How does a healthcare provider prescribe methotrexate (methotrexate sodium) to a patient with a condition such as rheumatoid arthritis, psoriasis, or cancer, considering their medical history, age, kidney function, and other medications?

How Healthcare Providers Prescribe Methotrexate Sodium

Initial Dosing Strategy

For rheumatoid arthritis and psoriasis, start methotrexate at 7.5-15 mg orally once weekly, with rapid escalation by 5 mg every 2-4 weeks until achieving adequate disease control or reaching 20-25 mg weekly for optimal efficacy. 1

• The oral route is preferred initially due to ease of administration and similar bioavailability at typical starting doses 1
• For psoriasis specifically, dosing ranges from 7.5 mg to 25 mg weekly, administered as a single dose or divided into 3 doses over 24 hours 1
• The first dose should never exceed 0.2 mg/kg body weight, with doses increased gradually after initial laboratory results are normal 2
• Wait at least 4 weeks after each dose increase before assessing response, as clinical improvement takes this long to manifest 1

Critical Pre-Treatment Assessment

Before prescribing methotrexate, obtain the following baseline tests 2, 3:

• Complete blood count with differential and platelet counts to exclude anemia, leukopenia, or thrombocytopenia 2
• Liver function tests (AST, ALT, albumin, bilirubin) to identify pre-existing hepatic disease 2
• Renal function tests (serum creatinine, BUN, calculated GFR) to assess kidney function 2, 3
• Chest X-ray if the patient is over 40 years old and a smoker, or has underlying pulmonary disease 2
• Pregnancy test in women of childbearing potential 2
• Consider PPD testing for tuberculosis screening 2

Absolute Contraindications

Do not prescribe methotrexate if the patient has 2, 3, 4:

• Pregnancy (Category X) - causes birth defects and fetal death 2, 4
• Breastfeeding - methotrexate passes into breast milk 2, 4
• Cirrhosis or significant hepatic damage 2
• Severe anemia, leukopenia, or thrombocytopenia 2
• Creatinine clearance < 20 mL/min - methotrexate should be avoided entirely 2, 1
• History of severe allergic reaction to methotrexate 4

Dose Adjustments for Renal Impairment

Reduce methotrexate dose by 50% in patients with creatinine clearance between 20-50 mL/min, and avoid entirely if creatinine clearance is below 20 mL/min. 2, 1, 5

• Calculate actual creatinine clearance using the Cockcroft-Gault equation rather than relying on estimated GFR alone 5
• Myelosuppression is the most important cause of methotrexate-associated death and is significantly increased in renal dysfunction 2, 5
• Enhanced monitoring with CBC, liver function tests, and renal function every 2-4 weeks initially after dose adjustment is essential 5

Mandatory Concurrent Folic Acid Supplementation

All patients on methotrexate must receive folic acid supplementation: either 5 mg weekly (on a different day than methotrexate) or 1 mg daily except on methotrexate day. 1, 6

• Folic acid reduces nausea, myelosuppression, gastric toxicity, and hepatotoxicity without compromising efficacy 1, 6
• For patients on methotrexate 12.5 mg or higher, prescribe at least 5 mg folic acid weekly 1
• Exception: Do not prescribe folic acid to cancer patients unless specifically instructed, as it may reduce methotrexate efficacy 4

Ongoing Monitoring Schedule

Monitor CBC and platelet counts every 2-4 weeks for the first few months, then every 1-3 months depending on stability. 2, 1

• Liver function tests should be checked monthly 2
• Renal function (BUN, creatinine) should be monitored every 2-3 months 2
• Watch for downward trends in blood counts even if absolute values remain within normal range 1, 5
• More frequent monitoring is required during dose escalation, in elderly patients, or when taking interacting medications 3

Critical Drug Interactions to Avoid

Do not prescribe or carefully monitor when combining methotrexate with the following medications: 2, 5, 3

• NSAIDs (naproxen, diclofenac, ibuprofen, indomethacin) - reduce renal elimination of methotrexate, leading to toxicity 2, 3
• Trimethoprim-sulfamethoxazole - causes severe bone marrow suppression 2, 5
• Proton pump inhibitors (omeprazole, esomeprazole, pantoprazole) - decrease methotrexate clearance and can cause pancytopenia even at low doses 5, 7
• Penicillins - compete for renal tubular secretion 5
• Salicylates, phenylbutazone, phenytoin, sulfonamides - displace methotrexate from serum albumin, increasing toxicity 3

Route of Administration Decision Point

Switch to subcutaneous administration at the same dose if the patient shows inadequate response at 15-20 mg oral weekly or develops gastrointestinal intolerance, before further dose escalation. 1

Patient Education Requirements

Emphasize to patients that methotrexate is taken once weekly, NOT daily - mistaken daily use has led to fatal toxicity. 2, 3, 4

• Prescriptions should not be written on a PRN basis 3
• Instruct patients to avoid alcohol-containing beverages during treatment 3, 4
• Educate about early signs of toxicity: mouth sores, unusual bleeding/bruising, fever, persistent cough, shortness of breath 3, 4
• Both men and women must use contraception during treatment and for at least 3 months after stopping methotrexate 2
• Women must avoid pregnancy for at least one menstrual cycle after stopping 2

Special Considerations for Elderly Patients

Use relatively low doses in elderly patients due to diminished hepatic and renal function and decreased folate stores. 3

• Patients over 70 years should not exceed 0.2 mg/kg body weight 2
• Monitor more closely for early signs of toxicity 3
• Consider more frequent laboratory monitoring 3

When to Temporarily Stop Methotrexate

Discontinue methotrexate temporarily during severe infection or when infection is not responding to standard treatment. 2

• Restart only when the infection has completely cleared 2
• Stop immediately if opportunistic infections develop 2
• Hold methotrexate if persistent liver function test abnormalities develop for 2-3 months 2

Common Prescribing Pitfalls to Avoid

• Never escalate doses more frequently than every 2 weeks - insufficient time to assess therapeutic response or identify delayed toxicities 1
• Do not exceed 20 mg weekly in patients with risk factors including advanced age, renal impairment, or significant alcohol use 1
• Do not continue escalating if adequate disease control is achieved at lower doses - use the minimum effective dose to minimize cumulative toxicity 1
• Never prescribe methotrexate as a daily medication - this is the most common fatal prescribing error 2, 3, 8
• Do not ignore decimal point errors - methotrexate is dosed in milligrams, and decimal errors can be fatal 2