Inflammatory Bowel Disease Medication

Updated: Oct 18, 2017
  • Author: William A Rowe, MD; Chief Editor: BS Anand, MD  more...
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Medication

Medication Summary

Many inflammatory mediators have been identified in inflammatory bowel disease (IBD); antibodies against these mediators and methods to block the production or receptors for these mediators hold great promise as potential therapy for IBD.

Therapy for Crohn disease is generally less effective than that for ulcerative colitis. In addition to the therapies outlined herein, IV cyclosporine or infliximab is helpful in refractory ulcerative colitis. A conventional stepwise approach may be taken. With this approach, the most benign (or temporary) drugs are used first. If they fail to provide relief, drugs from a higher step are used. However, more aggressive disease requires immunomodulator and biologic therapy earlier in the treatment program.

The stepwise approach is as follows:

  1. Aminosalicylates and symptomatic agents are step I drugs; antibiotics are step IA drugs, given the limited situations in which they are used

  2. Corticosteroids constitute the step II drugs, which are to be used if the step I drugs fail to adequately control the IBD

  3. Immune-modifying agents are step III drugs and are used if corticosteroids fail or are required for prolonged periods; infliximab and adalimumab are also step III drugs

  4. Step IV drugs are experimental agents, are used only after the previous steps fail, and are administered only by physicians familiar with their use

Note that drugs from all steps may be used additively; in general, the goal is to wean the patient off steroids as soon as possible to prevent long-term adverse effects from these agents. Opinions differ regarding the use of certain agents in this stepwise approach.

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5-Aminosalicylic Acid Derivatives

Class Summary

The 5-aminosalicylic acid (ASA) derivatives are effective in reducing inflammatory reactions. All of the aminosalicylates are useful for treating flares of mild to moderate ulcerative colitis and occasionally Crohn colitis and for maintaining remission.

Sulfasalazine (Azulfidine, Azulfidine EN-tabs, Sulfazine, Sulfazine EC)

Sulfasalazine is considered best for colonic disease, although it is also considered first-line therapy for Crohn disease. This agent is used for acute disease and for maintenance of remission.

Mesalamine (Asacol HD, Pentasa, Canasa, Rowasa, Lialda, Apriso, Delzicol)

Mesalamine is a 5-ASA that acts systemically and also has activity as a topical anti-inflammatory.

Balsalazide (Colazal, Giazo)

Balsalazide is a prodrug 5-ASA connected to a 4-aminobenzoyl-(beta)-alanine carrier by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA. Metabolites of the drug may decrease inflammation by blocking the production of arachidonic acid metabolites in colonic mucosa.

Olsalazine (Dipentum)

Olsalazine is useful for active disease and maintenance of remission in ulcerative colitis. Dipentum is a 5-ASA connected to a 5-ASA by an azo bond; colonic bacteria break the azo bond, releasing the active 5-ASA. Note that an adverse event of high ileal secretion of chloride creates a different type of diarrhea, which lessens its acceptability.

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Antibiotics, Other

Class Summary

Metronidazole (Flagyl) and ciprofloxacin (Cipro) are the most commonly used antibiotics in persons with inflammatory bowel disease (IBD). Antibiotics are less effective in persons with ulcerative colitis, except in fulminant toxic megacolon or pouchitis. Rifaximin (Xifaxan) is an FDA-approved broad-spectrum antibiotic that may also help treat patients with IBD.

Metronidazole (Flagyl, Flagyl ER, Metro)

Metronidazole is a widely available, inexpensive antibiotic and antiprotozoal agent. This agent inhibits protein synthesis and causes cell death in susceptible organisms by diffusing into the organism and causing a loss of helical DNA structure and strand breakage. Metronidazole's adverse-event profile includes headache, dysgeusia, and neuropathy.

Ciprofloxacin (Cipro, Cipro XR)

Ciprofloxacin is a fluoroquinolone antibiotic commonly used for the treatment of urinary, skin, and respiratory tract infections. This agent inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Caution is advised with the use of ciprofloxacin regarding tendon rupture.

Rifaximin (Xifaxan)

Rifaximin is a nonabsorbed (<0.4%), broad-spectrum antibiotic specific for enteric pathogens of the gastrointestinal tract (ie, gram-positive, gram-negative, aerobic, anaerobic). It is a rifampin structural analog and it binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis.

