Crohn Disease Medication

Updated: Jan 06, 2017
  • Author: Leyla J Ghazi, MD; Chief Editor: Praveen K Roy, MD, AGAF  more...
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Medication

Medication Summary

The goals of pharmacotherapy in patients with Crohn disease are to reduce morbidity, to prevent complications, and to maintain nutritional status.

Management of diarrhea

Chronic diarrhea in Crohn disease responds well to antidiarrheal agents such as loperamide (2-4 mg), diphenoxylate with atropine (1 tablet), and tincture of opium (8-15 drops). Such agents may be administered up to 4 times daily, but they should not be given to patients with active colitis, because of the risk of developing toxic megacolon.

Patients with terminal ileal disease may not absorb bile acids normally, which can lead to secretory diarrhea in the colon. These patients may benefit from bile acid sequestrants such as cholestyramine (2-4 g) and colestipol (5 g 2 or 3 times daily before meals).

Abdominal cramps may be reduced with propantheline (30 mg before meals and at bedtime), dicyclomine (10-20 mg), or hyoscyamine (0.125 mg). These drugs should not be used if there is the possibility of a bowel obstruction.

Management of bowel inflammation

For colon and small bowel inflammation, anti-inflammatory drugs or antibiotics are helpful. Neither sulfasalazine nor balsalazide alleviates small bowel disease. Products such as mesalamine, which releases 5-aminosalicylic acid (5-ASA) in the distal small bowel secondary to pH changes are more useful in patients with small intestinal Crohn disease.

According to a systematic review, antituberculosis therapy, macrolides, fluoroquinolones, 5-nitroimidazoles, and rifaximin (alone or in combination) have been shown to induce remission in active Crohn disease and ulcerative colitis. [143] Further trials of antibiotic therapy are necessary in order to determine the best course of single or combination antibiotic therapy.

Long-term maintenance with mesalamine (800 mg 3 times daily) may delay clinical relapse. Prednisone (40-60 mg/day) is generally helpful in acute inflammation. Oral glucocorticoid preparations such as budesonide are useful for patients with isolated terminal ileal inflammation and may reduce systemic side effects.

Steroids are not indicated for maintenance therapy, because of serious complications, such as aseptic necrosis of the hip, osteoporosis, cataract, diabetes, and hypertension. Accordingly, once remission is achieved, the agent is slowly tapered (5-10 mg every 1-2 weeks).

If steroid withdrawal proves difficult, immunosuppressants such as azathioprine (2 mg/kg/day) or its active metabolite, 6-mercaptopurine (6-MP), may be considered. Response is usually observed within 3-6 months. Mycophenolate mofetil 500 mg twice daily in 2 divided doses is well tolerated by patients and can be used to reduce the steroid dose. [2, 82]

Management of fistulae

Fistulae between bowel loops (eg, ileoileal, ileocecal, or ileosigmoid) are usually benign and may not produce any major problems. Medical management is used to treat underlying infections and symptoms with oral metronidazole (1 g/day) for at least 1-2 months.

Infliximab is effective in patients who have refractory perianal and enterocutaneous fistulae. Current clinical practice is to give it 5 mg/kg by intravenous (IV) infusion at 0 weeks, 2 weeks, and 6 weeks, followed by maintenance IV infusions every 8 weeks. On average, the effect lasts for 12 weeks.

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5-Aminosalicylic Acid Derivatives

Class Summary

The 5-ASA derivative agents are used to treat mild-to-moderate Crohn disease and to maintain remission.

Mesalamine rectal (Canasa, Rowasa)

Rectal mesalamine is a formulation of mesalamine that specifically releases 5-ASA in the distal colon. This agent elicits an anti-inflammatory effect by an unknown mechanism.

Mesalamine (Asacol, Lialda, Apriso)

Products such as mesalamine, which releases 5-ASA in the distal small bowel secondary to pH changes, are more useful in patients with small intestinal Crohn disease. Long-term maintenance with mesalamine may delay clinical relapse. This agent is better tolerated than sulfasalazine and has fewer adverse effects.

Sulfasalazine (Azulfidine)

Sulfasalazine is useful mainly in colonic disease because the active compound, 5-ASA, is released in the large bowel by bacterial degradation of the parent compound. Sulfasalazine does not alleviate small bowel disease; it acts locally in the colon to reduce the inflammatory response and systemically inhibits prostaglandin synthesis. It has no additive or steroid-sparing effects when used in conjunction with corticosteroids. In contrast to its action in ulcerative colitis, sulfasalazine does not seem to maintain remission in Crohn disease.

