Use of Oral Methotrexate, Shared Care Guideline for Adults

Trust Guideline 

for 

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Use of Oral Methotrexate, Shared Care Guideline for Adults 

A guideline recommended for use 

In: 

East and North Herts NHS Trust 

East and North Herts PCT 

By: 

Consultants in East and North Herts NHS Trust, GPs in PCTs and 

Pharmacists 

For: 

Adult Patients in East and North Herts NHS Trust and PCTs 

Key Words: 

Oral methotrexate, rheumatoid arthritis, psoriasis, Crohn’s disease 

Written by: 

Andrew Hood, Principal Pharmacist 

Supported by: 

TPC Sub-Committee (Methotrexate Working Group) 

Approved by: 

Therapeutics Policy Committee 

Dr D Harvey (Chair) 

November 2006 

Ratified by: Guidelines Steering Group: Dr Rajan (Chair) 

February 2007 

Guideline issued: February 2007 

To be reviewed before: February 2009 

To be reviewed by: 

Guideline supersedes: 

Location of archived copy: 

Principal Pharmacist 

Not applicable 

Archive section of Pharmacy Intranet page 

CGSG Guideline Registration No: 033 Version No: 01 

Author: Andrew Hood Date of Issue: February 2007 Page 1 of 12 

CGSG Regn. No: 033 Version: 01 Valid until: February 2009

USE OF ORAL METHOTREXATE, SHARED CARE GUIDELINE FOR ADULTS 

East & North Herts NHS Trust 

Index 

Section 

Page Number 

Part One – Shared Care Responsibilities 

1. Hospital Specialist Responsibilities 3 

2. General Practitioner Responsibilities 4 

3. Patient’s Role 4 

4. Contact Numbers 5 

Part Two – Supporting Information 

1. Background 6 

2. Indication 7 

3. Dosage and Administration 7 

4. Prescribing Principles 8 

5. Contra-indications 8 

6. Monitoring 8 

Monitoring rheumatoid arthritis and related 

inflammatory conditions 

9 

Monitoring psoriasis 9 

Monitoring Crohn’s disease 9 

7. What To Do If Side Effects Occur 10 

8. Main Side Effects 10 

9. Drug Interactions 11 

10. Cost 12 

11. References 12 





FOR REFERENCE: 

ORAL METHOTREXATE, SHARED CARE GUIDELINE FOR ADULTS 

PART ONE – SHARED CARE RESPONSIBILITIES of SPECIALIST, GP and PATIENT 

for USE of ORAL METHOTREXATE 

1. Hospital Specialist Responsibilities (4,5,13) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Confirm diagnosis and indication for drug treatment 

Discuss the potential benefits and side effects of treatment with the patient. Ensure that the 

patient understands dosing is at weekly intervals 

Provide patient with a patient information leaflet prior to treatment 

ONLY 2.5mg tablets will be prescribed and the frequency of administration i.e. weekly will be 

clearly stated on the prescription. Use of phrases such as 'as directed' must be avoided 

Carry out baseline monitoring requirements and initiate and stabilise methotrexate therapy 

Ask the GP whether he or she is willing to participate in shared care, and agree with the GP as 

to who will discuss the shared care arrangement with the patient 

To issue NPSA blood monitoring booklets for patients commencing oral methotrexate 

Provide GP with results of baseline tests 

Clarify with the GP who is to take responsibility for monitoring and recommend frequency of 

monitoring if GP is to carry this out. Whoever takes responsibility for monitoring must act 

upon the results. 

Recommend dose and timing of any concomitant folic acid 

Monitor patient's response to therapy and communicate promptly to the GP when treatment is 

changed 

Monitor the patient for any side- effects to the methotrexate therapy and inform the GP if any 

occur 

Advise the GP on when to adjust the dose, stop treatment or consult with specialist 

Be available to give advice to GP and ensure that clear backup arrangements exist for GPs to 

obtain advice and support 

Decide when to stop therapy 

Report adverse events to the CSM and GP 





2. General Practitioner Responsibilities (4,5,13) 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Reply to the request for shared care as soon as possible 

Prescribe methotrexate as recommended by hospital specialist 

Only 2.5mg tablets will be prescribed and the frequency of administration i.e. weekly will be 

clearly stated on the prescription. Use of phrases such as 'as directed' must be avoided. 

Receive copies of any blood test results carried out in secondary care for information 

Clarify with the hospital specialist who is to take responsibility for blood tests and monitoring. 

