What is methotrexate?

Methotrexate (brand name Methoblastin or injectable methotrexate (Hospira, Methacord, Methotrexate Accord & Trexject) is a well-established, effective treatment for several different types of inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease, SLE (Systemic Lupus Erythematosus) and severe psoriasis. It may also be used for other conditions.

It can reduce damage to joints, skin and other tissues so it belongs to the group of medicines called disease modifying antirheumatic drugs (DMARDS). It is not a painkiller.

Low dose methotrexate (5mg-30mg once per week) has been used to treat rheumatoid arthritis for more than 25 years. Most, but not all, patients will benefit from this medicine. It is also used at very high doses (1000mg-5000mg a day) to treat some cancers.

What benefit can you expect from your treatment?

Methotrexate has been shown to prolong life and can reduce the risk of heart disease in rheumatoid arthritis.

It may be 4 to 12 weeks after reaching the best dose for your condition before you notice any benefits. Many of the conditions that are treated with methotrexate are long term and methotrexate may need to be taken for several years or in some people, indefinitely. Some other DMARDs are taken with methotrexate for added benefit.

How is methotrexate taken?

Methotrexate may be taken by mouth as a tablet or given by injection either into the muscle or under the skin (subcutaneously). For more information on the injections see the Self-injecting low dose methotrexate infosheet.

Methotrexate is taken ONCE A WEEK, on the same day each week. If you are taking the tablets, it is a good idea to specify the day of the week that you will take your tablets to avoid making mistakes.

Methotrexate tablets are best taken on an empty stomach. However if nausea is a problem, taking them at mealtime can help to reduce this side effect and does not reduce the benefits too much.

What is the dosage?

Tablets come in 2.5mg or 10mg strengths. If you have two strengths ensure you CHECK THE STRENGTH each time you take it. Treatment may start low at 5mg or 10mg a week, increasing to an average dose of 20mg a week, and sometimes 30mg/week.

The dose is usually taken all at once on a single day. It may be divided into separate doses taken during that day if necessary.

If you stop methotrexate treatment for more than a few weeks there is a risk that your condition may worsen. Continue with your treatment unless advised by your doctor or unless side effects develop.

If you have an illness that makes you unwell enough to change plans for the day (e.g. gastroenteritis or fever), it is reasonable to miss the weekly dose until you have recovered.

Can other medicines be taken with methotrexate?

In order to reduce side effects, it is recommended that you also take folic acid or folinic acid. Your doctor will explain how much of the folic/folinic acid to take and when to take it.

Methotrexate is often taken in combination with other arthritis medicines, including:

• other DMARDs
• biological DMARDs ( these act on natural substances in the body that contribute to inflammation and joint damage)
• steroid medicines such as prednisolone or cortisone injections into the joint
• anti-inflammatory medicines (NSAIDs) such as naproxen (Naprosyn) or ibuprofen (Brufen/Nurofen)
• simple pain medicines such as paracetamol

Are there any side effects?

Some experience side effects so tell your doctor if you are concerned about possible side effects.

A reduction in dose may minimise these so you may be able to continue it. Your doctor will advise on any dose changes that are necessary.

Most common possible side effects: (Folic or Folinic acid helps to reduce side-effects)

• Fatigue, mental clouding, nausea, vomiting or diarrohea. These can be reduced if methotrexate is taken with food or in the Anti-nausea tablets can be used if needed.
• Mouth ulcers

Less common or rare possible side effects:

There are some rare but potentially serious side effects with methotrexate:

• Skin dryness, a variety of skin rashes and increased sensitivity to the sun may also occur. You should wear sunscreen and a hat when out in the sun.
• Some also experience a temporary increase in muscle and joint pain after taking the weekly dose
• Blood counts: Methotrexate may cause a drop in the number of white blood cells, which are needed to fight infection. It can also cause a drop in the number of platelets, which help to stop bleeding.
  • Regular blood tests aim to pick these problems up early if they occur.
  • If you develop a sore mouth, mouth ulcers, easy bruising, nosebleeds, bleeding gums, breathlessness, infection or fever tell your doctor straight away.
• Hair thinning: This may occur rarely. It is not permanent and hair will grow back when the medicine is stopped.
• Liver: Methotrexate can inflame the liver and this can be seen on blood testing.   Regular blood tests aim to pick this up early if it The dose of methotrexate may have to be reduced or stopped if problems occur. Liver problems may be increased when methotrexate is combined with other medicines or with heavy alcohol use (see Alcohol overleaf).
• Lungs: Methotrexate can cause inflammation of the This may be more likely if leflunomide is being taken at the same time. The problem may develop quickly, so if you have a sudden onset of breathing difficulties seek medical attention as soon as possible. It may also develop with symptoms such as a dry cough.
• Nodule formations: Some people with rheumatoid arthritis develop nodules on their elbows or other pressure points. In some cases methotrexate may increase this.
• Cancer: see below.

