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Inflammatory Bowel Disease: Treatment & Medication
Updated: Nov 20, 2009
- Overview
- Differential Diagnoses & Workup
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Treatment
Emergency Department Care
- Initiate supportive care with bowel rest, nasogastric suction, and intravenous (IV) fluids containing electrolytes.
- Admit for toxicity, obstruction, hemorrhage, or localized peritonitis.
- Monitor severe cases for fat malabsorption.
- Treat perirectal disease.
- Sitz baths
- Soap and water after stooling
- Surgical drainage of perirectal abscesses
- Surgical treatment of recurrent fistulas if medical management fails
- Administer folate supplementation as needed.
Consultations
- Consult a surgeon for complicating obstruction, hemorrhage, perforation, abscess or fistula formation, toxic megacolon, or perianal disease.
- Consider surgical intervention for patients in whom medical therapy fails. The 2 most common choices today (for ulcerative colitis) are proctocolectomy with ileostomy and total colectomy with ileoanal anastomosis. Elective surgery can sometimes be performed laparoscopically. For fulminant colitis, the surgical procedure of choice consists of a subtotal colectomy with end ileostomy and creation of a Hartman pouch.
- In Crohn's disease, surgically resect only as much bowel as necessary to correct the problem because the recurrence rate after surgery approaches 100%.
- Patients with toxic megacolon initially require nasogastric suction and IV steroids. Failure to improve within 48 hours is an indication for total colectomy.
- Extracolonic manifestations (ie, uveitis, arthritis, dermatitis, sclerosing cholangitis) are best managed with the aid of specialty consultation.
Medication
Therapy for Crohn's disease generally is less effective than that for ulcerative colitis. In addition to the therapies outlined herein, intravenous cyclosporine is helpful in refractory ulcerative colitis. Zileuton, a 5-lipoxygenase inhibitor, has shown some efficacy in treating Crohn's disease.
Hyperbaric oxygen therapy may be helpful in the treatment of inflammatory bowel disease (IBD) that is unresponsive to other therapies. Its therapeutic efficacy appears to result from decreased generation of prostaglandin E2. Previous work has linked mucosal prostaglandin E2 to the intestinal damage associated with IBD.8
Agents for symptomatic treatment include loperamide and the combination of diphenoxylate and atropine, which are useful in mild disease to reduce the number of bowel movements and to relieve rectal urgency. Cholestyramine, a resin that binds bile salts, is useful for reducing diarrhea in patients with Crohn's disease who have had ileal resections. The anticholinergic agent dicyclomine may help relieve intestinal spasms. Antidiarrheal and anticholinergic medications must be avoided in acute severe disease because they may precipitate toxic megacolon. Avoid the long-term use of narcotics for pain. An iron supplement should be added when significant rectal bleeding is present.
Antidiarrheal agents
These agents inhibit peristalsis in the GI tract.
Loperamide (Imodium)
Acts in intestinal muscles to inhibit peristalsis and to slow intestinal motility. Prolongs movement of electrolytes and fluid through bowel; increases viscosity and loss of fluids and electrolytes.
Adult
Initial dose: 4 mg PO
Maintenance: 2 mg PO after each loose stool; not to exceed 16 mg/d
Pediatric
<2 years: Not established
2-6 years: 1 mg PO tid initially; followed by 0.1 mg/kg PO after each loose stool; not to exceed 1 mg tid
6-8 years: 2 mg PO bid initially; followed by 0.1 mg/kg PO after each loose stool; not to exceed 2 mg bid
8-12 years: 2 mg PO tid initially; followed by 0.1 mg/kg PO after each loose stool; not to exceed 2 mg tid
>12 years: Administer as in adults
Chronic diarrhea: 0.08-0.24 mg/kg/d PO divided bid/tid; not to exceed 2 mg/dose
Phenothiazines, tricyclic antidepressants, and CNS depressants may increase toxicity
Documented hypersensitivity; diarrhea resulting from infection; pseudomembranous colitis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue use if no clinical improvement is noted in 48 h; because metabolized primarily in liver, monitor for CNS toxicity in patients with hepatic insufficiency; do not use if high fever or blood in stool coincides with diarrhea
Diphenoxylate and Atropine (Lomotil)
Drug combination that consists of diphenoxylate, a constipating meperidine congener, and subtherapeutic amount of atropine to discourage abuse. Inhibits excessive GI propulsion and motility.
