Sulfasalazine (Azulfidine)

Pill bottle with pills

Sulfasalazine (Azulfidine) belongs to a class of drugs called sulfa drugs and is used in the treatment of rheumatoid arthritis (RA) and some other autoimmune conditions. It is a combination of salicylate (the main ingredient in aspirin) and a sulfa antibiotic. Sulfasalazine is also known as a disease modifying antirheumatic drug (DMARD), because it not only decreases the pain and swelling of inflammatory arthritis, but may also prevent damage to joints.  In addition, it may reduce the risk of long term loss of function.

Sulfasalazine is a DMARD. DMARDs work to decrease pain and inflammation, reduce/prevent joint damage, and preserve joint mobility. So, Sulfasalazine treats swelling, pain, and stiffness in inflammatory arthritis. However, it is not entirely clear how this medication works for RA.

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 crystalluria and stone formation.

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 nausea and abdominal discomfort, which often occurs in up to a third of patients 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 (Advil) or naproxen (Aleve).

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.

Only about 10% of patients on this medicine will get a skin rash or headache. Even less commonly, patients taking this medication for RA will get mouth sores, itching, liver function abnormalities, or lung problems (rare).

Burning or skin damage from sunlight can also be a problem. 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, leading to a higher risk for infections. 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.

Potential Severe Reaction: 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 Doctor

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 drugs – sulfonylureas 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 physician if you are planning to become pregnant. Additionally, sulfasalazine may reduce levels of folate (a vitamin) in the body, and your doctor may recommend taking a folic acid supplement while on the medication, which is especially important if pregnancy is being considered. This medication should not be taken by mothers who are breastfeeding, as it increases the risk for a type of jaundice in the newborn (kernicterus) that can cause brain problems in infants younger than two years old. In men, sulfasalazine may lower sperm count, although this should improve after stopping the medication.

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. Your doctor will then determine whether you should take sulfasalazine. Sulfa drugs and those related to them include:

  • Some antibiotics (often used to treat urinary or upper respiratory infections): trimethoprim-sulfamethoxazole (Bactrim, Septra) sulfadiazine, sulfisoxizole (Gantrisin), and dapsone
  • Fluid and blood pressure pills such as furosemide (Lasix) and thiazide diuretics (hydrochlorothiazide or HCTZ)
  • Some diabetes medications
  • Some glaucoma medications such as acetazolamide (Diamox), dichlorphenamide (Daranide), and methazolamide (Neptazane)
  • Salicylates such as aspirin and the Cox-2 inhibitor celecoxib (Celebrex)

Complete blood counts, liver and kidney functions should be checked at baseline, every 2 - 4 weeks for first 3 months, every 8 weeks during next 3 months, followed by every 12 weeks thereafter to monitor for any side effects.

Updated June 2017 by Deepak Gupta, 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.