Shared Care
Guideline
Methotrexate tablets
For the treatment of:
Inflammatory arthritis in adults ( 16 years old)
For the latest information on interactions and adverse affects, always consult the latest version
of the Summary of Product Characteristics (SmPC), which can be found at:
www.medicines.org.uk
These guidelines are based on the monitoring criteria of the British Society of Rheumatology,
published in the following reference:
Chakravarty, K., McDonald, H., Pullar, T. et al. (2008) BSR/BHPR guideline for diseasemodifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of
Dermatologists. Rheumatology 47(6), 924-925.
Authors: Dr Kelsey M Jordan (Consultant Rheumatologist, BSUH NHS Trust)
Dr Stewart E Glaspole (Pharmacist, BSUH NHS Trust/ BHCPCT)
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 1 of 9
Drug Name
Methotrexate 2.5mg tablets.
Indications for use within the protocol
Inflammatory arthritis diagnosed by a Rheumatologist with active joint inflammation
usually supported by indices of inflammation.
Duration – most drugs require up to 3 to 4 months trial to assess efficacy (including
the time required for dose stabilisation). Therapy is continued providing the drug is
working and that any side effects are tolerated by the patient. Relapse is common
after withdrawal of therapy.
Background
Methotrexate is used as a disease modifying agent to induce and maintain remission
in several types of rheumatic disease. It can reduce inflammation and affect the
immune system and is therefore used for a number of other conditions.
Pharmacology
Methotrexate inhibits the enzyme dihydrofolic acid reductase, thus interfering with
DNA synthesis, repair, and cellular replication. The precise mechanism of action in
rheumatoid arthritis is unknown. It may affect immune function and clarification of its
effect on immune activity and the relation of this to rheumatoid immunopathogenesis
await further studies.
Dosage and administration
Methotrexate is usually taken in tablet form once a week on the same day of each
week. It should be swallowed whole, not crushed or chewed and taken with food.
Methotrexate tablets are available as 2.5mg or 10mg tablets; however it is standard
practice to only use the 2.5mg strength to avoid the risk of confusion and potential
overdose. Initially 7.5mg to 15mg is given once a week (1st prescription from
secondary care). The weekly dose may be adjusted by the consultant in increments
of 2.5-5mg, according to clinical response at intervals of 2-4 weeks. The maximum
dose is 25mg once a week. A clinical response usually occurs at 3-12 weeks. Lower
doses are used in patients with impaired renal function.
Folic acid 5mg once weekly should be given on a different day to the methotrexate
dose (usually 2 days post or prior).
Contraindications to use
Methotrexate is contra-indicated in

significant renal impairment

the presence of severe/ or significant hepatic impairment including liver diseases
such as fibrosis, cirrhosis, and recent or active hepatitis

active infectious disease

overt or laboratory evidence of immunodeficiency syndrome(s)

Serious cases of anaemia, leucopenia or thrombocytopenia

Patients with a known allergic hypersensitivity to methotrexate.
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 2 of 9
Monitoring
The British Society for Rheumatology (BSR) recommends precise monitoring to be
carried out for this drug. The requirements are summarised in the following table.
a. Pre-treatment
assessment
FBC, U&E, LFT’s, CXR
b. Ongoing Monitoring

FBC fortnightly until 6 weeks after last dose increase

Provided it is stable, FBC monthly thereafter (may be
reduced to every two months on advice from
secondary care)

LFT's (incl. AST or ALT) with each blood test

U&E's 6-12 monthly (more frequently if there is any
reason to suspect deteriorating renal function)
Additional monitoring
not required but useful
ESR and/or CRP every three months
WBC
<4 x 109/l
Withhold until discussed with the
Specialist or his/her team
Neutrophils
< 2 x 109/l
Withhold until discussed with the
specialist or his/her team
Platelets
< 150 x 109/l
Withhold until discussed with the
specialist or his/her team
>2-fold rise in AST, ALT
Withhold until discussed with the
specialist or his/her team
(from upper limit of reference range)
Unexplained fall in albumin
Withhold until discussed with the
specialist or his/her team
Rash or oral ulceration
Withhold until discussed with the
specialist or his/her team
New or increasing dyspnoea or cough
Withhold until discussed with the
specialist or his/her team
MCV>105fl
Investigate and if B12 or folate low start
appropriate supplementation
Significant deterioration in renal function
Reduce dose (discuss with the specialist
or his/her team)
Abnormal bruising or sore throat
Withhold until FBC result available
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 3 of 9
Undesirable effects
The main adverse effects include:

Common – nausea, anorexia, oral ulceration, minor hair thinning, abdominal
discomfort, diarrhoea, headaches

Uncommon – rash, bone marrow suppression, causing thrombocytopenia,
neutropenia, and rarely anaemia. Patients should be warned to report a sore
throat and abnormal bleeding/bruising

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.
Additional cautions
When the patient has had close contact with chicken pox or shingles seek secondary
care advice using the contact details below
Contacting secondary care
If the patient’s Consultant is not available, one of the other Consultants or Specialist
Registrars will be able to help. Please call the Rheumatology department at RSCH
on 01273 696955 x4631/3553 or PRH on 01444 441881 x 5432/5984
Out of hours
Urgent problems should be referred to the medical team on call, contacted via RSCH
switchboard on 01273 696955 or the PRH switchboard on 01444 441881
Pregnancy and Lactation

Methotrexate is teratogenic and there is a theoretical risk of sperm mutation in
males, therefore methotrexate should not be used during pregnancy.