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Corticosteroids

Class Summary

Corticosteroid agents are the treatments of choice for an acute inflammatory bowel disease (IBD) attack; administer intravenously in severe disease. Administer increased or stress doses to patients already on steroids. Do not use steroids for maintaining IBD remission, because of their lack of efficacy and potential complications, including avascular bone necrosis, osteoporosis, cataracts, emotional lability, hypertension, diabetes mellitus, cushingoid features, acne, and facial hair. Cortenema, Cortifoam, and Anusol-HC suppositories are useful in treating distal disease (proctitis and proctosigmoiditis).

Hydrocortisone (Solu-Cortef, Cortef, A-Hydrocort )

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. Alternative adrenocortical steroids may be used in equivalent dosage.

Prednisone (Rayos)

Prednisone acts as a potent inhibitor of inflammation. It 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. Alternative corticosteroids may be used in equivalent dosage.

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

Adrenocortical steroids act as potent inhibitors of inflammation and may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to modification of the immune response. Alternative adrenocortical steroids may be used in equivalent dosage. Methylprednisolone has a greater salt- and water-retention side effect.

Prednisolone (Orapred, Pediapred, Millipred, Veripred 20, Flo-Pred)

Corticosteroids 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 modification of the immune response. Alternative corticosteroids may be used in equivalent dosage.

Budesonide (Entocort EC)

Budesonide alters the level of inflammation in tissues by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators involved in inflammatory reactions. Only 10% is bioavailable because of first-pass metabolism.

Dexamethasone (Baycadron, DoubleDex)

Dexamethasone has many pharmacologic benefits, but there are also significant adverse effects. It stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentrations, and inhibits prostaglandin and proinflammatory cytokines.

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Immunosuppressants

Class Summary

Immunosuppressant agents are useful as steroid-sparing agents, in healing fistulas, and in patients with serious contraindications to surgery. [104] These drugs are used in patients who are refractory to or unable to tolerate steroids and in patients in whom remission is difficult to maintain with the aminosalicylates alone. Azathioprine and its metabolite, 6-mercaptopurine (MP), are useful in Crohn disease complicated by recurrent rectal fistulas or perianal disease; however, the clinical response can take up to 6 months. Methotrexate has also been tried.

Azathioprine (Imuran, Azasan)

Azathioprine inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins; these effects may decrease the proliferation of immune cells and result in lower autoimmune activity.

6-Mercaptopurine (Purinethol, Purixan)

6-Mercaptopurine is a purine analog that inhibits DNA and RNA synthesis, causing arrest of cell proliferation.

Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo)

Methotrexate impairs DNA synthesis and induces the apoptosis and reduction in interleukin (IL)-1 production. It is indicated for moderate to severe disease and maintenance of remission. The onset of action is delayed.

Cyclosporine (Sandimmune, Neoral, Gengraf)

According to the American Gastroenterological Association (AGA) guidelines, intravenous cyclosporine is effective for avoiding surgery in patients with ulcerative colitis who have failed to respond to 7-10 days of high-dose oral or parenteral corticosteroids. Concomitant administration of IV corticosteroids is recommended in these cases.

Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-versus-host disease.

For children and adults, dosing is based on ideal body weight.

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TNF Inhibitors

Class Summary

Monoclonal antibodies targeted against tumor necrosis factor alpha (TNFα) interrupt endogenous TNF. Increased TNFα levels have been observed in Crohn disease and ulcerative colitis and are thought to be part of the pathogenesis of IBD. TNFα induces proinflammatory cytokines (eg, interleukins), enhances leukocyte migration, activates neutrophils and eosinophils, and induces enzymatic degradation.

This class includes adalimumab, certolizumab, golimumab, and infliximab. Infliximab and adalimumab are FDA approved for both Crohn disease and ulcerative colitis, whereas certolizumab is FDA approved only for Crohn disease and golimumab only for ulcerative colitis.

Infliximab was the first of this class for use in inflammatory bowel disease. [69] Infliximab is more effective against Crohn disease than ulcerative colitis. This drug promotes mucosal healing; heals perianal and enterocutaneous fistulas; and has been shown to reduce signs and symptoms, achieve clinical remission and mucosal healing, and eliminate corticosteroid use. [123] Infliximab is indicated for patients who have experienced inadequate response to conventional therapy. [104]

Infliximab (Remicade)

Infliximab neutralizes cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. It is mixed in 250 mL of normal saline and infused IV over 2 hours. It is indicated for both ulcerative colitis and Crohn disease.

Adalimumab (Humira)

Adalimumab is a TNF blocking agent that has been FDA approved for both Crohn disease and ulcerative colitis. It is administered by subcutaneous injection.

Adalimumab is recombinant human immunoglobulin (Ig) G1 monoclonal antibody specific for human TNF. It binds specifically to TNF-alpha and blocks the interaction with p55 and p75 cell-surface TNF receptors.

