Published: 6 March 2025
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Spotlight on weekly methotrexate
Published: 6 March 2025
Prescriber Update 46(1): 2–4
March 2025
This article reviews the safety profile of weekly methotrexate, an immunosuppressant used to treat psoriasis and rheumatoid arthritis.1
Methotrexate safety profile1
Methotrexate may cause significant adverse drug reactions and toxicity in many organ systems (Table 1).
For psoriasis and rheumatoid arthritis, the importance of once weekly dosing should be emphasised. Mistaken daily use increases the risk of life-threatening or fatal toxicity. The risk is higher at doses greater than 20mg per week.
Table 1: Adverse drug reactions and toxicity associated with methotrexate*
| Organ system | Examples of adverse reactions/toxicity |
|---|---|
| Blood and lymphatic | Anaemia, pancytopenia, leucopoenia, neutropenia, thrombocytopenia, bleeding |
| Immune | Infections, including fatal sepsis |
| Gastrointestinal | Vomiting, diarrhoea, stomatitis, gingivitis, enteritis, hepatotoxicity, hepatic failure |
| Pulmonary | Interstitial pneumonitis, pleural effusion, fibrosis |
| Skin and subcutaneous disorders | Stevens-Johnson Syndrome, toxic epidermal necrolysis, erythema multiforme, photosensitivity, increased risk of skin cancer |
| Renal | Severe nephropathy, renal failure |
| Reproductive | Defective oogenesis or spermatogenesis, congenital malformations, intrauterine growth restriction, spontaneous abortion |
* Not an exhaustive list. Refer to methotrexate data sheets for known side effects.
Source: Rex Medical Ltd. 2024. Trexate New Zealand Data Sheet 27 September 2024. URL: www.medsafe.govt.nz/profs/Datasheet/t/trexatetab.pdf (accessed 15 January 2025).
Prescribing considerations
Methotrexate should only be prescribed by physicians with expertise in the use of methotrexate and a full understanding of the risks of methotrexate therapy.1
Other considerations are outlined below. Refer to the data sheets for full prescribing information.
Before beginning treatment1
Perform a full blood count, liver and renal function tests, and take a chest x-ray. Evaluate for personal and family history of liver disease, personal history of alcohol use or gastrointestinal ulcerative conditions.
If clinically indicated, screen for tuberculosis, hepatitis B and C, and perform a pregnancy test.
Monitor during treatment
Monitor blood count, liver and renal function throughout treatment.1
More frequent monitoring may be required during the initial phase of treatment, when the dose is increased, during episodes of changes to renal function, use of interacting medicines or in at-risk patients, such as the elderly.1
Folic acid or folinic acid may be used with methotrexate to reduce the risk of gastrointestinal side effects.1
Advise patients, family and/or caregivers to seek medical advice immediately if signs or symptoms of methotrexate toxicity occur, including sore throat, bruising, mouth ulcers, nausea, vomiting, abdominal discomfort, dark urine, shortness of breath or cough.1
Monitor patients regularly for treatment response and toxicity and manage accordingly.1
Importance of once weekly dosing
When methotrexate is taken as a single dose once weekly, ensure that patients, family and/or caregivers understand the correct number of tablets to take and what day of the week to take them.1 Inform patients of what to do if they have missed a dose.2
Patients of childbearing potential1
Methotrexate is teratogenic and is contraindicated in pregnancy.
If either partner is receiving methotrexate, pregnancy should be avoided and effective contraception used during treatment and after discontinuation (for at least 3 months after treatment for males and at least 6 months for females).
Make sure that patients understand the need to plan any pregnancies.
Methotrexate is also contraindicated in breastfeeding.
New Zealand case reports
From 1 January 2014 to 31 December 2024, there were 101 case reports for methotrexate where the reported indication was for psoriasis or arthritis conditions. Of these 101 reports, 89 were reported as serious. Where demographic information was reported, the majority of reports were in older adults (median age 66 years), European/Other ethnicity (71 reports) and women (71 reports).
The most frequently reported adverse reactions were nausea (12 reports), pancytopenia (10), pneumonitis (10), mouth ulceration (7), interstitial lung disease (6), malaise (5), thrombocytopenia (5), headache (4), hepatic enzyme increased (4), neutropenia (4) and sepsis (4).
More information
- See the methotrexate data sheets and consumer medicine information (CMI): Search for a data sheet or CMI.
- Healthify has information for consumers about methotrexate: Methotrexate tablets for inflammatory conditions.
- Medsafe has published a Prescriber Update article about interactions with low-dose methotrexate.
- Refer to local clinical guidelines for information on methotrexate prescribing and monitoring.
References
- Rex Medical Ltd. 2024. Trexate New Zealand Data Sheet 27 September 2024. URL: www.medsafe.govt.nz/profs/Datasheet/t/trexatetab.pdf (accessed 15 January 2025).
- New Zealand Formulary (NZF). 2025. NZF v152: Methotrexate (autoimmune conditions) 1 February 2025. URL: nzf.org.nz/nzf_71530 (accessed 12 February 2025).
