Sulfasalazine and the 5-aminosalicylates

Patient information: Sulfasalazine and the 5-aminosalicylates

Author
A Christopher Stevens, MD
Section Editor
J Thomas LaMont, MD
Deputy Editor
Shilpa Grover, MD, MPH

Disclosures

OVERVIEW — Sulfasalazine (Azulfidine®) and the 5-aminosalicylate drugs (Asacol®, Pentasa®, Salofalk®, Dipentum®, Colazide®, and Lialda®) are commonly used to treat inflammatory bowel disease. These drugs have anti-inflammatory and immunosuppressive actions, and they are effective for controlling active ulcerative colitis or Crohn’s colitis and for maintaining remission of ulcerative colitis. (See “Patient information: Ulcerative colitis” and “Patient information: Crohn’s disease”.)

Sulfasalazine is also used to treat rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis. (See “Patient information: Rheumatoid arthritis treatment” and “Patient information: Ankylosing spondylitis and spondyloarthritis” and “Patient information: Psoriatic arthritis” and “Patient information: Disease modifying antirheumatic drugs (DMARDs)”.)

In many cases, sulfasalazine or a 5-aminosalicylates 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.

SULFASALAZINE

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.

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; this side effect occurs in 1 to 10 percent of people who take this drug.

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 call 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. In most people, agranulocytosis resolves within one or two weeks of stopping the medication. Testing to monitor the blood count is recommended every two to four weeks initially, then every three to four 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 may be attempted. Desensitization uses 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.

5-AMINOSALICYLATES

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, mesalazine, Asacol®, Pentasa®, Dipentum®, Colazide®, 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.

Side effects

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 and skin rash; 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), inflammation of the pancreas (pancreatitis), and a worsening of inflammation of the colon (colitis). Inflammation of the kidney (nephritis) can also occur, although this can usually be detected with routine blood tests performed during the first few months of therapy.

The 5-ASA drugs can also cause a fall in the number of platelets, a condition called thrombocytopenia; platelets are necessary for blood clotting, and thrombocytopenia can therefore lead to bleeding.

5-aminosalicylates during pregnancy and breastfeeding — The safety of the 5-ASA drugs during pregnancy and breastfeeding is still being studied. Preliminary 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.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

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:

Patient information: Ulcerative colitis
Patient information: Crohn’s disease
Patient information: Rheumatoid arthritis treatment
Patient information: Ankylosing spondylitis and spondyloarthritis
Patient information: Psoriatic arthritis
Patient information: Disease modifying antirheumatic drugs (DMARDs)

Professional Level Information:

Anti-tumor necrosis factor therapy in ulcerative colitis
Azathioprine and 6-mercaptopurine in ulcerative colitis
Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults
Fertility, pregnancy, and nursing in inflammatory bowel disease
Management of ulcerative proctitis, proctosigmoiditis, and left-sided (distal) colitis
Overview of the medical management of mild to moderate Crohn’s disease in adults
Medical management of ulcerative colitis
Sulfasalazine and 5-aminosalicylates in the treatment of ulcerative colitis

The following organizations also provide reliable health information.

National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)

Food and Drug Administration
(www.fda.gov/)

The Crohn’s and Colitis Foundation
(www.ccfa.org)

REFERENCES
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.