Patients of either gender should use adequate contraception during treatment
and wait for at least 3 months after discontinuation of methotrexate before trying
to conceive.

Methotrexate is excreted into breast milk in low concentrations (less than 10% of
those in plasma.)1 It is not known whether these small amounts are potentially
harmful to the developing child. In the absence of a clear evidence base, and
because there is a danger of accumulation within fetal tissues, paediatric advice
suggests avoidance of methotrexate during breast feeding2.
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 4 of 9
Interactions
DO NOT CO-PRESCRIBE folate antagonists such as trimethoprim or
co-trimoxazole (Septrin®) with methotrexate
Other drugs which should be avoided include:
Acitretin, chloramphenicol, sulphonamides, tetracyclines, thiazide diuretics,
probenicid, sulfinpyrazone, oral hypoglycaemics, nitrous oxide and any drugs with
suspected or confirmed hepatotoxic or nephrotoxic effects.
Methotrexate is immunosuppressive and may therefore reduce immunological
response to concurrent vaccination. Severe antigenic reactions may occur if a live
vaccine is given concurrently. AVOID LIVE VACCINES.
NB There are no contra-indications to using NSAIDs with doses of weekly
methotrexate  25mg.
Consultant / hospital responsibilities
It is the hospital team’s responsibility to:

Identify those patients who will benefit from treatment with methotrexate

Undertake pre-treatment monitoring of full blood count, liver function tests,
creatinine and chest x-ray and record Varicella status

Provide the first month’s prescription for methotrexate (and folic acid) and
provide written information on treatment to the patient and/or carers (including
the patient held record booklet)

Provide the patient with monitoring blood forms whilst on treatment with copies of
results sent to the GP (unless the GP chooses to take responsibility for both
prescribing and monitoring)

Undertake responsibility to act on pathology lab results (unless the GP chooses
to take responsibility)

Review efficacy of treatment at regular intervals and ensure any drug treatment
changes are communicated to the GP

Communicate any changes in frequency of pathology testing to the GP

Provide access to back up and support facilities

Report any adverse events to the CSM

Evaluate any adverse events reported by the GP.
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 5 of 9
GP responsibilities
It is the GP’s responsibility to:

Return the shared care agreement letter to the consultant to indicate agreement
with this guideline. If for any reason the GP is unhappy with the arrangements
they should contact the appropriate hospital specialist

Prescribe methotrexate at the dose recommended by the specialist. Only
prescribe 2.5mg tablets. Any decision to alter or discontinue treatment should be
taken after discussion with the hospital specialist

Prescribe folic acid as recommended by the hospital specialist (usually 5mg
weekly)

Check for possible drug interactions when newly prescribing or stopping
concurrent medication (see interaction section)

Encourage patients to carry an up to date methotrexate patient held record
booklet

Report any suspected or actual adverse drug reactions to the hospital specialist
and the CSM

Undertake an urgent full blood count to check for leucopenia in patients
developing significant infection, or multiple mouth ulcers

Offer advice to the patient in keeping their patient held record booklet up to date

Record results, when possible, in the patient held record booklet.
Patient responsibilities
It is the patient’s responsibility to:

Report side effects to any member of the health care team

Carry an up to date methotrexate patient held record booklet

Attend for blood testing when required to do so.
Information to the patient
The outpatient clinic will provide the patient with information about their treatment
and a patient held record booklet.
Information about the patient to be received by the GP from the consultant
Please refer to the shared care request letter attached. Two copies of this letter will
be sent to the GP for each patient.
Patient information to be received by the consultant from the GP
In order for GPs to agree formally to this shared care protocol, it is requested that
both the shared care request letters attached be signed and one returned to the
hospital specialist requesting shared care.
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 6 of 9
References
1. Johns DG, Rutherford LD, Keighton PC, Vogel CL. Secretion of methotrexate into
human milk. Am J Obstet Gynecol 1972; 112:978–80.
2. Committee on drugs, American Academy of Pediatrics. The transfer of drugs and
other chemicals into human milk. Pediatrics 1994; 93:137–50.
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 7 of 9
Confidential shared care request
Consultant name
Consultant address
Date
GP Name
GP Address
Methotrexate in inflammatory arthritis in adults ( 16 years old)
Patient Name: Patient Hospital number: Patient Address: Patient NHS Number: Dear Dr.
Your patient has been commenced on:
Methotrexate, at a dose of:
It would be appropriate for this patient’s therapy to be shared between primary and
secondary care. The enclosed Shared Care Guideline provides additional
information to support you in this. Please sign both copies of this letter to indicate
your agreement and return one copy to my office; the other should be placed in the
patient’s notes at your practice.
Yours sincerely,
Consultant name
GP signature
Print name
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 8 of 9
Date
Confidential shared care request
Consultant name
Consultant address
Date
GP Name
GP Address
Methotrexate in inflammatory arthritis in adults ( 16 years old)
Patient Name: Patient Hospital number: Patient Address: Patient NHS Number: Dear Dr.
Your patient has been commenced on:
Methotrexate, at a dose of:
It would be appropriate for this patient’s therapy to be shared between primary and
secondary care. The enclosed Shared Care Guideline provides additional
information to support you in this. Please sign both copies of this letter to indicate
your agreement and return one copy to my office; the other should be placed in the
patient’s notes at your practice.
Yours sincerely,
Consultant name
GP signature
Print name
MTX SCG
Document status Final/Draft: Final 13 Jan 2009
Date of next review if final: 13 Jan 2010
Page 9 of 9
Date