Sulfasalazine alternatives: What can I take instead of sulfasalazine?

Compare sulfasalazine alternatives | Actemra | Enbrel | Humira | Methotrexate | Remicade | Natural alternatives

If you have rheumatoid arthritis or ulcerative colitis, you may have heard of a drug called sulfasalazine. Sulfasalazine is the ingredient and generic version of the brand-name prescription drug, Azulfidine, which is made by Pfizer. Sulfasalazine is used for the following conditions:

• To treat mild to moderate ulcerative colitis (UC), which is a type of inflammatory bowel disease (IBD)
• To treat severe UC, in combination with other medication(s)
• To lengthen the time between UC attacks (flare-ups)

Azulfidine EN-tabs are another formulation that contains delayed-release, enteric-coated sulfasalazine. Sulfasalazine delayed-release tablets can treat the conditions listed above. In addition, sulfasalazine delayed-release tablets can treat patients with rheumatoid arthritis (RA) who have not responded to or cannot tolerate other medications. This drug can also treat children with polyarticular-course1 juvenile RA who have not responded to other medications.

Sulfasalazine is part of a drug class called disease-modifying anti-rheumatic drugs (DMARDs), more specifically, it is an aminosalicylate. It works to treat these autoimmune conditions by decreasing inflammation in the body. It is approved by the U.S. Food and Drug Administration (FDA).

In some cases, patients may be looking for an alternative treatment option to sulfasalazine. Some people may not have the desired effect and want to try a different medication to see if it works better. Others may have side effects that persist or are bothersome. Common side effects of sulfasalazine include:

• Abnormal liver function tests
• Appetite loss
• Blood in the urine
• Crystals in the urine which can cause stones or kidney problems
• Cyanosis (blue skin due to poor circulation)
• Dizziness
• Fever 
• Headache
• Hemolytic anemia (a condition where red blood cells are destroyed faster than they are made)
• Leukopenia (low white blood cell count, which can interfere with the body’s ability to fight infection and increase the risk of infection)
• Low sperm count
• Sensitivity to the sun
• Skin rash/itching/hives
• Stomach problems like pain, nausea, vomiting, and indigestion
• Swelling and sores in the mouth

Or, a serious side effect could occur, such as seizures, low blood sugar, infections, problems with the lungs, liver, kidneys, or pancreas, or severe or life-threatening allergic reactions or skin reactions. 

Some people cannot take sulfasalazine at all. According to the prescribing information, sulfasalazine is not approved for use in:

• Patients with an intestinal or urinary blockage
• Patients with a condition called porphyria 
• Patients who are allergic to sulfasalazine, mesalamine, sulfa drugs, or salicylates

If you are looking for a different medication, there are several alternatives to sulfasalazine that you can discuss with your healthcare provider. 

What can I take in place of sulfasalazine?

There are other options available to treat UC or RA symptoms that do not improve with sulfasalazine, or when sulfasalazine cannot be tolerated. The table below compares sulfasalazine (in bold), with common alternatives. All of the drugs listed are prescription medications that are approved by the FDA. 

Other alternatives to sulfasalazine

• Apriso (mesalamine) oral: for UC
• Asacol HD (mesalamine) oral: for UC
• Delzicol (mesalamine) oral: for UC
• Pentasa (mesalamine) oral: for UC

Top 5 sulfasalazine alternatives

1. Actemra

Actemra is an injection that contains the ingredient tocilizumab, which can be given intravenously (into a vein over a one-hour period) or subcutaneously (as an injection under the skin). 

Actemra is in a drug class called interleukin-6 (IL-6) receptor antagonists. It is also known as a biologic. Actemra can be used for:

• Adults with moderate to severe RA who have not responded to other medication(s)
• Adults with giant cell arteritis
• Adults with systemic sclerosis-associated interstitial lung disease
• Patients 2 years and older with polyarticular juvenile idiopathic arthritis or systemic juvenile idiopathic arthritis
• Adults and children 2 years and older with cytokine release syndrome

The most common side effects of Actemra are headache, injection site reactions, high blood pressure, upper respiratory tract infections, common cold, and increased liver function tests. 

Actemra has a black box warning, which is the most serious warning required by the FDA. The warning states that Actemra can cause serious infections that can lead to hospitalization or death. These infections may include tuberculosis (TB), or other bacterial, viral, or fungal infections. If a serious infection occurs, Actemra should be stopped until the infection is controlled. Before starting Actemra, patients should be tested for TB, and treated if the test is positive. During treatment, patients should be monitored for TB. 

2. Enbrel

Enbrel is an injection. It contains the ingredient etanercept, which is given subcutaneously every week. 

Enbrel is in a drug class called tumor necrosis factor (TNF) blockers. It is also a biologic.
Enbrel can be used for:

• RA
• Psoriatic arthritis
• Ankylosing spondylitis
• Plaque psoriasis (adults and children 4 years and older)
• Polyarticular juvenile idiopathic arthritis (in patients 2 years and older)

Common side effects of Enbrel include injection site reactions and infections. 

Enbrel has the same black box warning as Actemra. Additionally, the black box warning states that lymphoma and other malignancies (cancers), some of which have caused death, have occurred in children and adolescents who have taken TNF blockers. 

3. Humira

Humira is an injection and contains the ingredient adalimumab, which is given subcutaneously every week or every two weeks. 

