Sulfasalazine (Azulfidine)

Pill bottle with pills

Sulfasalazine (Azulfidine) is considered a disease-modifying anti-rheumatic drug (DMARD). It can decrease the pain and swelling of arthritis, prevent joint damage, and reduce the risk of long-term disability. Sulfasalazine is in a type of sulfa drug. You should not take it if you have a sulfa allergy. Sulfasalazine is used in the treatment of rheumatoid arthritis (RA), inflammatory bowel disease, and some other autoimmune conditions. It works to lower inflammation in the body.

How to Take It

Sulfasalazine comes in a 500mg tablet and should be taken with food and a full glass of water to avoid an upset stomach. The medication is often started at low doses when treating RA to prevent side effects, typically one - two tablets a day. After the first week, the dose may be slowly increased to the usual dosage of two tablets (1g) twice a day. This dose can be increased to up to six pills (3g) a day in some situations. An Enteric-coated (or stomach-coated) preparation is available that may lessen some of the side effects associated with sulfasalazine, particularly stomach upset. This form of sulfasalazine should not be crushed or chewed. Adequate fluid intake is required to prevent prevent kidney stones. It usually takes between two - three months to notice any improvement in RA symptoms after starting sulfasalazine.

Possible Side Effects

In general, most patients can take sulfasalazine with few side effects. The most common side effects are headache, nausea, and abdominal discomfort, which occurs early in the course of treatment. Serious side effects, such as stomach ulcers, are actually less common with sulfasalazine than with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen.

Abdominal side effects that do occur with sulfasalazine usually improve with time, and are often avoided by slowly increasing from a low starting dose. Sulfasalazine also is available in an enteric-coated (stomach-coated) pill that helps prevent nausea and abdominal discomfort.

Sun sensitivity of the skin can also be a side effect. Those on sulfasalazine should use sunscreen (SPF 15 or higher) when outdoors and avoid prolonged exposure to sunlight. Some people will develop orange colored urine and even orange skin. 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 disease-fighting white blood cells in the body. This often does not cause symptoms, but can be detected by regular blood tests performed by your doctor. Sulfasalazine also increases the risk of reduced blood counts in people born with deficiency of an enzyme called Glucose-6-phosphate dehydrogenase. Most rashes are not serious, but occasionally patients taking sulfasalazine develop a more severe rash and should be evaluated by their doctor to determine if the medication should be discontinued.

Tell Your Rheumatology Provider

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 treatment is generally considered to be safe during pregnancy, but usage should be discussed with your rheumatology provider if you are planning to become pregnant. Based on the recent 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases strongly recommend treatment with sulfasalazine as compatible with breastfeeding. Tell your doctor if you have ever had any unusual or allergic reaction to any other sulfa medicines as well as medicines that are chemically related to sulfa drugs. In men, sulfasalazine may lower sperm count, although this should improve after stopping the medication. Although sulfasalazine may affect sperm count and quality, there are no data suggesting birth defects, and sulfasalazine is conditionally recommended to continue. If conception does not occur, semen analysis should be considered.

Updated February 2022 by the American College of Rheumatology Communications and Marketing Committee.

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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