Methotrexate toxicity: warning signs and weekly dosing errors

Methotrexate interferes with how fast-dividing cells copy themselves. That is helpful in overactive immune conditions and some cancers, and it is also why it can affect bone marrow, the gut lining, the liver and the lungs. The NHS says serious side effects are rare, but it lists what to look for and says doctors monitor people closely so that concerns are found at routine check-ups.

This page focuses on toxicity, not on the full medicine guide. For how blood tests are used, see the related monitoring page.

For autoimmune conditions, and less commonly some cancer regimens, methotrexate is taken once a week. The MHRA reported that between January 2006 and July 2020 it knew of 11 Yellow Card reports of serious toxicity from inadvertent daily dosing of once-weekly methotrexate in the UK, 4 of them since January 2016. Overdose can cause low white cells, platelets and red cells, mouth and gut ulceration and bleeding; some reports were fatal, with events such as sepsis, kidney failure and aplastic anaemia.

The MHRA advice therefore asks prescribers to check the patient can understand and comply with weekly dosing, agree the day of the week with the patient, write it in full on the prescription, and warn the patient and carers of the risk of fatal accidental overdose. Pharmacists write the day on the pack, demonstrate the patient card and encourage the person to write the day on it and carry it. If you think you have taken too much, seek medical advice promptly.

The NHS also says that if you take methotrexate once a week you should take it on the same day each week, and that cancer treatment may involve more than one dose a week given in hospital. Never adjust the schedule yourself.

The NHS tells people to tell their doctor or call 111 immediately for the following serious side effects, which it describes as rare.

Loss of appetite, nausea, stomach pain, diarrhoea, headaches, tiredness and hair loss are listed by the NHS as common, happening in more than 1 in 100 people. The NHS notes hair loss is unlikely to be permanent. Persistent mouth ulcers or severe sickness can be early signs of too much medicine, so they are worth reporting rather than waiting out. Skin can also become very sensitive to sunlight, producing a sunburn-like reaction, so the NHS advises staying out of bright sun, using high-factor sunscreen and avoiding sun beds.

For headaches, the NHS suggests paracetamol and advises against NSAIDs such as ibuprofen. Folic acid is often prescribed alongside methotrexate to reduce side effects, and it should not be taken on the same day as methotrexate.

The NHS says that at the start of treatment you will have a check-up and blood tests to check your blood, liver and kidneys every 1 to 2 weeks, then every 2 to 3 months once the dose is settled. Keep the booklet where results and doses are recorded, and take it to every appointment.

Some antibiotics and anti-inflammatory painkillers can raise methotrexate levels or add to its effects, so always tell prescribers and pharmacists you take it. Report suspected reactions through the Yellow Card scheme.