Certolizumab pegol (Cimzia)

Certolizumab is a TNF blocking agent that has been FDA approved for the treatment of Crohn disease but not for ulcerative colitis. It is administered by subcutaneous injection.

Certolizumab pegol is a pegylated antitumor necrosis factor (TNF)–alpha blocker, which results in disruption of the inflammatory process. It is indicated for moderate to severe Crohn disease in individuals whose condition has not responded to conventional therapies.

Golimumab (Simponi, Simponi Aria)

Human anti-TNF-alpha monoclonal antibody. Indicated for ulcerative colitis but not Crohn disease. It is administered by SC injection.

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Alpha 4 Integrin Inhibitors

Class Summary

Integrin inhibitors are emerging as options for moderate-to-severe 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 a recombinant humanized IgG4-1C monoclonal antibody produced in murine myeloma cells. It binds to alpha-4 subunits of α4β1 and α4β7 integrins expressed on the leukocyte surface, which inhibit α4-mediated leukocyte adhesion to their receptors. In Crohn disease, the interaction of the α4β7 integrin with the endothelial receptor MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of the disease.

Vedolizumab (Entyvio)

Vedolizumab is a recombinant humanized monoclonal antibody that binds specifically to α4β7 integrin. It blocks the interaction of α4β7 integrin with a gut-associated 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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Histamine H2 Antagonists

Class Summary

H2-receptor antagonists are reversible competitive blockers of histamines at the H2 receptors, particularly those in the gastric parietal cells, where they inhibit acid secretion. The H2 antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents.

Cimetidine (Tagamet)

Cimetidine inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Ranitidine (Zantac, Deprizine FusePaq)

Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Famotidine (Pepcid)

Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Nizatidine (Axid)

Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

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Proton Pump Inhibitors

Class Summary

Proton pump inhibitors (PPIs) reduce gastric acid secretion by inhibition of the H+ -K+ -ATPase enzyme system in the gastric parietal cells. These agents are used in patients with severe esophagitis and in patients whose disease is not responsive to H2-antagonist therapy.

Omeprazole (Prilosec)

Omeprazole decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATPase pump.

Lansoprazole (Prevacid)

Lansoprazole suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase enzyme system (ie, proton pump) at the secretory surface of the gastric parietal cell. It blocks the final step of acid production. The effect is dose-related and inhibits both basal and stimulated gastric acid secretion, thus increasing the gastric pH.

Esomeprazole magnesium (Nexium)

Esomeprazole magnesium is an S-isomer of omeprazole. It inhibits gastric acid secretion by inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Esomeprazole is used in severe cases and in patients not responding to H2-antagonist therapy. This agent is used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers; however, it may be used for up to 8 weeks to treat all grades of erosive esophagitis.

Rabeprazole sodium (Aciphex)

Rabeprazole sodium decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATPase pump.

Pantoprazole (Protonix)

Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells.

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Antidiarrheals

Class Summary

These agents provide symptomatic relief when patients report symptoms of diarrhea.

Diphenoxylate and atropine (Lomotil)

Diphenoxylate and atropine is a drug combination that acts as an antidiarrheal agent chemically related to the narcotic analgesic meperidine. This agent acts on intestinal muscles to inhibit peristalsis and slow intestinal motility, prolonging the movement of electrolytes and fluid through the bowel, and increasing the viscosity. A subtherapeutic dose of anticholinergic atropine sulfate is added to discourage overdosage, in which case diphenoxylate may clinically mimic the effects of codeine.

Loperamide (Imodium A-D, Diamode)

Loperamide acts on intestinal muscles to inhibit peristalsis and slow intestinal motility. It prolongs the movement of electrolytes and fluid through the bowel and increases viscosity.

Cholestyramine (Questran, Prevalite)

Cholestyramine may be used to treat diarrhea associated with excess bile acids. It binds bile acids, thus reducing the damage to the intestinal mucosa. Cholestyramine also reduces the induction of colonic fluid secretion and forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.

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Anticholinergic, Antispasmodic Agents

Class Summary

Anticholinergic antispasmodic agents are used to treat spastic disorders of the gastrointestinal tract.

Dicyclomine (Bentyl)

Dicyclomine is used to treat gastrointestinal motility disturbances. It blocks the action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and the central nervous system (CNS).

Hyoscyamine (Levbid, Levsin, Levsin-SL, HyoMax SL, Symax-SL, Symax-SR, NuLev, Oscimin)

Hyoscyamine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS, which, in turn, has antispasmodic effects. The sublingual (SL) tablets may be administered orally, sublingually, or chewed.

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