Whoever takes responsibility for monitoring must act upon the results. 

Blood tests may be carried out by the GP by negotiation at recommended frequencies. Copies 

of blood results will be sent to the specialist. Refer to specialist if results abnormal. Where 

GPs accept responsibility for monitoring this will be recognised under NES (national enhanced 

service) 

To complete NPSA oral methotrexate monitoring booklet 

Ensure methotrexate is included on the electronic patient record in order to minimise the 

chances of prescribing other drugs that would interact with methotrexate 

Ensure that the patient understands that dosing is at weekly intervals, and which warning 

symptoms to report 

Ensure compatibility with concomitant medication 

Monitor the patient for any side-effects to methotrexate therapy and refer back to specialist 

should any serious side effect occur 

Adjust the dose as advised by the specialist 

Stop treatment on the advice of the specialist or immediately if an urgent need to stop 

treatment arises 

Report adverse events to the specialist and CSM 

3. Patient's role (13) 

 

 

 

 

 

 

 

 

Written information will be provided at the first visit 

Take the methotrexate as prescribed 

Report to the specialist or GP if he or she does not have a clear understanding of the 

treatment 

Share any concerns in relation to treatment with methotrexate. 

Inform specialist or GP of any other medication being taken, including over-the-counter 

products. 

Report any adverse effects or warning symptoms to the specialist or GP whilst taking 

methotrexate 

Inform the pharmacist that she/he is on methotrexate before purchasing any over-the-counter 

medication 

To carry NPSA oral methotrexate monitoring booklet and ensure it is updated following blood 

test 





4. Contact Numbers 

Specialist Designation Contact number 

Dr Binder Consultant Rheumatologist 01438 314333 ext 4128 

Dr Axon Consultant Rheumatologist 01707 328111 ext 4186 

Dr Ellis Consultant Rheumatologist 01438 314333 ext 4473 

Fidelma Gordon Rheumatology Nurse Specialist 01438 314333 ext 5624 

Sharon Lerpiniere Rheumatology Nurse Specialist 01438 314333 ext 5624 

Dr Ogden Associate Specialist 01438 314333 ext 4129 

Dr O'Doherty Consultant Dermatologist 01707 328111 ext 3012 

Dr Bayoumi Consultant Dermatologist 01707 328111 ext 3012 

Dr Mazzon Consultant Dermatologist 01707 328111 ext 3012 

Dr McIntyre Consultant Gastroenterologist 01707 365441 

Dr Greenfield Consultant Gastroenterologist 01707 365086 

Dr Morris Consultant Gastroenterologist 01707 365550 

Dr Sargeant Consultant Gastroenterologist 01438 314333 ext 4245 

Dr Rowlands Consultant Gastroenterologist 01707 365086 

Dr Carter Consultant Gastroenterologist 01707 365441 

Tracey Lewis 

Deborah Morris 

Inflammatory Bowel Disease 

Nurse Specialist 

Inflammatory Bowel Disease 

Nurse Specialist 

01707 365588 

01438 781680 





PART TWO – SUPPORTING INFORMATION 

1. Background (1) 

Rheumatoid Arthritis 

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease affecting 0.5 to 

1% of the population. It is believed that RA is triggered by exposure of an immunogenetically 

susceptible host to an arthritogenic antigen. A continuing auto-immune reaction ultimately leads to 

joint destruction. 

The present aim of treatment is to control joint inflammation as early as possible after diagnosis. 

This should lead to pain reduction and maintain the range of joint movement, minimise loss of 

function, prevent deformity and keep patients mobile and independent. Several factors have 

influenced the change in practice, which advocates the earlier use of disease modifying 

antirheumatic drugs (DMARDs). The rate of occurrence of bony erosions is greatest during the first 

two years of RA and there is evidence that earlier use of DMARDs slows radiological progression 

and improves function. The toxicity of DMARDs is similar to NSAIDs, particularly during the early 

stages of RA when patients’ general health is good and newer DMARDs e.g. methotrexate, are 

less toxic and more effective than those previously available. 

Methotrexate is also used for Systemic Lupus Erythematosus (SLE), ankylosing spondylitis, 

juvenile chronic arthritis, dermatomyositis and psoriatic arthritis. 

