What to Know About Sulfasalazine

A Disease-Modifying Anti-Rheumatic Drug for Inflammatory Conditions

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Sulfasalazine is a disease-modifying anti-rheumatic drug (DMARD). It can be used alone or with other treatments. Sulfasalazine works by changing the way a disease affects the body.

It can reduce joint inflammation, pain, and stiffness from a variety of inflammatory arthritis conditions like rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). It is also used to treat ulcerative colitis (UC), a chronic, inflammatory bowel disease that causes inflammation of the digestive tract.

Sulfasalazine is available under the brand name Azulfidine. It is also available as a generic drug that costs less than the brand-name version. Learn about the uses of sulfasalazine, what to know before starting it, how to take it, side effects, and more.


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How sulfasalazine works isn’t well understood, but researchers think it interrupts processes in the body that generally cause inflammation. 

Sulfasalazine is often recommended for treating JIA. Sometimes called juvenile rheumatoid arthritis, JIA is the most common type of arthritis affecting children and teens. In one randomized, placebo-controlled study reported in 2013, researchers found sulfasalazine was a safe and effective treatment for JIA, including JIA that included enthesitis. 


Enthesitis means there is inflammation of the entheses, the places where ligaments or tendons insert into the bone.

In RA, a type of inflammatory arthritis mainly affecting the joints, sulfasalazine can help people who have not responded well to other treatments. It can help to reduce pain and swelling in the joints by affecting the processes that cause inflammation. It is especially helpful when used with other therapies (combination therapy) like methotrexate.

For UC, sulfasalazine can treat stomach and gut inflammation. It might also reduce the number of UC flares you experience. Research on UC has found sulfasalazine to be effective in cases where other UC therapies have not helped.

Sulfasalazine can also help with treating mild to moderate pain associated with UC. It is often used with other drugs for treating UC.

Off-Label Uses

Off-label uses for sulfasalazine include treating ankylosing spondylitis, Crohn’s disease, psoriasis, and psoriatic arthritis.

Off-label use means a drug or other therapy is being used in a manner not indicated on the Food and Drug Administration (FDA) labeling for the treatment. Before the FDA approves a drug to be used off-label, the drug manufacturer must prove the drug is safe and effective for the intended use.

Ankylosing spondylitis (AS): The American College of Rheumatology has recommended sulfasalazine for people with active AS for whom nonsteroidal anti-inflammatory drugs (NSAIDs) have not helped or have had contraindications to anti-TNF inhibitor drugs (a type of biologic drug).

Crohn’s disease: According to the American College of Gastroenterology's clinical guidelines for the management of Crohn’s disease in adults, sulfasalazine is a safe and effective treatment for mild and moderately active Crohn’s disease.

Psoriasis and psoriatic arthritis (PsA): According to the National Psoriasis Foundation, sulfasalazine can be used off-label for treating both psoriasis and PsA.

Before Taking

Sulfasalazine is a first-line conventional DMARD therapy often used to reduce inflammation and pain from many different inflammatory conditions. First-line therapy means it is given as the first therapy for a disease or illness.

Before deciding to prescribe sulfasalazine to treat your inflammatory condition, your healthcare provider will explain all the risks and benefits connected to the medicine. The decision to start treatment is one you and your practitioner will make together.

To help make that decision, your healthcare provider will consider other conditions you have, current treatments for those conditions, allergies, and other factors like your age and general health. 

Precautions and Contraindications

Before starting sulfasalazine, your healthcare provider needs to know if you are allergic to sulfa drugs or salicylates. Sulfa drugs are derived from sulfanilamide, a sulfur-containing chemical. Salicylate is found in aspirin and some foods.

Sulfasalazine can interact with other medications, herbal supplements, and vitamins you may be taking. A drug interaction might change the way a medicine works. Interactions can cause harm or prevent a drug from working well.

The best way to avoid interactions is to make sure your practitioner knows about all the medicines, vitamins, and herbal supplements you take.

The research on sulfasalazine finds the drug does not increase pregnancy complications or the risk for birth defects. Even so, let your healthcare provider know if you are pregnant, plan to become pregnant, or are breastfeeding before starting sulfasalazine, so your practitioner can make treatment decisions specific to your health situation.

Some people shouldn’t take sulfasalazine. This includes people who have blockage of their bladder or in their intestines and people with porphyria, a genetic enzyme condition that causes skin and nervous system symptoms.

The safety and effectiveness of sulfasalazine have not been established in children ages 2 and under. It may be prescribed for children as young as 6 years of age for managing JIA and UC at a healthcare provider’s discretion.

