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Sulfasalazine (Azulfidine EN-tabs)

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.3,4,5

What are the possible side effects of sulfasalazine?

Common side effects associated with sulfasalazine include6:

  • 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 immediately6:

  • 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.

Things to note about sulfasalazine

Before taking sulfasalazine, tell your doctor if you5:

    • 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/sup>

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 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

Dosing information

Sulfasalazine comes in a 500-mg tablet for oral use. It typically starts at a dose of 500 mg per day and is increased by 500 mg every week, while monitoring for side effects, until a daily target dose (this is determined by your weight, approximately 40 mg/kg) is reached. For most adult patients with RA, the final daily dose ranges from 2000-3000 mg (2-3 grams).

If you have stomach problems when taking this medicine, you can divide up the full dose evenly across the day, or you can take a special enteric-coated form of the medication (Azulfidine EN-tabs). To help prevent stomach upset, take sulfasalazine with food, followed by a full glass of water.3,6

It typically takes 1 to 3 months before you notice improvements in RA symptoms after starting sulfasalazine, although some patients experience relief after a few weeks on the medication.6,7

Written by: Sara Finkelstein | Last reviewed: September 2019.
  1. Sulfasalazine. American College of Rheumatology. Available at: Accessed May 19, 2018
  2. Azulfidine EN-tabs®. Pfizer. Pharmacia & Upjohn Co. New York, NY. Revised December 2012. Accessed May 17, 2018.
  3. Deane KD, West SG. Other traditional disease-modifying anti-rheumatic drugs: monotherapy and combination therapy. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatoid Arthritis. Philadelphia, Penn: Mosby Elsevier; 2009:325-336.
  4. Gibofsky A. Comparative effectiveness of current treatments for rheumatoid arthritis. Am J Manag Care 2012;18:S303-14.
  5. Carolina Negrei, Violeta Bojinca, Andra Balanescu, et al. Management of rheumatoid arthritis: Impact and risks of various therapeutic approaches. Exp Ther Med. 2016 Apr; 11(4): 1177–1183. Published online 2016 Feb 2. doi: 10.3892/etm.2016.3045 Accessed May 18, 2018.
  6. Sulfasalazine. MedLine Plus. US National Library of Medicine. Bethesda, MD. Revised May 15, 2017. Accessed May 17, 2018.
  7. Salazopyrin® En-tabs. Pfizer Limited, Sandwich, Kent, UK. Last revised 12/2016. Accessed May 19, 2018.