Psoriasis 

Psoriasis affects 1-2% of people in the UK. Psoriasis is a chronic cutaneous inflammatory disease 

characterised by hyperproliferation of keratinocytes and infiltration of activated T lymphocytes into 

the epidermis. The most common form of psoriasis is the chronic plaque type (psoriasis vulgaris). 

Less common forms include pustular, inverse, erythrodermic, and guttate. 

Treatment is suppressive, aimed at inducing a remission or making the amount of psoriasis 

tolerable to the patient. For the majority of patients, the disease follows a chronic course, 

interspersed with periods of remission. 

Although topical treatment is sufficient for many patients, approximately 20% need additional 

systemic drugs (including methotrexate, ciclosporin, acitretin, azathioprine, hydroxyurea 

(hydroxycarbamide), PUVA). Indications for systemic therapy include: 

 

 

 

 

 

Failure of adequate trial of topical therapy 

Repeated hospital admissions for topical therapy 

Extensive chronic plaque psoriasis in the elderly or infirm 

Generalised pustular or erythrodermis psoriasis 

Severe psoriatic arthropathy 





Crohn's disease (13,14,15) 

Methotrexate is used to treat chronically active Crohn's disease. It is usually used for patients who 

have tried other treatments unsuccessfully. It is used to reduce the amount of steroids the patient 

has to take whilst keeping symptoms under control. 

Methotrexate reduces inflammation in the bowel by dampening down the immune response. 

Methotrexate is given by intramuscular injection once a week on the same day each week for 16 

weeks. Once remission has been achieved and the patient has completed a 16-week course of 

intramuscular methotrexate they will be reviewed in the Gastroenterology clinic by the 

Gastroenterologist and Clinical Nurse specialist, to discuss treatment response, side effects and 

possible continuation of methotrexate on a reduced dose of oral methotrexate. 

Medical review will be done 6 monthly once the patient is on oral methotrexate. 

2. Indication (2) 

Methotrexate is a disease modifying agent that is being used to induce and maintain remission in 

rheumatoid arthritis. 

It is also indicated for severe uncontrolled psoriasis unresponsive to conventional therapy. 

Methotrexate is also used to treat chronically active Crohn's disease 

3. Dosage and Administration (2,3) 

NB Methotrexate is taken once a week, on the same day each week 

Rheumatoid arthritis and related inflammatory conditions 

Start at 2.5mg once a week for week 1 

5mg once a week for week 2 

7.5mg once a week from week 3 onwards 

Dosage will be reviewed at the Rheumatalogy out-patients appointment after 2-3 months 

MAINTENANCE DOSE 7.5 – 20mg once a week, according to advice 

Psoriasis 

Initial test dose of 5 – 7.5mg once a week for weeks 1 and 2 

Week 3 – blood test is done, no methotrexate is given in this week 

Week 4 – maintenance dose is decided, usually 10 – 20 mg once a week 


15mg once a week, after completing the 16 week course of intramuscular methotrexate. 

NB For all the above conditions: 

Response may take 3 – 12 weeks. Lower doses should be used in the frail, elderly or if there is 

renal impairment. 

PRESCRIPTIONS of 2.5mg TABLETS ONLY SHOULD BE ISSUED 





4. Prescribing Principles (4,5) 

All communication (ie letters, patient held monitoring and dosage records), discharge prescriptions 

and FP10s should normally carry the following details: 

 

 

 

 

Weekly dose (methotrexate always taken once a week) 

Day of the week dose taken (always same day of the week) 

Usual strength of tablets the patient takes (eg if patient takes 10mg per week on Mondays 

as four 2.5mg tablets, this should be clearly indicated on the prescription.) 

Folic acid should be prescribed as follows: 

 

 

 

Rheumatoid arthritis – 10mg once weekly, two to three days before the methotrexate is 

taken. 

Psoriasis – 5mg on five days of the week, to start on the day after the methotrexate is 

taken. 

Crohn's disease – 5mg three days per week. 

NB FOLIC ACID MUST NEVER BE TAKEN ON THE SAME DAY 

AS THE METHOTREXATE 

5. Contra-indications (3) 

Profound impairment of renal or hepatic function or haematological impairment. Liver disease, 

active infectious disease, serious cases of anaemia, unexplained leucopenia or thrombocytopenia, 

immunodeficiency syndrome(s), hepatitis C, large doses of ultraviolet light, pregnancy and breastfeeding. 

Patients with known allergy to Methotrexate. Concomitant administration of folate 

antagonists e.g. Co-trimoxazole. High alcohol intake. 

