Methotrexate: advise patients to take precautions in the sun to avoid photosensitivity reactions

Photosensitivity reactions are known side effects of methotrexate treatment and can be severe. Patients should be advised to take precautions to protect their skin in the sun.

From:
Medicines and Healthcare products Regulatory Agency
Published
30 August 2023
Therapeutic area:
Cancer, Dermatology, Rheumatology

Advice for healthcare professionals:

  • photosensitivity reactions (which include phototoxicity, where 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) are known side effects of methotrexate treatment and can occur with both low-dose and high-dose treatment
  • reactions manifest as severe sunburn such as rashes with papules or blistering, with some patients reporting swelling; rarely, photosensitivity reactions have contributed to deaths from secondary infections
  • healthcare professionals, including those prescribing and dispensing methotrexate, should remind patients to take precautions to protect themselves from the sun and UV rays
  • report suspected adverse drug reactions associated with methotrexate on a Yellow Card

Advice for healthcare professionals to provide to patients and caregivers:

  • methotrexate treatment may make your skin more sensitive to the sun
  • sun exposure during methotrexate treatment could cause very severe reactions that look and feel like sunburn
  • avoid exposure to intense sunlight (especially between 11 am and 3 pm) or to UV rays (for example, using sunbeds or tanning equipment) while taking methotrexate
  • use a sun protection product with a high protection factor when exposed to the sun
  • wear a hat and clothes that cover your arms and legs when in the sun
  • talk to a healthcare professional if you are worried about a skin reaction you have had while taking methotrexate

Review of photosensitivity reactions with methotrexate

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

The MHRA has recently received a Coroner’s 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 body’s 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:

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.

  1. Skin Cancer Foundation. Photosensitivity & Your Skin. Accessed July 2023. ↩

  2. Glatz M, Hofbauer GFL. Phototoxic and photoallergic cutaneous drug reactions. Chemical Immunology and Allergy 2012; volume 97: pages 167 to 179. ↩

Updates to this page

Published 30 August 2023
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