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Ulcerative colitis - Medications

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of ulcerative colitis.

Alternative Names

Inflammatory bowel disease - ulcerative colitis; Colitis - ulcerative

Medications:

Aminosalicylates

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn‚ ' s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine or who are allergic to sulfa drugs have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are taken as pills several times a day. In 2007, the Food and Drug Administration approved LIALDA, the first once-daily mesalamine pill for patients with ulcerative colitis. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

  • Abdominal pain and cramps (mesalamine, balsalazide)
  • Diarrhea (mesalamine, olsalazine)
  • Gas (mesalamine)
  • Nausea (mesalamine)
  • Hair loss (mesalamine)
  • Headache (mesalamine, balsalazide)
  • Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children and women who are pregnant or nursing.

Corticosteroids

Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs. They are used only for active ulcerative colitis. Steroids are frequently combined with other drugs to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time. Because the oral form has serious long-term effects, they are not useful for maintenance therapy. Patients who have a poor response to steroids are also less likely to do well with repeat therapy.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef and Cortisol) are the most common oral corticosteroids. Newer steroids, such as budesonide (Entocort), are given via enema and affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. They are only helpful for milder ulcerative colitis involving the rectum and sigmoid colon.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Oral steroids can have distressing and sometimes serious long-term side effects, including:

  • Susceptibility to infection
  • Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
  • Acne
  • Excess hair growth
  • High blood pressure (hypertension)
  • Weakened bones (osteoporosis)
  • Cataracts and glaucoma
  • Diabetes
  • Muscle wasting
  • Menstrual irregularities
  • Upper gastrointestinal ulcers
  • Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

Immunosuppressive Drugs

Immunosuppressant drugs are now being used for long-term therapy, especially for very active inflammatory bowel disease that does not respond to standard treatments. Such drugs suppress or restrain actions of the immune system and therefore its inflammatory response, which causes ulcerative colitis. Immunosuppressants can prevent relapse, even when used alone, and in some studies have proved to help maintain remissions in ulcerative colitis for up to 2 years.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). Cyclosporine A is also given intravenously to patients with severe ulcerative colitis. These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. Methotrexate (MTX, Rheumatrex) is another fast-acting type of injectable immunosuppressant that is effective for Crohn‚ ' s disease. However, methotrexate does not appear to be helpful for ulcerative colitis. (Antibiotics, which are used to treat Crohn's disease, are also not helpful for ulcerative colitis.)

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly. Immunosuppressants are usually not recommended for women who are pregnant or breast-feeding.

Biologic Drugs (Infliximab)

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body‚ ' s inflammatory response. One such drug, infliximab (Remicade), was approved in 2005 for treatment of moderate-to-severe ulcerative colitis in patients who have not responded to other drugs, such as corticosteroids. In 2006, infliximab was approved to help maintain as well as induce remission. Doctors do not recommend infliximab as a first-line drug for ulcerative colitis.

Infliximab targets an inflammatory immune factor known as tumor necrosis factor (TNF). Studies indicate that infliximab may reduce ulcerative colitis symptoms and help patients achieve remission. Infliximab may also help heal ulcers and inflammation of the colon‚ ' s inner lining (mucosa). Some patients who take infliximab may be able to avoid surgical removal of the colon.

Infliximab is given as a 2-hour intravenous infusion in a doctor‚ ' s office. After the first dose, the patient receives a second dose 2 weeks later, and a third dose 6 weeks after that. After these three doses, the drug is given every 8 weeks.

Common side effects of infliximab include respiratory infections (sinus infections and sore throat), headache, rash, cough, and stomach pain. Like all anti-TNF drugs, inflixmab can potentially cause serious severe side effects, including increased susceptibility to viral, fungal, and bacterial infections (including tuberculosis). Other severe side effects may include lymphoma (a type of cancer), heart failure, liver failure, aplastic anemia, nervous system disorders, and allergic reactions.

In particular, opportunistic fungal infections and tuberculosis are serious concerns for patients who take anti-tumor necrosis factor (anti-TNF) drugs such as infliximab. Your doctor should carefully monitor you for any signs of infection. Symptoms of fungal infections include fever, malaise, weight loss, sweating, cough, and shortness of breath. If you experience any of these symptoms, contact your doctor.

Researchers are currently studying other biologic drugs for treatment of ulcerative colitis. These investigational drugs include adalimumab (Humira), which is approved for Crohn‚ ' s disease, and rituximab (Rituxan), basiliximab (Simulect), and golimumab (CNTO 148). To date, however, infliximab is the only biologic drug approved for treatment of ulcerative colitis.

Resources

References

Baumgart DC and Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369(9573):1641-57.

Chande N, MacDonald JK and McDonald JW. Methotrexate for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2007;(4):CD006618.

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006. Gastroenterology. 2007 Jul;133(1):312-39.

Langan RC, Gotsch PB, Krafczyk MA and Skillinge DD. Ulcerative colitis: diagnosis and treatment. Am Fam Physician. 2007; 76(9):1323-30.

Mahid SS, Minor KS, Soto RE, Hornung CA and Galandiuk S. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006;81(11):1462-71.

Mallon P, McKay D, Kirk S and Gardiner K. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2007;(4):CD005573.

  • Reviewed last on: 12/1/2008
  • Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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