6. Monitoring (11) 

Baseline investigations – to be carried out in secondary care by specialist consultant 

Monitoring – normally to be carried out in secondary care by specialist consultant. 

GPs may undertake blood test monitoring, by negotiation, at recommended frequencies and refer 

if abnormal, and ensure that the specialist consultant receives copies of the results 

NB Blood tests should be taken on the day before methotrexate is taken – 

NEVER on the day of methotrexate. 





Monitoring details: 

Rheumatoid arthritis and related inflammatory conditions 

FBC 

LFTs 

ESR/CRP 

U&Es 

Chest X ray 

MSU 

Baseline, 

fortnightly until 4 weeks after the last dose increase 

and then 6 weekly after 2 – 3 months 

Baseline, 

fortnightly until 4 weeks after the last dose increase 

and 6 weekly after 2 – 3 months 

Every 2 – 3 months 

Baseline and then 6 – 12 monthly 

Baseline 

Baseline 

Psoriasis 

FBC 

LFTs 

U&Es 

Chest X ray 

Urinalysis 

PIIINP 

HEP C ANTIBODIES 

HELICOBACTER ANTIBODIES 

Baseline at week 3 

and then fortnightly for 2 – 3 months, 

then 3 monthly once treatment established. 

Baseline at week 3 

and then fortnightly for 2 – 3 months, 

then 3 monthly once treatment established. 

Baseline 

Baseline 

Baseline 

Checked every 3 months 

Baseline 

Baseline 


A baseline test for FBC, U&Es, LFTs, red cell folate, ESR and CRP and possibly chest X-ray are 

all done prior to commencing IM methotrexate, and then weekly for first 4 weeks and then monthly 

thereafter. 

For oral methotrexate: 

FBC 

U&Es 

LFTs 

Red cell folate 

CRP/ESR 

Baseline – then monthly 



Baseline 






7. What To Do If Side Effects Occur: 

 

Adding folic acid at the doses recommended above may help nausea, anorexia, abdominal 

discomfort and diarrhoea. Avoid on the day methotrexate is taken. 

STOP METHOTREXATE and DISCUSS with HOSPITAL SPECIALIST IF: 

WBC < 4.0 X 10 9 /L 

NEUTROPHILS twice upper limit of normal reference range 

Unexplained fall in albumin 

Rash or oral ulceration- sore mouth 

New or increasing dyspnoea or cough 

Any impairment of renal function 

Stomatitis (first indication of GI toxicity) 

Fever 

Sweating 

MCV >105fl- investigate and if B12 or folate low, start appropriate supplementation. 

Abnormal bruising or sore throat- withhold until FBC result is available. 

8. Main Side Effects (2,3,4,6,7,8) 

1. Common 

Nausea, anorexia, oral ulceration, minor hair thinning, leucopenia, abdominal discomfort, 

diarrhoea, headaches. In patients who experience gastro-intestinal side effects with 

methotrexate, folic acid may help to reduce the frequency of such side effects. The BNF 

recommendation is 5mg of folic acid weekly, however in practice the recommendation relating 

to number of days/ week folic acid treatment varies from specialist to specialist. 

2. Less Common 

Rash, bone marrow suppression, causing thrombocytopenia, neutropenia and, rarely, 

anaemia. (Therefore influenza vaccine is recommended.) 

3. Rare but Important 

• Hepatotoxicity 

Rarely methotrexate may cause liver fibrosis/cirrhosis. Where alcohol is avoided this has 

proven rare. Avoid if pre-existing liver disease. 

• Pulmonary Toxicity 

Acute pneumonitis or chronic pulmonary fibrosis may occur. This is not dose related. It 

presents with dry cough, dyspnoea and often fever. Pre-treatment chest X-ray is 

recommended 

• Methotrexate is teratogenic 

Therefore, patients of either sex should be advised to use effective contraception during 

treatment and for at least six months after stopping methotrexate. 





9. Drug interactions (2,3,4,9,10) 

Alcohol 

Anticonvulsants 

Antimalarials 

Antipsychotics 

Ciprofloxacin 

Corticosteroids 

Co-trimoxazole or 

trimethoprim 

Topical fluorouracil 

Leflunomide 

Oral neomycin 

Nitrous oxide 

Omeprazole 

Penicillins 

Probenecid 

Retinoids (acitretin) 

or ciclosporin 

Salicylates and 

NSAIDs 

Tetracycline/ 

Doxycycline 

Vaccines 

Warfarin 

Should be reduced as much as possible. One unit of alcohol per day may 

be sanctioned. 