Other DMARDs

DMARDs are drugs that act upon the immune system to slow down the progression of inflammatory autoimmune diseases—conditions that cause the body to attack its healthy tissues. There are many commonly used DMARDs, and most can be used in combination with sulfasalazine.

Plaquenil (hydroxychloroquine) is used for mild RA, lupus, and other autoimmune diseases. It is not considered as powerful as other DMARDs, but it might cause fewer side effects. Plaquenil can adversely affect the eyes in rare cases, so people taking this medication can see an ophthalmologist within the first year of therapy, then have yearly follow-up appointments.

Methotrexate is the most commonly used DMARD. It has been shown to work better than any other single treatment for many autoimmune diseases. Like other DMARDs, it can cause side effects, including rash, upset stomach, liver toxicity, and birth defects. Your healthcare provider will want you to have regular blood work while on methotrexate.

Arava (leflunomide) is believed to work as well as methotrexate, and it works better in combination with methotrexate. Side effects are similar to methotrexate.

Biologic DMARDs such as Orencia (abatacept), Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab) are newer drugs for treating autoimmune diseases like RA. They are given by injection or intravenous infusion. They neutralize one or more of the immune system signals that trigger inflammation and joint damage.

Biologics can increase your risk of all types of infections. Reach out to your healthcare provider if you experience signs of an infection, including fever, chills and sweats, cough, sore throat, shortness of breath, nasal congestion, stiff neck, and burning or pain with urination.


Sulfasalazine is available in immediate-release and extended-release 500 milligram (mg) oral tablets.

The listed dosages are the manufacturer's recommendations. Your dosage, formulation, and how often you take the drug will depend on the condition being treated, how severe the condition is, other medical conditions, your age, and how you respond to the first dose.

For treating RA and other types of inflammatory arthritis, sulfasalazine is usually given to adults at 500 mg to 1,000 mg per day, up to twice daily. The maximum daily dose is capped at 3,000 mg per day. For children, ages 6 and older, the dosage is based on body weight and capped at 2,000 mg per day. It is rarely given to children under 6.

For treating UC, the dosage for adults is 500 mg to 1,000 mg every six to eight hours, capping at 4,000 mg per day. For children ages 6 and older, the dosage is based on body weight.

How to Take and Store 

Sulfasalazine is a long-term treatment. It is usually safe to take but might come with risks if you don’t take it as prescribed.

For example, if you stop taking the drug or don’t take it all, you are more likely to experience flare-ups of the condition it was prescribed to treat. It is never a good idea to stop taking a medication before talking to your healthcare provider.

If you are missing doses or not taking the medication as scheduled, sulfasalazine might not work as well, or it might stop working. For sulfasalazine to work correctly, it needs to be in your body at all times. If you miss a dose, take it as soon as you remember. If it is time to take your next dose, don’t double up doses; just take the next dose.

If you take too much, there might be a buildup to high or dangerous levels of the drug in your body, which might lead to an overdose. Taking too much might increase your risk of side effects, especially more serious ones.

Signs you have taken too much sulfasalazine include nausea and vomiting, stomach pain, drowsiness, and seizures. Overdoses with this drug are rare.

If you think you have taken too much, call your healthcare provider or contact the American Association of Poison Control Centers at 800-222-1222. If you have severe symptoms, call 911 or head to a nearby emergency room.

To avoid stomach upset, the best time to take sulfasalazine is after a meal or with a snack. It should be taken with a full glass (8 ounces) of water to prevent kidney stones. Make sure you take the drug at the same time each day, and try not to let more than eight hours pass between doses.

The tablets should be taken whole. Do not crush, break, split, or chew the tablets.

Drink extra fluids with sulfasalazine because the drug will cause you to need to urinate more. Drinking more water will also help reduce your risk of kidney problems.

If you see a tablet in your stool, you should let your healthcare provider know. This might be a sign your body is not absorbing the medicine.

You will know sulfasalazine is working because you will have reduced symptoms from your inflammatory condition. With inflammatory arthritis, you will have less joint pain. For UC, you will have less stomach pain and less frequent flare-ups.

Sulfasalazine should be kept in the container it came in, tightly closed, and out of the reach of children and pets. Store the drug at room temperature and away from excess heat and moisture.