Balsalazide (Colazal)

Balsalazide is an active component of sulfasalazine and is metabolized to mesalamine by intestinal flora. It has an anti-inflammatory effect, but its exact mechanism of action is not known. Balsalazide is used to treat ulcerative colitis.

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Corticosteroids

Class Summary

Corticosteroids are used to treat active moderate to severe Crohn disease. They are not indicated for maintenance therapy. A short course of corticosteroid therapy is indicated in patients with severe systemic symptoms (eg, fever, nausea, and weight loss) and in those whose condition does not respond to anti-inflammatory agents.

Budesonide is available in an ileal controlled-release form and is used for the treatment of ileal or right-side colonic disease. Budesonide induces remission in active Crohn disease but is less effective than other standard glucocorticosteroids and is of no benefit in preventing relapse. [86]

Prednisone

Prednisone exerts anti-inflammatory effects through decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decrease of production of eicosanoids, and stabilization of lysosomal membranes. This agent is generally helpful in acute inflammation.

Methylprednisolone (Solu-Medrol, Medrol, Depo-Medrol)

Methylprednisolone exercises anti-inflammatory effects through decreased capillary permeability, impaired neutrophil chemotaxis, release of anti-inflammatory cytokines, decreased production of eicosanoids, and stabilization of the lysosomal membrane.

Budesonide (Entocort EC)

Budesonide alters levels of inflammation in tissues by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in inflammatory reactions.

Hydrocortisone (Cortenema, Anusol-HC, Cortifoam)

Adrenocortical steroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body.

Prednisolone (Pediapred, Prelone, Orapred)

Prednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It is a commonly used oral agent. Prednisolone is used for an oral taper of steroids, which may reduce the emotional effects of steroid withdrawal and the risk of the development of adrenocortical insufficiency. However, these risks are not very high after only 3 days of treatment with high-dose steroids, and most neurologists do not use a prednisone taper.

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Immunosuppressants

Class Summary

Immunosuppressant agents are used off label to treat moderate-to-severe Crohn disease, to treat steroid-dependent or steroid-refractory disease, and to maintain remission.

Mercaptopurine (Purinethol)

6-MP and its prodrug azathioprine are purine analogues; they interfere with protein synthesis and nucleic acid metabolism and have cytotoxic effect on lymphoid cells. If steroid withdrawal proves difficult, immunosuppressants such as 6-MP may be considered.

Azathioprine (Imuran, Azasan)

Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which lowers autoimmune activity.

Methotrexate (Trexall, Rheumatrex)

Methotrexate is used for the treatment of moderate-to-severe Crohn disease and maintenance of remission. It is effective in inducing and maintaining remission in chronic Crohn disease in adults and has been shown to be effective and well tolerated for maintenance of remission in children. Methotrexate is a structural analogue of folic acid that inhibits binding of dihydrofolic acid to the enzyme dihydrofolate reductase. It impairs DNA synthesis, induces apoptosis, and reduces interleukin (IL)-1 production.

Tacrolimus (Prograf, Hecoria)

Tacrolimus is an immunomodulator produced by the bacteria Streptomyces tsukubaensis. Its mechanism of action is similar to that of cyclosporine. Tacrolimus may be effective in treating Crohn disease.

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Monoclonal Antibodies

Class Summary

Monoclonal antibodies are used in the treatment of moderate-to-severe active Crohn disease or fistulizing disease that is unresponsive to other medical therapy.

Infliximab (Inflectra, Remicade)

Infliximab is a chimeric mouse-human monoclonal antibody against tumor necrosis factor (TNF)-α that shows promise in the treatment of Crohn disease. This agent blocks TNF-α in the serum and at the cell surface, leading to the lysis of TNF-producing macrophages and T cells. Infliximab has been approved for the treatment of pediatric Crohn disease.

Adalimumab (Humira, Amjevita, adalimumab-atto)

Adalimumab is indicated for the induction and remission of moderate-to-severe active inflammatory Crohn disease. This agent is a recombinant human immunoglobulin (Ig) G1 monoclonal antibody specific for human TNF. It binds specifically to TNF-α and blocks interaction with p55 and p75 cell-surface TNF receptors. This interferes with the cytokine driven inflammatory processes. Adalimumab also lyses surface TNF-expressing cells in vitro in the presence of complement, but it does not bind to TNF-β (lymphotoxin).