Adult
15-20 mg/d PO tid/qid; followed by 5-15 mg/d
Pediatric
<2 years: Not recommended
>2 years: 0.3-0.4 mg/kg/d PO divided qid
2-5 years: 2 mg PO tid
5-8 years: 2 mg PO qid
8-12 years: 2 mg PO 5 times/d
>12 years: Administer as in adults
May delay metabolism of drugs by liver; CNS depressants, MAOIs, and antimuscarinic agents may increase toxicity
Documented hypersensitivity; narrow-angle glaucoma; hepatic insufficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Dehydration may influence variability of response in young children, predisposing them to delayed diphenoxylate intoxication; caution in patients with UC; decrease in intestinal motility may be detrimental to patients with diarrhea resulting from Shigella and Salmonella species and toxigenic strains of Escherichia coli
Cholestyramine (Questran)
Useful in treating diarrhea associated with pseudomembranous colitis. Inhibits enterohepatic reuptake of intestinal bile salts by forming nonabsorbable complex with bile acids in intestine.
Adult
4 g PO qd/bid; not to exceed 24 g/d or 6 doses/d
Pediatric
240 mg/kg/d PO divided tid
Inhibits absorption of numerous drugs, including warfarin, thyroid hormone, amiodarone, NSAIDs, methotrexate, digitalis glycosides, glipizide, phenytoin, imipramine, niacin, methyldopa, tetracyclines, clofibrate, hydrocortisone, and penicillin G
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in constipation and phenylketonuria
Antispasmodic agents
These agents are used to treat functional disturbances of GI motility.
Dicyclomine (Bentyl)
Useful in treating GI motility disturbances; blocks action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle, and CNS.
Adult
80 mg/d PO divided qid initially, then increase to 160 mg/d
Pediatric
10 mg/dose PO tid/qid
Effects are weakened when administered with anti-Parkinson drugs, haloperidol, and phenothiazines; toxicity increases when administered concurrently with amantadine, antihistamines, type I antiarrhythmics, phenothiazines, TCAs, or narcotic analgesics
Documented hypersensitivity; myasthenia gravis; narrow-angle glaucoma
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution when administering to patients with hepatic or renal insufficiency, cardiovascular disease, urinary tract obstruction, UC, GI obstruction, hyperthyroidism, or hypertension
Aminosalicylates
These agents are effective for treating acute ulcerative colitis (UC) and for maintaining its remission; they are also beneficial in mildly to moderately active Crohn's disease (CD) when the colon is involved. Sulfasalazine has not been clearly shown to maintain remission in CD. Furthermore, there is some question as to its effectiveness versus small bowel disease.
Newer aminosalicylate preparations without sulfapyridine (eg, 5-aminosalicylic acid [5-ASA]) were developed because tolerance of sulfasalazine has been limited by the sulfa-containing moiety. Because free 5-ASA is absorbed rapidly from the proximal GI tract, it has been modified in the newer formulations. Olsalazine consists of two 5-ASA molecules linked together by an azo bond. Intestinal bacteria cleave the bond, which enables olsalazine to work, primarily in the colon.
Additional formulations of 5-ASA (mesalamine) are Asacol, Pentasa, Rowasa, and Balsalazide. Asacol is composed of 5-ASA coated in a pH-dependent acrylic resin, which allows delayed release of 5-ASA in the distal ileum and the right colon. Pentasa consists of 5-ASA encapsulated into microgranules of ethylcellulose and released continuously throughout the GI tract. Therefore, it is useful in patients with CD involvement of the small bowel and the colon. Rowasa contains 5-ASA in suppository or enema formulations, which are useful for treating and maintaining remissions in ulcerative proctitis and proctosigmoiditis. Balsalazide is mesalamine linked to an inert carrier molecule. In the colon, bacteria cleave the bond and release free mesalamine.
Because oral aminosalicylates interfere with folate absorption, folic acid supplementation (1 mg/d) should be given.
Sulfasalazine (Azulfidine)
Combination of 5-ASA or mesalamine and sulfapyridine. Taken PO, remains intact until it reaches terminal ileum and colon, where it is split by bacteria into its 2 moieties. Active portion appears to be 5-ASA, which inhibits prostaglandin synthesis; sulfa portion is absorbed and causes most adverse reactions. Abdominal discomfort common. Folate deficiency may result from competition between folate and sulfasalazine for absorption.