Additional Considerations

Keep these additional considerations in mind while treating with sulfasalazine:

  • Vaccinations: It is usually OK for people who take sulfasalazine to have vaccinations, but you should always check with your treating practitioner to make sure a vaccine is safe. Your healthcare provider will likely recommend you get a pneumococcal vaccine every five years and a yearly flu shot
  • Follow-ups: It is important to check in with your practitioner regularly while on sulfasalazine. This way, your healthcare provider can check if the medication is working correctly. Additionally, they will want you to have blood, liver, and kidney tests to check for unwanted drug effects. 
  • Blood work: Sulfasalazine can decrease some of your blood cell counts and increase your risk of infection. Early on, your practitioner will want to check your blood work more frequently. After that, blood work is less frequent.
  • Liver tests: Sulfasalazine increases the risk of liver injury. Your healthcare provider will want you to come in regularly for liver function testing, blood tests that provide information about the condition of your liver. 
  • Kidney function: Researchers do not know why sulfasalazine causes adverse kidney effects in some people. Your healthcare provider will want you to come in regularly for kidney function tests so that any problems with your kidneys can be addressed before they become serious. 

Kidney function tests are blood and urine tests that can help to identify problems with the kidneys. If the kidneys are not working well, they will not be able to rid the body of the drug, which will increase side effects from the drug.

Side Effects

Sulfasalazine may cause unwanted side effects. Some are common and others are severe and might affect your ability to take the drug.

Common Side Effects

Most side effects usually happen in the first three months of treatment with sulfasalazine and will resolve once the dose is reduced. If you are experiencing side effects, your practitioner may reduce the dose by 50%. Your healthcare provider might be able to increase your dose if your reaction to the drug improves and the drug is helping.

The most common side effects of sulfasalazine are:

  • Headache
  • Dizziness
  • Rash
  • Diarrhea
  • Orange urine color
  • Reduced sperm count

According to the Cleveland Clinic, common side effects of sulfasalazine usually do not require medical treatment. However, if side effects persist or are bothersome, you should let your healthcare provider know.

Severe Side Effects

Severe side effects should be reported to your healthcare provider as soon as possible. Severe side effects of sulfasalazine might include:

  • Allergic reaction: Symptoms might include skin rash, itching, hives, or swelling of the face, lips, tongue, or throat.
  • Painful, difficult, or reduced urination
  • Skin symptoms: Redness, blistering, or peeling of the skin or inside of the mouth
  • Severe abdominal pain
  • Unusual bleeding or bruising
  • Extreme weakness or fatigue
  • Yellowing of the skin or eyes

Warnings and Interactions

Sulfasalazine comes with warnings. These include a sun sensitivity warning, an increased risk of infection, and a sulfa allergy warning.

Sun Sensitivity

Sulfasalazine can make you more sensitive to sunlight. Plan to avoid unnecessary and prolonged exposure to sunlight and wear sunscreen, sunglasses, and protective clothing when out in the sun for long periods. Do not use sunlamps or tanning beds.

Infection Risk

Sulfasalazine can increase your risk of infection. This is because the drug works by lowering your body’s immune defenses. Let your healthcare provider know right away if you think you might have an infection.

Signs of infection might include:

  • Sore throat
  • Fever
  • Chills
  • Shortness of breath
  • Stiff neck
  • Nasal congestion
  • Urinary symptoms: frequency or burning or pain with urination
  • Nausea and vomiting
  • Abdominal pain
  • Redness, soreness, or swelling of any area of the body

Because sulfasalazine increases your infection risk, you will want to find ways to reduce your risk.

Some ways to reduce your risk of infection are:

  • Avoid contact with people who are sick. If you have to visit someone who is sick, wear a mask and wash your hands frequently.
  • Handwashing is always important. Wash your hands regularly and carry a small bottle of hand sanitizer with you.
  • Stop smoking if you smoke.
  • Brush your teeth regularly. Be careful when using a toothbrush, dental floss, or toothpicks. Make sure you are seeing a dentist regularly.
  • Store and prepare food properly.
  • Keep your home clean and hygienic, especially the kitchen and bathroom.


Sulfasalazine can cause a severe allergic reaction, especially in people allergic to sulfa drugs. A 2019 report in the journal Pharmacy finds up to 8% of people have had an allergic reaction to a sulfa drug.

Symptoms of an allergy to sulfasalazine might include breathing trouble, tongue or throat swelling, and hives. If you develop these signs, call 911 or go to the nearest emergency room.


Sulfasalazine might interact with other medicines. Drugs known to interact with sulfasalazine include folic acid and a drug used to treat heart failure called digoxin.

Folic acid, also called vitamin B9, is less absorbed by the body when taken with sulfasalazine. Your healthcare provider might recommend you take a high-dose folic acid supplement with sulfasalazine.

When taking sulfasalazine with digoxin, the body will absorb less digoxin. Your practitioner might monitor your digoxin dosage and increase the amount if needed.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Lana Barhum
Lana Barhum has been a freelance medical writer since 2009. She shares advice on living well with chronic disease.