Sulfasalazine (Azulfidine)

Sulfasalazine (Azulfidine) is a disease-modifying anti-rheumatic drug (DMARD) indicated for the treatment of adults with RA who have responded inadequately to non-steroidal anti-inflammatory drugs (NSAIDs). A member of a class of drugs called sulfa antibiotics, it was first used in patients with RA about 70 years ago when the disease was thought to result from a bacterial infection.1


How does sulfasalazine work?

Sulfasalazine is made up of two components, aspirin (5-aminosalicyclic acid) and sulfapyridine. It is unclear how these components work together to provide benefit in RA, but we think sulfasalazine may act in a similar way to methotrexate, as an antimetabolite, interfering with the production of key immune system cells. It also appears to inhibit tumor necrosis factor (TNF), which plays an important role in the immune response.2,3


How is sulfasalazine taken?

Sulfasalazine comes in a 500-mg tablet for oral administration and it typically started at a dose of 500 mg per day and 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 gastrointestinal (GI) side effects are problematic, divided doses can be used or a special enteric-coated form (Azulfidine EN-tabs) to protect against GI effects. To help prevent stomach upset, you should take sulfasalazine with food, followed by a full glass of water.1,2


How long does it take for sulfasalazine to achieve full effect?

With sulfasalazine, it typically takes 1 to 3 months before you notice improvements in RA symptoms.1


What should I do if I miss a dose of sulfasalazine?

If you miss a dose of sulfasalazine, take the missed dose as soon as you remember it. However, if it is close to the time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.4


How should I store sulfasalazine?

You should store sulfasalazine in the original container that it came in. Make sure that it is tightly sealed and kept out of reach of children. Keep the container at room temperature and away from moisture (not in your bathroom). Make sure that you discard any sulfasalazine that is outdated. Your pharmacist can tell you how to safely dispose of outdated or unused medication.4


Are there people who should not take sulfasalazine?

People who are allergic to sulfasalazine or its components, salicylates (aspirin, celecoxib) or sulfonamides, should not take sulfasalazine. Tell your doctor if you have ever experienced any allergic or unusual reaction to a sulfa drug. Examples of other sulfa drugs include the antibiotics trimethoprim-sulfamethoxazole (Bactrim, Septra), sulfadiazine, sulfisoxizole (Gantrisin), dapsone, blood pressure and fluid control medications furosemide (Lasix) and thiazide diuretics (hydrochlorothiazide), some diabetes medicines, and some glaucoma medicines, such as acetazolamide (Diamox), dichlorphenamide (Daranide), and methazolamide (Neptazane).

Also, people with intestinal or urinary obstruction should not receive sulfasalazine. In people with a rare blood disorder called porphyria, sulfasalazine may cause an acute attack.5


What evidence do we have that sulfasalazine works in RA?

Clinical studies have shown that sulfasalazine, given as a single drug, is better than placebo and the DMARD hydroxyquinolone and, potentially equivalent to methotrexate and leflunomide, at reducing inflammation and symptoms associated with RA. Additionally, it may be effective in slowing down damage to joints and related structures.

Two meta-analyses of existing studies of sulfasalazine in RA were conducted and found that significant improvements in RA symptoms, including swelling, pain, and inflammation were achieved typically by week 12 of treatment.2

There is some debate concerning how sulfasalazine compares with methotrexate. In one randomized, controlled study conducted in 105 patients with RA, sulfasalazine was found to have equivalent efficacy to methotrexate. However, dosing of methotrexate in this study was low. Additionally, a meta-analysis of studies comparing the two drugs concluded that they had similar efficacy. However, most studies considered in this analysis involved lower doses of methotrexate than are typically used in clinical practice.2

One randomized, controlled study comparing leflunomide (100 mg for 3 days then 20 mg daily) with sulfasalazine and placebo found that both active treatments were superior to placebo and equivalent to one another in improving joint symptoms and slowing disease progression (on x-ray).2

Results from a recent study evaluating sulfasalazine given in combination with methotrexate and hydroxychloroquine (triple therapy) in patients who failed to respond adequately to monotherapy with methotrexate showed that this combination resulted in significant clinical improvement and slowing of radiographic progression comparable to etanercept (Enbrel) plus methotrexate.6

Is regular monitoring recommended while taking sulfasalazine?

Patients who receive sulfasalazine should have complete blood count and liver function tests before starting treatment and every 1 to 2 weeks during the first 3 months of therapy and then every 2 to 4 weeks during the second 3 months of therapy, then every 3 months once a regular dose is achieved.2


What are the side effects of sulfasalazine?

Common side effects associated with sulfasalazine include4:

  • Headache
  • Diarrhea
  • Appetite loss
  • Stomach upset and pain
  • Vomiting


Contact your doctor immediately, if you experience any severe symptoms while taking sulfasalazine. If you experience any of the following symptoms while taking sulfasalazine, stop taking the medication and call your doctor immediately4:

  • 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


Warnings and precautions with sulfasalazine

Sulfasalazine should be used with caution in patients who have liver or kidney damage or disorders of the blood. Signs of serious blood disorders or liver toxicity include fever, pallor, sore throat, purpura or jaundice. Patients who receive sulfasalazine should have complete blood counts and urinalysis regularly.5

Sulfasalazine can result in low sperm count and infertility in men, which is reversible when the drug is discontinued.5

Sulfasalazine should be stopped at the first signs of hypersensitivity (allergic) reactions, including skin rash, mucosal lesions, fever, or enlargement of lymph nodes. In some patients, hypersensitivity reactions to sulfasalazine can be life-threatening.5

Sulfasalazine should be used with caution in patients with severe allergy or bronchial asthma.5


Drug interactions

Sulfasalazine may interact with a number of other medications if they are taken together, requiring adjustment of the dosing of these medications. These include the blood thinner warfarin (Coumadin), cyclosporine, and digoxin. 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), sulfasalazine may increase the risk for low blood sugar.1


Is a generic of sulfasalazine available?


Written by: Jonathan Simmons | Last reviewed: September 2013.
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