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Review of photosensitivity reactions with methotrexate

Methotrexate is an immunosuppressant medicine that is used to treat inflammatory conditions such as rheumatoid arthritis, psoriasis, and Crohns disease. It is also used as a cancer treatment.

The MHRA has recently received a Coroners report following a case of a photosensitivity reaction in a patient on methotrexate. This reaction was found to have contributed to their death by secondary infection. As a result of this, we have reviewed the information available to healthcare professionals and patients regarding these reactions and sought advice from the Pharmacovigilance Expert Advisory Group (PEAG) of the Commission on Human Medicines.

Photosensitivity reactions are established side effects of methotrexate treatment and are currently listed in the product information, including the Patient Information Leaflet. However, the PEAG was concerned that it is not a well-known side effect and many patients may not be aware of the additional risks of sun exposure during methotrexate treatment.

Prescribers and pharmacists are reminded to inform patients of the risk of photosensitivity reactions and to advise them to use a product with a high sun protection factor and clothing that covers the skin when in the sun. We are working with Marketing Authorisation Holders of methotrexate medicines to provide updates to the product information as appropriate.

Characteristics of reactions

Photosensitivity reactions often look and feel like sunburn. They can leave sun-exposed skin with a rash, redness, swelling, blisters, red bumps or oozing lesions. Severe cases can cause secondary skin infection. Photosensitivity reactions fall into two categories; phototoxic reactions and photoallergic reactions.

In phototoxic reactions, a drug is activated by exposure to UV light and causes damage to the skin that can look and feel like a sunburn or a rash. These reactions can happen within minutes or after hours of exposure and are usually limited to the skin that has been exposed.

Photoallergic reactions occur when UV rays interact with the ingredients in medicines or other products applied directly to the skin. The bodys immune system recognizes changes caused by sun exposure as a foreign threat. The body produces antibodies and attacks, causing a reaction.^{[footnote 1] [footnote 2]}

These reactions are distinct from recall reactions where radiation-induced dermatitis and sunburn can reappear on re-exposure to radiation and sunlight while on methotrexate therapy.

Report suspected reactions on a Yellow Card

Please continue to report suspected adverse drug reactions to the Yellow Card scheme. Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:

• the Yellow Card website
• the Yellow Card app; download from the Apple App Store or Google Play Store
• some clinical IT systems for healthcare professionals (EMIS, SystmOne, Vision, MiDatabank, and Ulysses)

When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset timing, treatment dates, and product brand name.

Article citation: Drug Safety Update volume 17, issue 1: August 2023: 2.