Patient information: Sulfasalazine and the 5-aminosalicylates (Beyond the Basics)
- Adam S Cheifetz, MD
Adam S Cheifetz, MD
- Associate Professor of Medicine
- Harvard Medical School
- Garret J Cullen, MD
Garret J Cullen, MD
- Consultant Gastroenterologist
- St. Vincent's University Hospital, Dublin
Sulfasalazine (Azulfidine) and the 5-aminosalicylate drugs (Asacol, Delzicol, Asacol HD, Pentasa, Salofalk, Dipentum, Colazal, Apriso and Lialda) are commonly used to treat inflammatory bowel disease. These drugs have anti-inflammatory actions, and they are effective for inducing and maintaining remission in mild to moderate ulcerative colitis. Their efficacy in Crohn’s disease is more controversial. Sulfasalazine appears to be effective in controlling active Crohn’s colitis. (See "Patient information: Ulcerative colitis (Beyond the Basics)" and "Patient information: Crohn disease (Beyond the Basics)".)
Sulfasalazine is also used to treat rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis. (See "Patient information: Rheumatoid arthritis treatment (Beyond the Basics)" and "Patient information: Ankylosing spondylitis and other spondyloarthritis (Beyond the Basics)" and "Patient information: Psoriatic arthritis (Beyond the Basics)" and "Patient information: Disease-modifying antirheumatic drugs (DMARDs) (Beyond the Basics)".)
In many cases, sulfasalazine or a 5-aminosalicylate must be taken for a long period of time. These medications can have side effects ranging from mild to serious. Many of the mild side effects can be avoided by using lower doses of these drugs; the serious side effects are uncommon or rare, and usually resolve when the medication is stopped. In most cases, the potential benefits of these drugs outweigh the potential risks. Nonetheless, it is important to be aware of the possible side effects before starting treatment.
How it works — Sulfasalazine acts locally in the colon to decrease inflammation. It also works throughout the body by inhibiting the formation of a chemical known as prostaglandins. Prostaglandins have several important functions in the body, one of which is control of pain and inflammation.
Sulfasalazine is a yellow/orange color; patients who take it may notice that their urine, tears, and sweat develop an orange tinge, which can stain clothing and contact lenses. Patients should drink plenty of fluids while on therapy and avoid taking the drug on an empty stomach or with antacids. Sulfasalazine can affect folate absorption, so patients should take folic acid (1 mg/day) while taking the medication.
Side effects — The major side effects of sulfasalazine can be classified according to how frequently the side effect occurs: commonly, uncommonly, and rarely.
Common side effects — The most common side effects of sulfasalazine are headache, nausea, fever, rash, and reversible infertility in men.
Headache is one of the most common complaints, affecting up to one-third of people. Headaches are more likely with higher doses of the drug, and are less likely to occur if the dose is gradually increased. Loss of appetite, nausea, sensitivity to sunlight, and nervousness are also common when starting therapy. Sperm count may be reduced in men who take sulfasalazine, although this is reversible once the drug is stopped.
Uncommon side effect — Inflammation of the pancreas (pancreatitis) is an uncommon side effect of sulfasalazine.
Rare side effects — Rare and potentially serious side effects of sulfasalazine (affecting less than 1 percent of people who take this drug) include inflammation of the liver (hepatitis), inflammation of the lung (pneumonitis), a serious skin reaction called Stevens-Johnson syndrome, and destruction of red blood cells (hemolysis).
Rarely, there is a decrease in the number of infection fighting white blood cells. In some cases, the bone marrow completely stops producing a specific type of white blood cells, a condition called agranulocytosis. Agranulocytosis usually occurs within two months of starting sulfasalazine and is usually accompanied by a fever and rash. In most people, agranulocytosis resolves within one or two weeks of stopping the medication. Testing to monitor the blood count is recommended in all patients on sulfasalazine. This should be performed every one to two weeks for the first six weeks, monthly for three months, and then every three months.
Sulfasalazine and sulfa allergies — People who are allergic to sulfa drugs may have a cross reaction to sulfasalazine and should therefore not take it. If sulfasalazine produces mild allergic symptoms but very effectively controls symptoms, desensitization, a method to reduce or eliminate the allergic reaction, may be attempted. Desensitization uses a very small dose of sulfasalazine initially, and gradually increases the dose over time. This strategy is not commonly done for people with inflammatory bowel disease since other treatments are available.
