Managing interactions with methotrexate

Published

Guidance on frequently asked questions on medicine interactions with low dose methotrexate.

Using low dose methotrexate

Methotrexate is an immunosuppressant given once weekly. Low doses of methotrexate (less than 25mg/week) are given for conditions including rheumatoid arthritis and psoriasis. Higher doses of methotrexate are used for cancer. Its use may be associated with several serious side effects, including blood disorders, liver cirrhosis and pulmonary toxicity.

Methotrexate is only prescribed by specialists, for example, rheumatologists. It involves regular monitoring.

Advice is provided for common interactions with low dose methotrexate.

Pharmacokinetics of methotrexate

When given in low doses, methotrexate is rapidly absorbed from the gastrointestinal tract.

It is cleared from the body mainly by the kidneys via glomerular filtration and active transport.

Any medicine that can adversely affect the renal function could cause the concentration of methotrexate in serum and in tissues to increase rapidly. This can lead to toxicity.

Clinical considerations

Consider the following when reviewing medicine interactions with methotrexate:

  • presence of active infection
  • whether the new medicine can impact the kidney, liver or cause blood disorders
  • if an increase in monitoring is required as part of interaction management
  • the duration of the new medicine

Review the interaction on a case-by-case basis as the management advice may vary for different people.

The person taking methotrexate should be counselled to ask about medicine interactions before taking other prescribed medicines or buying medicines over-the-counter.

Advice for specific medicines with methotrexate

The SPS interactions advice has been developed from published evidence, literature reviews and expert opinion, where needed. It includes commonly asked questions on medicine interactions and is not comprehensive for all potential interactions with methotrexate.

Further information

Drug interactions: resources to support answering questions signposts to common resources for checking medicine interactions.

Using folic acid with methotrexate in rheumatoid arthritis provides information on administration and dosing.

Primary care healthcare professionals in England can seek further advice from our Medicines Advice service if the information is not available on the SPS website, or if the clinical scenario is complex.

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