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Sulfasalazine (Azulfidine)

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Sulfasalazine (Azulfidine) is considered a disease-modifying anti-rheumatic drug (DMARD). Sulfasalazine reduces inflammation and is used in the treatment of rheumatoid arthritis (RA), inflammatory bowel disease, and some other autoimmune conditions. You should not take it if you have a sulfa allergy.

How to Take It

Sulfasalazine comes in a 500 mg tablet and should be taken with food and a full glass of water to avoid an upset stomach. The medication is often started at a lower dose when treating RA to prevent side effects, typically 1 to 2 tablets a day. After the first week, the dose may be slowly increased to the usual dosage of 2 or 3 tablets twice a day. An enteric-coated preparation is available that may lessen some of the side effects, particularly stomach upset. This form of sulfasalazine should not be crushed or chewed. It usually takes between 2 to 3 months to notice any improvement in RA symptoms after starting sulfasalazine.

Side Effects

In general sulfasalazine is well-tolerated. The most common side effects are headache, nausea, and abdominal discomfort, which occur early during treatment. These may improve with time and are often avoided by slowly increasing from a low starting dose. Sun sensitivity of the skin can also be a side effect. Those on sulfasalazine should use sunscreen when outdoors and avoid prolonged exposure to sunlight. Some people will develop orange colored urine. This should not cause alarm. It is usually harmless and goes away after medication is stopped. In some cases, sulfasalazine may reduce the number of blood cells, or may cause abnormal liver tests. Your doctor will perform blood tests regularly to check these. Sulfasalazine can cause an allergic reaction that varies from mild (skin rash) to more severe (fevers, abnormal liver tests). Sulfasalazine can lower sperm counts but this effect is reversible when the medication is discontinued.

Tell Your Rheumatology Provider

Sulfasalazine may interfere with warfarin (Coumadin), cyclosporine or digoxin, so dose adjustments may be needed if these medications are taken together. Sulfasalazine increases the risk for liver injury if given with the drug isoniazid (INH), a drug for tuberculosis and may increase the risk for low blood sugar in patients taking certain medications for diabetes such as glimepiride (Amaryl), glyburide (Diabeta, Micronase, Glynase) and glipizide (Glucotrol). Sulfasalazine is safe for pregnancy and breastfeeding. Tell your doctor if you have ever had any unusual or allergic reaction to other medicines that are chemically related to sulfa drugs.

Updated February 2024 by Karmela Kim Chan, MD, and reviewed by the American College of Rheumatology Committee on Communications and Marketing.

This information is provided for general education only. Individuals should consult a qualified health care provider for professional medical advice, diagnosis, and treatment of a medical or health condition.

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