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Arthritis health centre

Taking sulfasalazine, hydroxychloroquine, and methotrexate together

BMJ Group Medical Reference


This information is for people who have rheumatoid arthritis. It tells you about taking sulfasalazine, hydroxychloroquine, and methotrexate together. It is based on the best and most up-to-date research.

Does it work?

Yes. There's good evidence that this combination of drugs can be helpful, if other treatments haven't worked.

What is it?

Methotrexate and sulfasalazine belong to a group of drugs used to help slow down rheumatoid arthritis. These drugs are called disease-modifying anti-rheumatic drugs (DMARDs for short). They also help to reduce the pain and swelling in your joints.

Hydroxychloroquine is an anti-malarial drug. Antimalarial drugs are also used to reduce the pain and swelling in your joints.

To find out more about the individual drugs, see our information on methotrexate, sulfasalazine and antimalarials. You take them as tablets.

You'll only have this combination of three drugs if other drugs haven't helped.

How can it help?

Taking these three drugs together can reduce the pain and swelling in your joints, and help if your joints feel stiff first thing in the morning.

This may make it easier for you to do things like going shopping, doing the housework, having sex, seeing your friends and doing other things you enjoy.

Studies have compared taking the three drugs together with taking them separately, or taking two of the drugs together. The studies showed that taking the three drugs together worked for more people. [49] [50]

One study compared people who started off on all three drugs, with people who started on one then had the other two added when their symptoms got worse. The study showed that, after a year, both groups of patients were doing equally well. So adding treatments when you need them works at least as well as starting off with all of them. [51]

How does it work?

Scientists are not sure exactly how these three drugs work. They seem to affect the immune system. Usually, your immune system protects you from infection. But if you have rheumatoid arthritis, the immune system attacks the lining of the joints.

Can it be harmful?

Each of these drugs can have side effects. To learn more, see our information on taking sulfasalazine, hydroxychloroquine, and methotrexate separately.

The most common side effects for sulfasalazine are:

  • Diarrhoea

  • Stomach pain

  • Loss of appetite

  • Vomiting

  • Skin rash

  • Itching.

The most common side effects for hydroxychloroquine are:

  • Nausea

  • Diarrhoea or constipation

  • Headache and dizziness

  • Loss of appetite

  • Skin rash

  • Blurred vision.

The most common side effects for methotrexate are:

  • Hair that's thin or brittle

  • Acne or blisters on the skin

  • Loss of appetite or weight

  • Blisters in the mouth

  • Tiredness.

But in the research we looked at, taking the drugs together didn't seem to increase the side effects much. People were no more likely to stop taking the combined treatment because of side effects, than to stop taking one of the treatments alone. [50] [49]

How good is the research on taking sulfasalazine, hydroxychloroquine, and methotrexate together?

We found two good-quality studies looking at this combination of drugs. [50] [49] The studies included 273 people in total. Some people took all three drugs, while others took one or two of the drugs.

In both studies, more than 7 in 10 people taking all three drugs had a big improvement in pain and swelling in their joints. The results weren't as good for the people who took the drugs separately.


For references related to Rheumatoid arthritis click here.
Last Updated: August 15, 2013
This information does not replace medical advice.  If you are concerned you might have a medical problem please ask your Boots pharmacy team in your local Boots store, or see your doctor.

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