Methotrexate

Reduced by 50% In CKD 3 (eGFR 30-59), contraindicated in CKD 4/5 (eGFR <29)

• 7.5 mg – 30 mg once weekly
• Starting dose will usually be 15mg weekly, and usually increase in monthly increments of 5-10mg until disease stabilized
• Usual effective dose 10-25mg weekly
• If maximum oral dose ineffective or not tolerated, an equivalent subcutaneous route can be used instead
• Folic Acid 5 mg should be prescribed once weekly, taken the day after the methotrexate dose. This reduces adverse effects and can be increased to every day except the day of Methotrexate if adverse effects
• Pneumococcal and annual flu vaccine is recommended
• Passive immunization using VZIG recommended if exposed to chickenpox. Withhold Methotrexate for 2 weeks after Vaccination

• Pre-treatment – Hepatitis , HIV and VZV serology, FBC, U+E, CRP, LFT inc Albumin, FIB-4 score then Fibroscan if 1.3-3.25, CXR (only if risk factors for TB or other reason determined by Rheumatologist), PFTs in selected patients.

then

• FBC, U+E, CRP, LFT inc albumin at 2 weeks then monthly until stable for 3 months then 3 monthly (monthly if combined with Leflunomide). May be 6 monthly long term if low risk (at discretion of Rheumatologist).

Entering the results into a monitoring booklet will ensure that trends are not missed. Patients who do not attend for monitoring should be warned of the risk that serious adverse effects may go unnoticed. In the event of persistent failure to attend for monitoring please inform the Rheumatology department.

• WBC <3.5) withhold and discuss with rheumatology 
• Neutrophils < 1.6)
• Platelets     < 140)
• AST or ALT >100
• Albumin <30mg/l - if unexplained
• Creatinine increase >30% in 12 months
• Eosinophils >0.5 if unexplained 
• MCV > 105 – withhold and check B12, folate and TFT - treat and discuss if necessary          
• Rash or oral ulceration                        “       
• New or increasing dyspnoea or cough –withhold and treat if infection or discuss urgently if not thought infective (possible Methotrexate Pneumonitis)
• Abnormal bruising or sore throat - withhold until FBC available

• Treatment is continued indefinitely providing it remains effective and there are no significant side effects
• Methotrexate takes about 2-3 months to become effective
• During this period there are likely to be continued symptoms or signs of disease activity
• It is reasonable to use IM Depo steroid (Kenalog 40mg or Depo Medrone 80mg) up to monthly, depending on the requirements of the individual patient
• The dose required is small (eg monthly Kenalog 40mg = 1.6mg Prednisolone daily)
• If IM steroids are still required three months after starting treatment the methotrexate should be increased by 5mg

• Disease modifying drugs will not prevent all flares.
• These can be managed with IM Depo steroid as outlined above.
• If flares become more frequent, or the disease fails to settle between flares, the dosage should be increased, or an alternative discussed with the rheumatologist.

• alcoholism
• severe renal
• hepatic or haematological impairment
• immunodeficiency
• bone marrow failure with unexplained anaemia
• cytopenia 
• pregnancy
• breast feeding
• live vaccines
• co-prescription of folate antagonists eg co-trimoxazole

Caution in:

• renal impairment
• peptic ulcer
• ulcerative colitis
• ulcerative stomatitis
• diarrhoea
• debility
• localized or systemic infection inc Hepatitis B, C or TB
• Avoid conception for 3-6months after treatment stops
• Patients should be cautioned to contact GP immediately if they develop a cough or dyspnoea
• Treatment should be interrupted if there is marked GI upset usually severe stomatitis
• Caution to remain “well within” national recommendations for alcohol intake
• Serum pro-collagen III test not useful in inflammatory arthritis so not recommended
• Caution, and often not recommended in established ILD
• Withdraw during illness/dehydration – folinic acid rescue may be required if severe

Methotrexate excretion may be affected but actual toxicity is exceedingly rare when co-prescribed with:

• salicylates
• sulphonamides
• diuretics
• hypoglycaemics
• diphenylhydantoins
• tetracyclines,
• chloramphenicol
• P-aminobenzoic acid
• NSAIDs

Common effects are in bold type.

Mucocutaneous

• urticaria
• erythematous
• itch
• alopecia
• severe or increasing oral ulceration

Haematological

• neutropenia
• thrombocytopenia
• rarely, aplastic anaemia

Gastrointestinal

• GI upset
• enteritis

Other

• acute tubular necrosis
• interstitial pneumonitis
• liver fibrosis
• depression
• irritability

Secretaries 01387 241776

Helpline 01387 241095 (answering machine) Rheumatology Nurse Specialists

Department of Rheumatology doctors via Switchboard 01387 246246/RMS Advice Request