Adult
3-4 g PO qd in divided doses
Pediatric
<2 years: Not established
>2 years: 30 mg/kg PO divided qid
Decreases effects of iron, digoxin, and folic acid; increases effects of PO anticoagulants, PO hypoglycemic agents, and methotrexate
Documented hypersensitivity; GI or GU obstruction
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction
Olsalazine (Dipentum)
Alternate treatment for patients who do not tolerate sulfasalazine. Useful in maintaining remission in UC; exerts anti-inflammatory activity in UC.
Adult
500 mg PO bid
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Relatively high incidence of diarrhea may be dose related (unclear whether other underlying causes may contribute)
Mesalamine (Asacol, Pentasa, Rowasa, Canasa)
Treats mildly to moderately active UC.
Usual course of therapy in adults is 3-6 wk. Some patients may need concurrent PR and PO therapy.
Adult
Cap: 1 g PO qid
Tab: 800 mg PO tid
Rectal supp: Insert 1 PR bid
Pediatric
Not established
Decreases effects of iron, digoxin, and folic acid; mesalamine increases effect of PO anticoagulants, methotrexate, and PO hypoglycemic agents
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Elderly patients may have difficulty administering and retaining rectal suppositories; caution in renal or hepatic impairment
Corticosteroids
These agents are the treatments of choice for an acute inflammatory bowel disease (IBD) attack; administer IV in severe disease. Give increased or stress doses to patients already on steroids. Do not use steroids for maintaining remission because of their lack of efficacy9 and potential complications, including avascular 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).
Budesonide (Entocort EC), a synthetic corticosteroid, is available for Crohn's disease (CD) with ileal or ileocecal involvement.10 It is indicated for PO treatment to induce remissions of attacks of mild-to-moderate severity involving the ileum and/or ascending colon.9 The drug contains budesonide granules in an ethylcellulose matrix coated with a methacrylic acid polymer. The coating, which requires a pH more than 5.5 to dissolve, prevents release of the drug in the stomach. The ethylcellulose matrix delays release further until the drug reaches the ileum and ascending colon. A potential advantage is that fewer adverse effects occur than with the use of systemic corticosteroids. However, some absorption occurs and may slow growth in adolescents.
Prednisone (Sterapred)
Used as immunosuppressant in treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
5-60 mg/d PO qd or divided bid/qid
Pediatric
4-5 mg/m2/d PO; alternatively, 1-2 mg/kg PO qd; not to exceed 60 mg/d; taper over 2 wk as symptoms resolve
Estrogens may decrease clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur
Methylprednisolone (Adlone, Medrol, Solu-Medrol)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and increasing permeability or capillaries.
Adult
125-250 mg IV loading dose, followed by maintenance dose of 0.5-1 mg/kg/dose IV q6h for up to 5 d
Pediatric
2 mg/kg IV loading dose, followed by maintenance dose of 0.5-1 mg/kg/dose IV q6h for up to 5 d
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications
Hydrocortisone (Anusol-HC, Anuprep HC)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
10-100 mg PR qd/bid for 2-3 wk
Pediatric
Not established
Clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific UC, diabetes mellitus, and myasthenia gravis
Immunosuppressants
These agents are useful as steroid-sparing agents, in healing fistulas, or when the patient has serious contraindications to surgery.9 They are used in patients refractory to or unable to tolerate steroids. Some agents, including azathioprine and its metabolite, 6-mercaptopurine, have been useful in Crohn's disease (CD) complicated by recurrent rectal fistulas or perianal disease; response can take up to 6 months. Methotrexate has also been tried.
Azathioprine (Imuran)
Inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins; these effects may decrease proliferation of immune cells and result in lower autoimmune activity.
Adult
1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg PO q4wk until response noted; not to exceed 2.5 mg/kg/d
Pediatric
Initial dose: 2-5 mg/kg/d PO/IV
Maintenance dose: 1-2 mg/kg/d PO
Allopurinol increases toxicity; ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxic effects may occur; check TPMT level before therapy and monitor liver, renal, and hematologic functions; pancreatitis is rarely associated
Antibiotics
Institute parenteral antibiotics active against coliforms and anaerobes for fulminant disease, including toxic megacolon. Agents may include metronidazole or ampicillin or a cephalosporin and an aminoglycoside.