Long term side effects:

Methotrexate may be taken for long periods (more than 25 years). The following are rare but possible long-term issues:

• Liver: Very rare cases of increased fibrous tissue in the liver have been reported after long-term treatment. This risk is increased when combined with alcohol. Regular monitoring can minimise the risk of this occurring.
• Cancer: People who have rheumatoid arthritis and other similar inflammatory conditions have an increased risk of lymphoma (a lymph node cancer). It is not clear whether methotrexate increases this risk further but any additional risk is likely to be very small. Methotrexate may also reduce the risk of these cancers by controlling the For general cancer prevention, stopping smoking is recommended. An annual skin check to detect any early skin cancer is also recommended.
• Fertility: Methotrexate does not affect a person’s ability to have children in the long term. See also Precautions.

More information about possible side effects:

Information that comes with your methotrexate medicine describes in detail potential serious side effects that may occur with methotrexate. Many of those side effects relate to high dose methotrexate used for the treatment of cancer. These may not be applicable to the much lower doses that are prescribed for the treatment of rheumatoid arthritis.

What precautions are necessary?

Blood tests:

• As methotrexate may affect the liver and blood cells, you MUST have regular blood tests during your treatment. This is very important, as you may not get symptoms with some of these problems.
• You will need to have full blood counts and liver function tests every 2 to 4 weeks for the first few months of treatment and then every 1 to 3 months after that

Risk of infections:

Because your immune system may be depressed, there is an increased risk of developing some infections, especially Herpes zoster (chicken pox and shingles).

You should try to avoid contact with people who have these infections. If you have an infection or persistent fever, tell your doctor straight away.

Use with other medicines:

Methotrexate can interact with other medicines. You should tell your doctor (including your GP, rheumatologist and others) about all medicines you are taking or plan to take. This includes over the counter, herbal or naturopathic medicines. You should also mention your treatment when you see other health professionals.

• Methotrexate can be taken safely with anti- inflammatory drugs (NSAIDs), as long as your kidney function is
• Antibiotics containing trimethoprim (e.g. Bactrim, Septrim or Triprim) can cause problems when taken with methotrexate. If you are prescribed any of these medications you must tell the doctor you are taking methotrexate.
• Most vaccines can be given safely. Current recommendations are that low dose methotrexate (0.4mg/kg per week) is not a contraindication to live vaccines, such as Zostavax, MMR (measles, mumps and rubella), oral polio or yellow fever but such live vaccines should be avoided at higher doses of methotrexate.
• Pneumovax and yearly flu vaccinations are safe and recommended to reduce your risk of those infections.
• Talk with your rheumatologist before receiving any vaccines.

Use with alcohol:

• Alcohol increases the risk of liver damage while taking methotrexate. Methotrexate usage in heavy drinkers has been associated with cirrhosis of the liver.
• It is not known precisely what level of drinking is safe when on methotrexate, however there is general agreement that 1 to 2 standard drinks taken once or twice a week is unlikely to cause a problem.
• Drinking more than 4 standard drinks on one occasion, even if infrequently, is strongly discouraged.

Surgery:

• If low dose once weekly methotrexate is continued during surgery there seems to be no change in wound healing or increased infection.

Use in pregnancy and breastfeeding:

Read the ARA’s Notes on Prescribing Medications for Rheumatic Diseases in Pregnancy.

• Methotrexate should not be taken during pregnancy as it can cause miscarriage or foetal deformity. It should also not be taken when breastfeeding.
• Women of child-bearing age should use effective contraception while taking methotrexate.
• Women planning to become pregnant should stop taking methotrexate 3 months before attempting to conceive.
• Based on recent studies low-dose methotrexate seems safe when the father is taking methotrexate.
• Methotrexate does not affect a person’s ability to have children in the long term.

How to store methotrexate:

• Store methotrexate in a cool, dry place, away from direct heat and light (e.g. not in the bathroom)
• Keep out of reach of children.

This information has been produced by the Australian Rheumatology Association (ARA) to help you understand the medicine that has been prescribed for you. Please read it carefully and discuss it with your doctor. The information in this sheet has been obtained from various sources and has been reviewed by the ARA. It is intended as an educational aid and does not cover all possible uses, actions, precautions, side effects, or interactions of the medicines mentioned. This information is not intended as medical advice for individual problems nor for making an individual assessment of the risks and benefits of taking a particular medicine. It can be reproduced in its entirety but cannot be altered without permission from the ARA. The NHMRC publication: How to present the evidence for consumers: preparation of consumer publications (2000) was used as a guide in developing this publication.