Low dose methotrexate: Patient counselling

Last updated: March 09, 2020

Low dose methotrexate can cause a range of acute and chronic serious side effects such as myelosuppression, lung and liver toxicity, and mucositis. Deaths and severe harm have occurred as a result of these adverse effects: poor renal function, interacting medicines, and prescribing and/or dispensing errors have been contributing factors.

Prior to starting methotrexate patients should have been advised of the risks and benefits of the drug by their specialist team, including the need for regular blood tests, folic acid, the once weekly dose schedule, and the usual tablet strength (2.5mg). These messages should be reinforced for the duration of methotrexate therapy. Folic acid decreases the mucosal and gastrointestinal adverse effects of methotrexate and may protect against hepatotoxicity. Evidence to support the optimal regime is lacking and prescribing practice varies across the UK.

Effective patient counselling can help to mitigate some of the risks posed by methotrexate therapy, and in the green box below we outline some additional points to consider when talking to patients and their carers.

✦  Patients should also be made aware of the potential for drug interactions.They should flag up that they take methotrexate if there are any changes to the other medicines they are prescribed or if they buy products over-the-counter.

✦ Fatalities due to methotrexate are most likely secondary to myelosuppression. Patients should be counselled to promptly report symptoms such as mouth ulceration, unexplained bruising or bleeding.

✦ Intercurrent infection that fails to settle after several days or respond to conventional treatment may require, usually temporary, suspension of methotrexate.

✦  In addition patients should be aware that any illness that causes dehydration may be a reason to omit methotrexate.

✦  Use of methotrexate can rarely cause interstitial lung disease but fatalities have been reported. Symptoms are non-specific and include dry cough and dyspnoea and patients typically present within one year of starting methotrexate. Patients should seek urgent attention if they develop breathlessness or cough

✦  Methotrexate is also associated with a range of adverse liver effects including hepatitis. In patients with psoriasis taking the drug long-term, hepatic fibrosis may also occur. Patients with pre-existing liver disease, or who are at risk of developing liver disease may be more likely to develop fibrosis. Patients should be counselled to seek advice if they develop nausea, vomiting, abdominal pain or dark urine.

Nausea is one of the most common side effects with methotrexate. Some patients experience fairly mild nausea but in others it may be severe enough to affect compliance. It is dose-dependent and usually occurs within 12-24 hours of ingestion. Taking the medicine at bedtime or with food may help to reduce the severity. Antiemetics and/or giving methotrexate parenterally may also be helpful.

Patient support resources

Methotrexate treatment booklets should be issued, where appropriate, prior to starting treatment. These booklets include advice for adults taking oral methotrexate for inflammatory conditions, and a section for recording results of blood tests and dosage information.


The NHS website has a clear and thorough overview of the use of low dose methotrexate for a range of indications. It covers administration of the drug, side effects, interactions and how to manage missed doses. But there are also online resources aimed at specific groups of patients:

✦  For patients taking methotrexate for skin conditions the British Association of Dermatologists and the Psoriasis Association have both produced information leaflets. There is also a version specifically for parents and carers of children with psoriasis or scleroderma on the Medicines for Children website.

✦  The National Rheumatoid Arthritis Society website has some excellent information for patients taking methotrexate including videos about how to take the drug, interactions with other medicines and drinking alcohol, and an information leaflet.

✦  For patients taking methotrexate for inflammatory bowel disease, Crohn’s and Colitis UK have a general information leaflet and one specifically for young people.


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