For many people with rheumatoid arthritis, psoriatic arthritis and other inflammatory conditions, one day a week is “methotrexate day”. And for some, it comes with a hangover: feeling sick, a headache and a heavy tiredness that can wipe out a day or two.
Methotrexate helps to control the overactive immune system that causes joint damage in these conditions, so it's worth persevering. The good news is that side effects can often be eased. You don't have to just put up with them.
Please note
This page is general information, not medical advice. Never change your dose, the time you take it or the type of methotrexate without talking to your rheumatology team first.
Why methotrexate day can feel rough
Many people say methotrexate upsets their stomach or makes them feel sick (Arthritis UK, n.d.). When you swallow a tablet, the level in your blood peaks within 1 to 2 hours, and most of it leaves your body through your kidneys within a day (Mercury Pharmaceuticals, n.d.).
Your team will usually prescribe folic acid to help reduce side effects (Arthritis UK, n.d.). But there is more you can talk to them about.
What to ask your rheumatology team about
| Option | What the evidence says | Worth asking about if |
|---|---|---|
| Simple meals | You can take tablets before or after food (NHS, 2023b). If you feel sick, the NHS suggests simple meals, not rich or spicy food (NHS, 2023d). | Your stomach is unsettled on methotrexate day |
| An evening dose | Blood levels peak 1 to 2 hours after a tablet (Mercury Pharmaceuticals, n.d.), so some people prefer to take it before bed. There is little research on timing, so agree it with your team first. | Sickness or tiredness wipes out your day |
| Switching to an injection | Injections go under the skin, often with a pre-filled pen you can use at home after training (NHS, 2023b). They skip the stomach, but they don't suit everyone: in one review, more people starting injections stopped because of side effects (Visser and van der Heijde, 2009). | Tablets still make you feel unwell, or aren't working well enough |
| Splitting the dose | Research looks at whether splitting helps the drug work, not at easing sickness. One trial found slightly more stomach upset with a split dose (Prasad et al., 2025). | Only if your consultant suggests it |
Key insight: the folic acid rule
Don't take folic acid on the same day as methotrexate, as it can stop your medicine working properly. Most people take it the day after (NHS, 2023b). And don't take extra supplements containing folic acid if it is already prescribed (NHS, 2023e).
If you are being sick, the NHS suggests taking small, frequent sips of water to avoid dehydration (NHS, 2023d). Tell your team if sickness carries on, as there are other options to try (Arthritis UK, n.d.).
Safety essentials
| Topic | What to know |
|---|---|
| Once a week | Take it on the same day each week. If you take more than your dose, or take it daily instead of weekly, contact 111 for advice now (NHS, 2023b). |
| Missed dose | Take it as soon as you remember, the next day or the day after. If it's more than 2 days late, contact your doctor or clinic (NHS, 2023b). |
| Blood tests | Every 1 to 2 weeks at first, then every 2 to 3 months once your dose is stable (NHS, 2023b). |
| Alcohol | Stay within 14 units a week, because alcohol and methotrexate can both affect your liver (Arthritis UK, n.d.). |
| Other medicines | Check with a pharmacist first. These include ibuprofen and other anti-inflammatory painkillers, cough and cold remedies, the antibiotics trimethoprim and co-trimoxazole, and omeprazole (NHS, 2023e). |
| Vaccines | Have the vaccines you're invited for, but tell the person giving them that you take methotrexate, as some may not be suitable (NHS, 2023a). |
| Pregnancy and fertility | Methotrexate can cause birth defects, and it may damage sperm. Speak to your doctor before trying for a baby, whatever your gender (NHS, 2023c). |
Get help now
Contact your doctor or call 111 straight away if you have a high temperature or feel hot, cold or shivery, a sore throat, unexplained bruising or bleeding, or a persistent cough, chest pain or breathlessness (NHS, 2023d). Call 999 for a serious allergic reaction.
Keep it routine
- Pick a day that suits your week and stick to it. Set a phone reminder or use a pill organiser.
- Carry your methotrexate patient card, and show it to anyone who prescribes or sells you medicines (NHS, 2023e).
- Keep a note of how you feel each week, so you can show your team what is and isn't working.
Trusted information
- Arthritis UK: methotrexate, plus free information booklets to download or order.
- NHS: methotrexate, including side effects, other medicines and pregnancy.
- On this blog: taking your medicines as prescribed, the pharmacy fear factor and our guide to JIA for parents.
The Zero Jargon bottom line
A methotrexate hangover is common, but it isn't something you have to live with. Keep a note of how you feel, and ask your team about food, timing, folic acid and injections. Small changes, agreed with your team, can give you your week back.
References
Arthritis UK (n.d.) Methotrexate. Available at: https://www.arthritis-uk.org/information-and-support/understanding-arthritis/arthritis-treatments/drugs/methotrexate/ (Accessed: 27 September 2026).
Mercury Pharmaceuticals (n.d.) Methotrexate 2.5 mg tablets: summary of product characteristics. Electronic medicines compendium. Available at: https://www.medicines.org.uk/emc/product/511/smpc (Accessed: 27 September 2026).
NHS (2023a) Common questions about methotrexate. Available at: https://www.nhs.uk/medicines/methotrexate/common-questions-about-methotrexate/ (Accessed: 27 September 2026).
NHS (2023b) How and when to take methotrexate. Available at: https://www.nhs.uk/medicines/methotrexate/how-and-when-to-take-methotrexate/ (Accessed: 27 September 2026).
NHS (2023c) Pregnancy, breastfeeding and fertility while taking methotrexate. Available at: https://www.nhs.uk/medicines/methotrexate/pregnancy-breastfeeding-and-fertility-while-taking-methotrexate/ (Accessed: 27 September 2026).
NHS (2023d) Side effects of methotrexate. Available at: https://www.nhs.uk/medicines/methotrexate/side-effects-of-methotrexate/ (Accessed: 27 September 2026).
NHS (2023e) Taking methotrexate with other medicines and herbal supplements. Available at: https://www.nhs.uk/medicines/methotrexate/taking-methotrexate-with-other-medicines-and-herbal-supplements/ (Accessed: 27 September 2026).
Prasad, C.B., Dhir, V., Gupta, R. et al. (2025) ‘Split vs single-dose oral methotrexate in rheumatoid arthritis: a randomized controlled trial (SMART study)’, Clinical Rheumatology, 44(10), pp. 3869–3879. Available at: https://doi.org/10.1007/s10067-025-07646-y (Accessed: 27 September 2026).
Visser, K. and van der Heijde, D. (2009) ‘Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature’, Annals of the Rheumatic Diseases, 68(7), pp. 1094–1099. Available at: https://doi.org/10.1136/ard.2008.092668 (Accessed: 27 September 2026).
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Important medical disclaimer
The content provided in this blog post is for educational and informational purposes only and does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your GP, psychiatrist or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. Never start, stop or change a prescribed medicine without speaking to your prescriber first.
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