What are the guidelines for using Methotrexate?

Guidelines for Using Methotrexate

Methotrexate is an effective immunosuppressant for various dermatological and rheumatological conditions, with dosing typically starting at 10-15 mg weekly and increasing gradually to 20-30 mg weekly based on clinical response and tolerability. 1

Indications

• FDA-approved for treatment of adults with severe psoriasis, rheumatoid arthritis, acute lymphoblastic leukemia, mycosis fungoides, non-Hodgkin lymphoma, and pediatric patients with polyarticular juvenile idiopathic arthritis 2
• Used off-label for many other dermatological conditions 1

Dosing Guidelines

Initial Dosing

• Start with 10-15 mg once weekly orally in healthy adults 1
• Consider lower doses (2.5-5 mg weekly) for patients with renal impairment or elderly patients 1, 3
• A test dose of 2.5-5 mg is recommended before starting full treatment 1

Dose Escalation

• Increase by 5 mg every 2-4 weeks up to 20-30 mg weekly, depending on clinical response and tolerability 1
• Allow 4-8 weeks for therapeutic effect to manifest after dose alterations 1
• If inadequate response after reaching maximum oral dose of 25 mg weekly, consider switching to subcutaneous administration 1

Route of Administration

• Oral administration is preferred initially 1
• Consider subcutaneous or intramuscular administration for patients with:
  • Poor compliance
  • Inadequate efficacy with oral dosing
  • Gastrointestinal side effects 1

Monitoring Requirements

Baseline Assessment

• Complete clinical assessment for risk factors 1
• Laboratory tests: 1
  • Full blood count with differential
  • Liver function tests (ALT, AST, albumin, bilirubin)
  • Renal function (creatinine, eGFR)
  • Hepatitis B and C screening
  • Pregnancy test if applicable
• Chest X-ray (within previous year) 1
• Consider serology for HIV in selected patients 1

Ongoing Monitoring

• Blood tests: 1
  • Every 7-14 days for first month
  • Every 2-3 months once therapy is stabilized
  • Full blood count, liver function tests, renal function
• Liver toxicity monitoring: 1
  • Monitor LFTs at least every 3 months
  • For psoriasis patients, monitor serum PIIINP (procollagen III peptide)
  • Consider specialist referral if PIIINP is >8 mg/L on two occasions or >10 mg/L on one occasion
• Pulmonary assessment: 1
  • Inquire about respiratory symptoms at each visit
  • Consider chest X-ray and pulmonary function tests for patients >40 years who smoke or have underlying respiratory disease

Folic Acid Supplementation

• Folic acid supplementation is strongly recommended with methotrexate therapy 1
• Dosing options:
  • At least 5 mg folic acid weekly 1
  • 5 mg daily except on the day of methotrexate dosing 1
• Benefits:
  • Reduces mucosal and gastrointestinal side effects
  • May have protective effect against hepatotoxicity
  • Does not affect methotrexate efficacy 1

Contraindications

Absolute Contraindications

• Pregnancy and breastfeeding 1, 2
• Alcoholism or alcoholic liver disease 1
• Immunodeficiency syndromes 1
• Bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia 1
• Hypersensitivity to methotrexate 2
• Cirrhosis 1

Relative Contraindications

• Abnormal renal function (reduce dose if eGFR <60 mL/min; avoid if <30 mL/min) 1, 4
• Abnormal liver function 1
• Active or recurrent hepatitis 1
• Moderate to heavy alcohol consumption 1
• Concomitant use of hepatotoxic drugs 1
• Active infections 1
• Recent vaccination with live vaccines 1
• Obesity (BMI >30) 1
• Diabetes mellitus 1
• Unreliable patient 1

Special Considerations

Pregnancy and Fertility

• Contraindicated during pregnancy (FDA Category X) 2
• Women should use effective contraception during treatment and for 6 months after the final dose 2
• Men should use effective contraception during treatment and for 3 months after the final dose 2
• Wait 3 months after discontinuation before attempting conception for both men and women 1

Alcohol Use

• Limit alcohol intake due to increased risk of hepatotoxicity 1
• Some physicians recommend complete abstinence while others allow limited intake 1

Drug Interactions

• Medications that may increase methotrexate toxicity: 1
  • NSAIDs (especially salicylates)
  • Trimethoprim/sulfamethoxazole and other sulfonamides
  • Penicillins, minocycline, ciprofloxacin
  • Probenecid
  • Barbiturates, phenytoin
  • Colchicine
  • Furosemide and thiazide diuretics

Pediatric Use

• FDA-approved for juvenile rheumatoid arthritis 1
• Limited data on use for pediatric psoriasis, but generally well-tolerated 1
• Monitor for abnormal liver function tests, stomatitis, and GI irritation 1

Management of Toxicity

• For bone marrow suppression: consider folinic acid (leucovorin) as antidote 1
• For hepatotoxicity: withhold methotrexate if ALT/AST >3 times upper limit of normal; may reinstitute at lower dose after normalization 1
• For significant adverse events: reduce dose or temporarily discontinue 1
• For overdose or severe toxicity: administer folinic acid (leucovorin) immediately 1

Patient Education

Before prescribing methotrexate, advise patients about: 1

• Weekly dosing schedule (emphasize that it is NOT daily)
• Delayed onset of therapeutic benefit (3-12 weeks)
• Need for contraception
• Importance of regular blood monitoring
• Signs of toxicity requiring urgent medical attention:
  • Fever/flu-like symptoms
  • Mouth ulceration
  • Unusual fatigue
  • Unexplained bruising or bleeding
  • Nausea, vomiting, abdominal pain
  • Breathlessness or cough
• Need for pneumococcal and yearly influenza vaccination
• Limiting alcohol intake
• Potential drug interactions