinal symptoms develop on methotrexate:

1. First, try split dosing over 24 hours 1, 3
2. Second, increase folic acid supplementation 1, 3
3. Third, switch to subcutaneous methotrexate 1, 3
4. Only discontinue methotrexate if all above strategies fail 3