Sulfasalazine (Azulfidine EN-tabs)

Reviewed by: HU Medical Review Board | Last reviewed: May 2023

Sulfasalazine is a disease-modifying anti-rheumatic drug (DMARD) used for the treatment of adults and children over 6 with RA who have not responded to non-steroidal anti-inflammatory drugs (NSAIDs). DMARDS decrease the pain and swelling of inflammatory arthritis and may also prevent damage to joints, which can reduce the risk of long-term loss of function.

A member of a class of drugs called sulfa drugs, sulfasalazine was first used in patients with RA about 70 years ago when the disease was thought to result from a bacterial infection.1

Brand names for sulfasalazine include Azulfidine and Azulfidine EN-tabs; sulfasalazine is also available in generic forms.

What are the ingredients in sulfasalazine?

The active ingredient in Azulfidine EN-tabs is sulfasalazine, formulated in an enteric-coated, delayed-release tablet. The tablets are coated in a thin film so the medicine does not dissolve in the stomach and irritate the stomach lining.1

How does sulfasalazine work?

Sulfasalazine is made up of two components, 5-aminosalicylic acid and a sulfa antibiotic, called sulfapyridine. Researchers partially understand how the drug works against RA and other inflammatory diseases. It seems to interfere with the production of key immune system factors, like tumor necrosis factor, interleukin 1 and 6, and certain antibodies, that lead to inflammation and subsequent tissue damage.3-5

What are the possible side effects?

Common side effects associated with sulfasalazine include:6

  • Headache
  • Diarrhea
  • Appetite loss
  • Stomach upset and pain
  • Vomiting

If you experience any of the following symptoms while taking sulfasalazine, stop taking the medication and call your doctor immediately:6

  • Skin rash
  • Hives
  • Itching
  • Swelling
  • Fever
  • Sore throat
  • Muscle or joint pain
  • Difficulty swallowing
  • Fatigue or tiredness
  • Weakness
  • Pale or yellow skin
  • Unusual bleeding or bruising

These are not all the possible side effects of sulfasalazine. Talk to your doctor about what to expect when taking sulfasalazine. You also should call your doctor if you have any changes that concern you when taking sulfasalazine.

Other things to know

Before taking sulfasalazine, tell your doctor if you:5

    • Are allergic to sulfasalazine or any of its components, including sulfa drugs
    • Have or have ever had asthma
    • Have or have ever had kidney or liver disease
    • Have or have ever had porphyria or other blood problems
    • Have or have ever had blockage in your intestines or urinary tract
    • Are pregnant or plan to become pregnant
    • Are breastfeeding

Patients who receive sulfasalazine should have complete blood count and liver function tests before starting treatment, every 1 to 2 weeks during the first 3 months of therapy, every 2 to 4 weeks during the second 3 months of therapy, and then every 3 months once you establish a regular dose.13

It is important to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunscreen, and sunglasses, as sulfasalazine may make your skin sensitive to the sun. It also causes temporary infertility in males, but this is reversible once the medicine is stopped. It can cause your urine or skin to turn yellow-orange, but this is a harmless effect.6

Sulfasalazine should be used with caution in patients who have liver or kidney damage, disorders of the blood, bronchial asthma, or those with intestinal or urinary blockages. Signs of serious blood disorders or liver toxicity include fever, pallor, sore throat, purpura or jaundice. If you experience these symptoms, it is important to seek immediate medical attention.2

Some patients experience life-threatening allergies to sulfasalazine, so sulfasalazine should be stopped at the first signs of an allergic reaction. This includes skin rash, hives, mucosal lesions, fever, or enlargement of lymph nodes.2

Certain drugs do not mix well with sulfasalazine. Before beginning treatment for RA, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.2,7

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