Certolizumab pegol (Cimzia)

Certolizumab pegol is indicated for moderate-to-severe Crohn disease in individuals whose condition has not responded to conventional therapies. It is a pegylated anti–TNF-α blocker, and its action results in disruption of the inflammatory process.

Ustekinumab (Stelara)

Ustekinumab inhibits interleukin (IL)-12 and IL-23 cytokines, which play a key role in inflammatory and immune responses. It is indicated for adults with moderately to severely active Crohn disease who have failed or were intolerant to immunomodulators or corticosteroids, but never failed treatment with a tumor necrosis factor (TNF) blocker. It is also indicated for those who failed or were intolerant to treatment with 1 or more TNF blockers.

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Alpha 4 Integrin Inhibitors

Class Summary

Integrin inhibitors are emerging as options for moderate-to-severe active IBD in patients who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.

Natalizumab (Tysabri)

Natalizumab is indicated for moderate-to-severe Crohn disease in patients who have had inadequate responses to other therapies. It is a monoclonal antibody that binds α4β7 and α4β1 that results in inhibition of leukocyte adhesion and migration to areas of inflammation.

Vedolizumab (Entyvio)

Vedolizumab is a recombinant humanized monoclonal antibody that binds specifically to α4β7 integrin. It blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. It is indicated for both ulcerative colitis and Crohn disease.

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Antibiotics

Class Summary

Antibiotics are used in the treatment of mild-to-moderate, fistulizing, and perianal disease. Antibiotics may change the microbial flora of the intestine and have a potential effect on the cell-mediated immune system.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring–based antibiotic that is active against various anaerobic bacteria and protozoa. It is sometimes used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis). Metronidazole also possesses immunosuppressive and anti-inflammatory properties.

Ciprofloxacin (Cipro)

A fluoroquinolone, ciprofloxacin has activity against pseudomonads, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, and most gram-negative organisms, but it has no activity against anaerobes. Ciprofloxacin inhibits bacterial DNA synthesis and, consequently, growth.

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Antidiarrheals

Class Summary

Chronic diarrhea in Crohn disease responds well to antidiarrheal agents such as loperamide (2-4 mg), diphenoxylate with atropine (1 tablet), and tincture of opium (8-15 drops). Such agents may be administered up to 4 times daily, but they should not be given to patients with active colitis, because of the risk of developing toxic megacolon.

Loperamide (Imodium, Diamode)

Loperamide, which is available over the counter, acts on intestinal muscles to inhibit peristalsis and to slow intestinal motility. It prolongs the movement of electrolytes and fluid through the bowel and increases the viscosity and loss of fluids and electrolytes. Loperamide improves stool frequency and consistency, reduces abdominal pain and fecal urgency, and may exacerbate constipation.

Diphenoxylate-atropine (Lomotil)

The combination of diphenoxylate with atropine consists of 2.5 mg of diphenoxylate, which is a constipating meperidine congener, and 0.025 mg of atropine to discourage abuse. The preparation inhibits excessive gastrointestinal (GI) propulsion and motility, but it may exacerbate constipation.

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Bile Acid Sequestrants

Class Summary

Patients with terminal ileal disease may not absorb bile acids normally, which can lead to secretory diarrhea in the colon. These patients may benefit from bile acid sequestrants such as cholestyramine and colestipol.

Cholestyramine (Prevalite, Questran, Questran Light)

Cholestyramine is used for diarrhea associated with Crohn disease. It binds bile acids, thereby reducing damage to the intestinal mucosa. Cholestyramine also reduces the induction of colonic fluid secretion. It forms a nonabsorbable complex with bile acids in the intestine, thereby, in turn, inhibiting enterohepatic reuptake of intestinal bile salts.

Colestipol (Colestid)

Colestipol forms a soluble complex after binding to bile acid, increasing fecal loss of bile acid–bound low-density lipoprotein cholesterol.

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Anticholinergic Agents

Class Summary

Abdominal cramps may be reduced with anticholinergic agents such as propantheline, dicyclomine, or hyoscyamine. These drugs should not be used if there is the possibility of a bowel obstruction.

Dicyclomine (Bentyl)

Dicyclomine treats GI motility disturbances. It blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and the central nervous system (CNS). Adverse effects are dose-dependent.

Hyoscyamine (Levsin, Levbid, Anaspaz, Symax, NuLev)

Hyoscyamine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, thereby exerting antispasmodic effects. This agent decreases fecal urgency and pain.

Propantheline

Propantheline is a quaternary ammonium antimuscarinic agent with peripheral effects that are similar to those of atropine. It inhibits GI motility and decreases gastric acid secretion.

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