Monitor anticonvulsant levels 

Antifolate effect of methotrexate increased by pyrimethamine (Fansidar, 

Daraprim) 

Avoid concomitant use with clozapine (increased risk of agranulocytosis) 

Monitor – as excretion of methotrexate may be reduced with use of this 

drug, giving rise to an increased risk of toxicity 

Methotrexate may have a 'steroid-sparing' effect, but there is evidence that 

the toxicity of methotrexate may also be increased and there is a risk of 

infection 

Concurrent use should be avoided 

Avoid concurrent use (toxic skin reaction) 

Greater caution required (additive liver toxicity/haematoxicity) 

Monitor – as reduced absorption of methotrexate possible 

Antifolate effect of methotrexate increased by nitrous oxide – avoid 

concomitant use 

Possible increase in methotrexate toxicity (but information from case reports 

contradictory) 

There is evidence that some penicillins can reduce the clearance of 

methotrexate, but acute methotrexate toxicity caused by this interaction has 

only been seen in a relatively small number of patients. Close monitoring is 

recommended. 

Markedly increases serum methotrexate levels. Dosage reductions are 

needed to avoid toxicity. 

Greater caution should be taken when administering retinoids (acitretin) or 

ciclosporin concurrently with methotrexate 

Use with caution and monitor methotrexate dosage. Patients should be 

advised to avoid self-medication with over the counter aspirin or ibuprofen. 

(Avoid concomitant use with azapropazone) 

Increased risk of toxicity when administered with methotrexate – careful 

monitoring required 

The concomitant use of live vaccines could cause a severe antigenic 

reaction and should be avoided. Examples of Live vaccines include MMR, 

Yellow Fever, and BCG. Flu vaccine and pneumococcal vaccines are 

inactivated vaccines and consequently may be administered to patients 

receiving methotrexate therapy. 

Warfarin - monitor INR carefully 

The British Society of Rheumatology states that NSAIDs are not contraindicated with the above 

doses of methotrexate 





10. Cost 

Dose 

Annual cost 

7.5mg/week £ 18.21 

10mg/week £ 24.29 

12.5mg/week £ 30.36 

15mg/ week £ 36.43 

Cost based on the supply of 2.5mg tablets, Drug Tariff, December 2004. 

11. References 

1) Developments in the Treatment of Rheumatoid Arthritis, NPC/UKDIPG, May 2000. 

2) BNF, No 47, March 2004. 

3) Summary of Product Characteristics for Methotrexate Sodium Tablets, Wyeth Pharmaceuticals, 

August 2003. 

4) Bedfordshire Joint Prescribing Committee Shared Care Protocol for oral methotrexate in the 

treatment of adult patients with rheumatoid arthritis or psoriasis, December 2004 

5) Addenbrooke's NHS Trust Methotrexate shared care guidelines, Sept 2003 

6) Methotrexate in Rheumatoid Arthritis, information for General Practitioners, produced by Pharmacy 

and Rheumatology Department, Bedford Hospital. 

7) Recommendation of Dr Rae, Consultant Rheumatologist, Bedford Hospital, 2000. 

8) Methotrexate and pneumonitis, Current Problems in Pharmacovigilence, Committee on Safety of 

Medicines, September 2003. 

9) Stockley, I.H, Stockley’s Drug Interactions, 6 th Edition, 2002, Pharmaceutical Press. 

10) Vaccinations in the immunocompromised person, guidelines for the patient taking 

immunosuppressants, steroids and the new biologic therapies, British Society of Rheumatology, 28 th 

January 2002. 

11) National Guidelines for the monitoring of Second Line Drugs, British Society of Rheumatology, July 

2000. 

12) ESCA: for the treatment of moderate to severe active rheumatoid arthritis- MTRAC 

13) Guidelines for monitoring and receiving methotrexate; Department of Gastroenterology, East & North 

Herts NHS Trust. 

14) Protocol for the use of maintenance methotrexate in maintaining remission in active Crohn's disease; 

Department of Gastroenterology, East & North Herts NHS Trust. 

15) East & North Hertfordshire medical gastroenterology department- patient information for 

methotrexate injection in Crohn's disease

Use of Oral Methotrexate, Shared Care Guideline for Adults

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