Like Enbrel, Humira is in a drug class called tumor necrosis factor (TNF) blockers. It is also a biologic. Humira can be used for:

• Moderate to severe RA in adults
• Juvenile idiopathic arthritis in patients 2 years and older
• Psoriatic arthritis in adults
• Ankylosing spondylitis in adults
• Moderate to severe Crohn’s disease in adults and children 6 years and older
• Moderate to severe ulcerative colitis in adults and children 5 years and older
• Plaque psoriasis in adults
• Moderate to severe hidradenitis suppurativa in patients 12 years and older
• Uveitis in adults and children 2 years and older

Common side effects of Humira include injection site reactions, headache, rash, upper respiratory infections, and sinus infections. 

Humira has the same black box warning as Enbrel. Additionally, the black box warning states that a rare type of T-cell lymphoma, called hepatosplenic T-cell lymphoma, has occurred in adolescents and young adults with inflammatory bowel disease who were treated with TNF blockers. 

4. Methotrexate

Methotrexate is available in both oral and injection forms. 

Methotrexate is in a drug class called dihydrofolate reductase inhibitors. Oral methotrexate can be used for:

• Adults and children with acute lymphoblastic leukemia
• Adults with mycosis fungoides
• Adults with non-Hodgkin lymphoma
• Adults with RA
• Adults with severe psoriasis
• Pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA)

Injectable methotrexate can be used for RA, pJIA, psoriasis, and several times of cancers.

The most common methotrexate side effects are nausea, stomach problems, low white blood cells, and ulcers in the mouth. Folic acid supplementation should be given to lower the risk of side effects from methotrexate.

Methotrexate has a black box warning. This drug can harm an unborn baby, and may cause death. Methotrexate should not be used for non-neoplastic (non-cancer) diseases in pregnant women. Women of childbearing age should be educated about the risk to an unborn baby and should speak to their healthcare provider about using effective contraception. People who are allergic to methotrexate should not take this drug. Methotrexate can cause serious reactions, including death. Patients who take this drug should be closely monitored for bone marrow, stomach, lungs, kidneys, skin, and liver problems. 

5. Remicade

Remicade is an injection that contains the ingredient infliximab, which is given intravenously every six to eight weeks, depending on the indication. 

Remicade is a TNF blocker and a biologic. It can be used for:

• Crohn’s disease in adults and children 6 years and older
• Ulcerative colitis in adults and children 6 years and older
• RA in adults (in combination with methotrexate)
• Ankylosing spondylitis in adults
• Psoriatic arthritis in adults
• Plaque psoriasis in adults

The most common side effects of Remicade are headache, infusion-related reactions, upper respiratory tract infections, sinus infections, sore throat, and stomach pain. 

Remicade has the same black box warning as Humira. 

Related: Remicade vs. Humira

Natural alternatives to sulfasalazine

If you are experiencing RA, you may be wondering if there is a natural alternative to sulfasalazine. While supplements do not replace prescription medications, there are some vitamins and supplements that may help improve symptoms. Before taking any vitamin or supplement, though, consult your healthcare provider. 

1. Folic acid: Many people who have RA take a drug called methotrexate, which can deplete folic acid levels. When taking methotrexate, supplementation with folic acid will be necessary. Folic acid will also help reduce some of the side effects of methotrexate.
2. Calcium and vitamin D: It’s important to get enough calcium and vitamin D if you have RA and you also have bone loss. Steroids, such as prednisone, which are sometimes prescribed for RA, can also cause bone loss, making it important to supplement with calcium and vitamin D. Your healthcare provider can look at the results of your blood tests and recommend an appropriate dosage to take.
3. Omega-3 fatty acids (fish oil): These supplements may help improve RA symptoms, such as joint pain, morning stiffness, and swollen joints. 
4. CBD: While it may be tempting to hop on the CBD bandwagon, consult your healthcare professional before trying this natural product. Although there are no clear guidelines on CBD and arthritis, medical experts with the Arthritis Foundation remind patients that there is little data on CBD use in patients with arthritis. There are also potential drug interactions to be aware of. CBD, like other supplements, should never be used in place of prescription medicine. Patients who want to try CBD should start with a low dose, increasing slowly if needed. Patients should purchase CBD from a reputable business that has each batch evaluated for purity, safety, and potency by an independent lab, and has a certificate of analysis.

Again, these vitamins or supplements are not a substitute for medication, but rather a potential complement to the medication. Talk to your healthcare professional about various natural methods you can try, in combination with your medications. Always check with your healthcare provider for medical advice before trying an herbal supplement, as some may have drug interactions or dangerous adverse effects. 

How to switch to a sulfasalazine alternative

If you are interested in switching to a sulfasalazine alternative, you can:

• Contact your insurance provider if the price is a concern. Ask which sulfasalazine alternatives are covered in your formulary, and what the copay would be for each medication. Be sure to ask if your deductible has been met, or if you are still paying towards your deductible. 
• Reach out to your healthcare provider. You may be asked to make an appointment to talk about your medication regimen. You can review your medical conditions and history, and discuss alternative medications—as well as potential side effects and drug interactions—with your healthcare provider. If your provider decides to prescribe a sulfasalazine alternative, they can send the prescription to your pharmacy. Tell your pharmacist that you are switching from sulfasalazine to the new medication, so they can update your file.
• Search SingleCare for coupons. SingleCare customers save up to 80% on prescription prices, and the coupons can be applied to refills, too.