Sulfasalazine (Azulfidine EN-tabs)

Reviewed by: HU Medical Review Board | Last reviewed: March 2022 | Last updated: April 2022

Sulfasalazine is a disease-modifying anti-rheumatic drug (DMARD) indicated 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 of sulfasalazine?

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

This is not an exhaustive list of all potential side effects of sulfasalazine. For more information, consult your doctor or healthcare provider. If you notice any new or worsening side effects, contact your doctor or healthcare provider immediately. For more information on adverse effects, see additional warnings for sulfasalazine.

Things to know about sulfasalazine

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, so you should tell your doctor about any other medications or supplements you are taking. These include the blood thinner warfarin (Coumadin), cyclosporine, and digoxin. It does not mix well with certain antibiotics for urinary tract infections as well as others given for RA (methotrexate) or to suppress the body’s immune response. If sulfasalazine is given with the tuberculosis drug isoniazid, it may increase the risk of liver damage. If given with diabetes medications, including glimepiride (Amaryl), glyburide (Diabeta, Micronase, Glynase), and glipizide (Glucotrol), it may increase the risk for low blood sugar.2,7

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