Sulfasalazine during pregnancy and breastfeeding — Women who wish to become pregnant can continue taking sulfasalazine during pregnancy and while breastfeeding. Sulfasalazine does not increase the risk of any complications of pregnancy or the risk of birth defects. Pregnant patients taking sulfasalazine should increase their folate supplementation to 2 mg/ day.
How they work — Sulfasalazine is a molecule that has two components: 5-aminosalicylate (5-ASA) and sulfapyridine. The sulfapyridine is responsible for many of the side effects of sulfasalazine, while the 5-ASA is responsible for many of its beneficial effects in patients with inflammatory bowel disease. This discovery provided a rationale for the development of a drug that contains only the 5-ASA component. Unfortunately, the sulfapyridine component is necessary for the beneficial effects of sulfasalazine in patients with rheumatoid arthritis; thus the 5-ASA drugs are not suitable for those patients.
Several formulations of the 5-ASA drugs are available (eg, Asacol, Delzicol, Asacol HD, Pentasa, Dipentum, Colazal, Apriso, and Lialda). These differ in the specific formulation of 5-ASA, how many times per day they are taken, and the way the pills dissolve in particular parts of the bowel.
Overall, the 5-ASA drugs have fewer side effects than sulfasalazine. However, about 20 percent of people who have side effects while taking sulfasalazine will have similar side effects while taking 5-ASA drugs.
Common side effects — The most common side effects of the 5-ASA drugs (occurring in more than 10 percent of people) include headache and malaise (a vague feeling of illness), cramps and gas. Watery diarrhea is fairly common with one of the 5-ASA formulations (Dipentum), occurring in about 15 percent of people.
Uncommon side effects — Uncommon side effects include hair loss, skin rash, and a worsening of inflammation of the colon (colitis); these occur in 1 to 10 percent of people.
Rare side effects — Rare side effects affect less than 1 percent of people, but are potentially serious. They include inflammation of the lung (pneumonitis), inflammation of the tissue surrounding the heart (pericarditis), and inflammation of the pancreas (pancreatitis). Inflammation of the kidney (interstitial nephritis) can also occur, although this can usually be detected with routine blood tests performed at six weeks and at six months after starting a 5-ASA medication, and yearly thereafter.
5-aminosalicylates during pregnancy and breastfeeding — 5-ASA drugs appear to be safe during pregnancy and breastfeeding. Studies suggest that they are safe when taken during pregnancy and that women should continue taking these drugs during pregnancy. However, women who take 5-ASA medications should speak to their clinician before trying to conceive. The US Food and Drug Administration (FDA) has changed Asacol and Asacol HD from pregnancy category B to category C because of concerns over the presence of a chemical called dibutyl phthalate (DBP) in the coating of these drugs. Delzicol, the newest 5-ASA, was formulated without DBP in the coating and FDA approved. Asacol will no longer be manufactured. Because the remaining 5-ASA drugs remain pregnancy category B, physicians may consider switching pregnant patients taking Asacol or Asacol HD to an alternative 5-ASA.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient Level Information:
Patient information: Ulcerative colitis (Beyond the Basics)
Patient information: Crohn disease (Beyond the Basics)
Patient information: Rheumatoid arthritis treatment (Beyond the Basics)
Patient information: Ankylosing spondylitis and other spondyloarthritis (Beyond the Basics)
Patient information: Psoriatic arthritis (Beyond the Basics)
Patient information: Disease-modifying antirheumatic drugs (DMARDs) (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Anti-tumor necrosis factor therapy in ulcerative colitis
Azathioprine and 6-mercaptopurine in inflammatory bowel disease
Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults
Fertility, pregnancy, and nursing in inflammatory bowel disease
Management of mild to moderate ulcerative colitis
Overview of the medical management of mild to moderate Crohn disease in adults
Management of severe ulcerative colitis
Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease
The following organizations also provide reliable health information.
- National Library of Medicine
- Food and Drug Administration
- The Crohn's and Colitis Foundation
- Sutherland L, Roth D, Beck P, et al. Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis. Cochrane Database Syst Rev 2000; :CD000543.
- Hanauer SB, Sandborn WJ, Kornbluth A, et al. Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial. Am J Gastroenterol 2005; 100:2478.
- Bell CM, Habal FM. Safety of topical 5-aminosalicylic acid in pregnancy. Am J Gastroenterol 1997; 92:2201.
- Diav-Citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology 1998; 114:23.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.