Rheumatology

Methotrexate is indicated for the treatment of active Rheumatoid Arthritis and some other inflammatory arthropathies. It is normally used together with Non Steroidal Anti-inflammatory Drugs particularly in the early stages of treatment. Response to treatment cannot be expected before two or three months and may not occur until after six months of treatment.

CONTRA-INDICATIONS

Pregnancy and lactation
Gross renal, pulmonary, hepatic disease
High alcohol intake
Blood dyscrasias
Teratogenesis - Stop drug 90 days before possible conception
Reduced male fertility
Care with drugs including :
- Sulphonamides
- Azathioprine
- Trimethoprim
- Co-trimoxazole
- Phenytoin
- Probenecid
- Diuretics
- NSAIDs

DOSAGE

Starting Dose 5 to 10mg oral or I.M. WEEKLY
Folic acid 5mg oral weekly taken 3 days after Methotrexate reduces adverse reactions.
If inadequate response dose can be increased to 20 mg weekly of methotrexate.
Total duration of treatment - as long as indicated by clinical condition.

MONITORING

Pre-treatment screening
monitoring weekly for first month
monitoring can then be reduced to 4-weekly

PRE TREATMENT SCREENING	EACH MONITORING VISIT
Haemoglobin Total white cell count Neutrophil count Lymphocyte count Platelet count Liver function tests Biochemical Profile Hepatitis B/C markers if abnormal LFT's	Haemoglobin Total white cell count Neutrophil count Lymphocyte count Platelet count Liver function tests

ADVERSE EVENTS

LABORATORY EVENTS	VALUES	ACTION
Leucopaenia	< 3.5 x 10 ⁹ /l	STOP + seek advice
Neutropaenia	< 2.5 x 10 ⁹ /l	STOP + seek advice
Thrombocytopaenia	< 150 x 10 ⁹ /l	STOP + seek advice
Macrocytosis	> 100	Check B12 and folate
Sequential falls in WBC or neutrophils	> 10% on 3 occasions	STOP + seek advice
Sequential falls in Platelets	> 10% on 3 occasions	STOP unless falls are from high level e.g. 600, 500, 400 x 10 ³ which are response to treatment
Elevation of liver enzymes (AST, ALT not alk phos)	>3x normal	STOP Repeat LFTs Mild transaminitis is common and normally settles.
Fall in albumin level	> 5g/l	STOP Drug Repeat LFT Early sign of liver toxicity

CLINICAL ADVERSE EVENTS	MANAGEMENT
Mouth ulcers/stomatitis	STOP drug if severe. Reduce dose if mild or moderate. Consider carbenoxalone or Difflam mouth washes. Consider other causes. Check folate levels
Cough or dyspnoea	STOP drug. CXR and pulmonary function tests. Seek advice.
Nausea and anorexia	Split dose Reduce dose Take with food, try anti-emetic. STOP if unacceptable
Increased nodule formation	Reassure patient Stop if unacceptable

Source: Dr PR Crook, Consultant Rheumatologist.