Metronidazole (Flagyl)
Useful in treating fulminant disease; used successfully in CD complicated by perianal ulcers and perirectal abscesses and fistulas; unclear whether drug is active because of its antibacterial properties or through some other mechanism.
Adult
20 mg/kg/d PO in divided doses
Pediatric
Not established
May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction may occur with orally ingested ethanol
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse reactions include peripheral neuropathy, possible carcinogenesis, and mutagenesis; adjust dose in patients with severe hepatic disease (may metabolize metronidazole slowly); monitor patients for seizures and development of peripheral neuropathy
Tumor necrosis inhibitors
Infliximab (Remicade), given intravenously, consists of monoclonal antibodies to TNF-alpha. Infliximab is approved by the FDA for use in IBD.11 Infliximab is somewhat more effective against CD than UC. The drug appears to promote mucosal healing, which not even prednisone does. Furthermore, it heals perianal and enterocutaneous fistulae and has been shown to reduce signs and symptoms, achieve clinical remission and mucosal healing, and eliminate corticosteroid use.12 Infliximab is indicated for patients who have experienced inadequate response to conventional therapy.9
Etanercept (Enbrel) is a TNF receptor fusion protein that binds to TNF-alpha and TNF-beta, blocking their interaction with TNF receptors. Although it is approved for the treatment of moderate-to-severe rheumatoid arthritis, it has also been used investigationally for CD, although such use is not yet approved. Etanercept can cause an increased risk of infections, which can be serious and life threatening.
Certolizumab pegol (Cimzia)
Pegylated anti-TNF–alpha blocker, which results in disruption of the inflammatory process. Indicated for moderate-to-severe Crohn disease in individuals who have not responded to conventional therapies.
Adult
400 mg SC initially; repeat at weeks 2 and 4; if favorable response occurs, initiate maintenance dose of 400 mg SC q4wk
Administer as 2 separate 200-mg SC injections at 2 separate sites in abdomen or thigh
Pediatric
Not established
May interfere with immune response to live-virus vaccines (eg, MMR) and may reduce efficacy; coadministration with anakinra (an interleukin-1 antagonist that also blocks TNF) may cause additive adverse effects, particularly development of serious infections; may interfere with activated partial thromboplastin time tests
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Common adverse effects include headache, upper respiratory tract infections, abdominal pain, injection site reactions, and nausea; increases risk of serious infections, including infections that may result in hospitalization or death; may increase risk of opportunistic infections (eg, tuberculosis, invasive fungal), so test for latent tuberculosis, and, if positive, initiate tuberculosis treatment prior to starting certolizumab; if infection occurs, patients should contact their physician immediately; may cause reactivation of hepatitis B virus; may increase risk of lymphoma and other malignancies because of immune suppression; anaphylaxis or serious allergic reactions, demyelinating disease, cytopenias, pancytopenia, heart failure, and lupuslike syndrome have been reported with TNF blockers
Infliximab (Remicade)
Neutralizes cytokine TNF-alpha and inhibits binding to TNF-alpha receptor.
Adult
5 mg/kg IV as single infusion
When long-term administration is needed, an induction dose of 5 mg/kg IV infusion at 0, 2, and 6 wk is administered, then 5 mg/kg q8wk for maintenance
IV infusion must be administered over at least 2 h; must use infusion set with in-line, sterile, nonpyrogenic, low-protein-binding filter (pore size <1.2 µm)
Pediatric
Induction: 5 mg/kg IV infusion; repeat for a total of 3 doses at 2, and 6 wk
Maintenance: 5 mg/kg IV infusion q6wk
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; chest pain or rash may occur during infusion; more cases of lymphoma were observed in TNF alpha-blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections
More on Inflammatory Bowel Disease |
| Overview: Inflammatory Bowel Disease |
| Differential Diagnoses & Workup: Inflammatory Bowel Disease |
 Treatment & Medication: Inflammatory Bowel Disease |
| Follow-up: Inflammatory Bowel Disease |
| Multimedia: Inflammatory Bowel Disease |
| References |
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Further Reading
Keywords
IBD, inflammatory bowel disease, IBD symptoms, IBD diagnosis, IBD treatment, ulcerative colitis, Crohns, Crohn disease, Crohn's disease, regional enteritis, terminal ileitis, granulomatous ileocolitis, inflammation of the colon, colitis, irritable bowel syndrome, mucous colitis, spastic colon
