Methotrexate
This shared care guideline sets out details for the care
of patients with
rheumatoid arthritis prescribed methotrexate. These
guidelines provide
additional limited information necessary to aid in the
treatment of
rheumatology patients. As with all shared care guidelines these
highlight
significant prescribing issues but should be used in conjunction
with the
summary of product characteristics (Data sheet) and do not replace
the drug
company information.
Click here to print this guideline in WORD format
INTRODUCTION / BACKGROUND INFORMATION
Methotrexate is a folic acid antagonist and is a disease
modifying drug for
rheumatoid arthritis
INDICATIONS FOR THE PURPOSE OF THIS
GUIDELINE
Treatment of adults with
inflammatory joint disease and autoimmune disease.
Methotrexate requires
careful monitoring to avoid toxicity. It is recommended
that oral
methotrexate be initiated after consultant recommendation.
The
prescription and supply of subcutaneous (sc) methotrexate may be advised
if:
(1) There has been a good response to oral methotrexate but patients
suffer
severe GI side effects
(2) Poor response to oral preparation
due to suspected reduced absorption.
Dosage
Oral - For both
oral and sc methotrexate, the usual dose range is 2.5mg – 20mg
once weekly.
Oral methotrexate should be prescribed as multiples of 2.5mg
tablets.
Subcutaneous - The consultant rheumatologist may prescribe sc
methotrexate
with the dose individualised for each patient.
To limit
the side effects of methotrexate, all patients should receive folic acid
5mg
orally daily except on the day they take methotrexate.
Contraindications
- Severe/significant renal or hepatic impairment
- Active acute infectious disease, evidence of immunodeficiency syndrome
- Serious cases of anaemia, leucopenia, thrombocytopenia
- Receiving drugs with antifolate properties e.g. co-trimoxazole, trimethoprim,
- Sulphonamides
- Breastfeeding
- Pregnancy - Methotrexate can affect fertility of men and women and is contra-indicated prior to conception and for at least six months after treatment. Treatment with methotrexate has the potential to affect the development of the unborn child and both men and women of childbearing age should use a reliable method of contraception to avoid the risk of an unplanned pregnancy during treatment. When planning a pregnancy it is important that both men and women on this drug discuss medication with the Rheumatology Team (at least six months before conception).
Precautions
- Elderly (consider reduction in dose)
- Bone Marrow Disease
- Renal impairment (reduce dose)
- Alcohol consumption - recommended maximum of 5-10 units per week.
Monitoring
Patients must report mouth ulcers, sore throat, fever, epistaxis, unexpected
bruising or bleeding, shortness of breath, and any unexplained illness/infection
and should be seen urgently for full blood count and liver function tests and CXR
if pulmonary symptoms.
Prior to starting therapy ,
Chest x-ray
Assessment of renal and liver function, fbc
Ongoing Monitoring:
It is recommended that all blood counts are monitored and recorded carefully.
* CBC, renal function and LFTs fortnightly for 3 months and monthly thereafter.
If there is evidence of renal impairment check that renal function has not
deteriorated after 4 weeks.
* CBC should be measured one week after any increase in dose.
* In order to monitor disease activity a 3 monthly CRP would be helpful.
* Always look at the mean corpuscular volume (MCV). A rising value may
precede marrow dysplasia…BUT check for underlying causes before stopping
treatment (B12, TFT, folate and alcohol consumption)
Stop and refer to the rheumatology team if:
* WCC falls on 3 successive occasions and/or WCC falls below 3.5 x 109.
* Platelet count falls on 3 successive occasions
* Platelet count falls below 150 x 109
* Liver enzymes especially transaminase increased x 3 upper limit of normal
* Consecutive significant fall in albumin – seek specialist opinion
* Severe nausea or diarrhoea
* Severe mouth or genital ulceration
NB: Do not stop treatment prior to surgery
Side effects
Very common > [1 in 10] > Common > [1 in 100] > Uncommon > [1 in 1000] > Rare > [1 in 10000]
> Very rare
NB. The risk of side effects indicated are relative to all the licensed uses of
methotrexate and are expected to be less common when taken at low dose on a
weekly basis.
Very common/Common:
Mouth ulcers
Nausea and diarrhoea
Hair loss
Uncommon:
Headaches
Bone marrow suppression
Lung and liver inflammation
Renal impairment
Very rare:
* Drowsiness
* Anaphylactic reaction
* Some patients report cognitive effects and if you suspect any thing like this
contact the rheumatologist
Common/Significant Drug Interactions
* Folate antagonists should be avoided – nitrous oxide, co-trimoxazole,
trimethoprim, sulphonamides, phenytoin and some antimalarials e.g.
pyrimethamine.
* NSAIDs (including aspirin) – will increase levels of methotrexate. This is not
considered to be a problem in patients with Rheumatoid arthritis as the doses
used take this interaction into account.
* Ciclosporin
* Retinoids e.g. Acitretin and Etretinate
* Clozapine
* Drugs affecting renal tubular transport
* Caution when co-prescribing hepatic or nephrotoxic drugs
* Vaccinations - Live attenuated vaccines should be avoided. For additional
information refer to the British Society of Rheumatology guidance on
vaccinations for immunosuppressed patients
http://www.rheumatology.org.uk/guidelines/clinicalguidelines/vaccineguideline
Notes
* Passive immunisation should be carried out using Varicella Zoster
Immunoglobulin (VZIG) in non-immune patients if exposed to chickenpox or
shingles.
* Flu and Pneumococcal vaccines can be given.
* Methotrexate can cause dizziness, fatigue, blurred vision and eye-irritation,
which may affect the ability to drive or operate machinery.
References
1. Summary of Product Characteristics Maxtrex (Wyeth) / Methotrexate (Mayne Pharma)
January 2006.
2. British Society of Rheumatologists Guidelines August 2000.
3. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for
rheumatoid arthritis. Z Ortiz, D Moher, BJ Shea, ME Suarez-Almazor, P Tugwell, G Wells Year:
1999. Reported at Cochrane Library
4. NPSA Towards safer use of Methotrexate
http://www.npsa.nhs.uk/site/media/documents/716_towards_safer_use_oral
_methotrexate.pdf
H L Averns Reviewed 10/09