“AHFS is my favorite resource and usually my fi rst entry

point for drug information. ” David Hardy, B.S., M.S., V.P. Virginia Mason/ Health Resource Services

Page 1 of 11

given omeprazole 20 or 40 mg daily compared with patients given ranitidine 150 mgtwice daily. Ulcer healing rates averaged 83 or 53% at 2 weeks, 97–100 or 82% at 4weeks, and 100 or 94% at 8 weeks with the omeprazole regimens or ranitidine 150 mgtwice daily, respectively. In several studies, ulcer healing was less likely in patientswho were smokers and in those with large ulcers than in other patients.

Most patients with duodenal ulcer respond to omeprazole therapy during the initial4-week course of therapy; an additional 4 weeks of therapy may contribute to healingin some patients.

Omeprazole delayed-release capsules and omeprazole magnesium delayed-releaseoral suspension are used in combination with clarithromycin and amoxicillin (tripletherapy) for the treatment of H. pylori infection and duodenal ulcer disease in adults.Omeprazole delayed-release capsules and omeprazole magnesium delayed-releaseoral suspension also are used in combination with clarithromycin (dual therapy) inadults for the treatment of H. pylori infection and duodenal ulcer disease. Omeprazolealso has been used in other multiple-drug regimens† for the treatment of H. pyloriinfection associated with peptic ulcer disease. Current epidemiologic and clinicalevidence supports a strong association between gastric infection with H. pylori andthe pathogenesis of duodenal and gastric ulcers; long-term H. pylori infection also hasbeen implicated as a risk factor for gastric cancer. For additional information on theassociation of this infection with these and other GI conditions, see Helicobacter pyloriInfection, under Uses, in Clarithromycin 8:12.12.92. Conventional antiulcer therapywith histamine H2-receptor antagonists, proton-pump inhibitors, sucralfate, and/orantacids heals ulcers but generally is ineffective in eradicating H. pylori, and such

therapy is associated with a high rate of ulcer recurrence (e.g., 60–100% per year). TheAmerican College of Gastroenterology (ACG), the National Institutes of Health (NIH),

patients with initial or recurrent infection receive anti-infective

therapy for treatment of the infection. Although 3-drug regimens consisting of abismuth salt (e.g., bismuth subsalicylate) and 2 anti-infective agents (e.g., tetracyclineor amoxicillin plus metronidazole) administered for 10–14 days have been effectivein eradicating the infection, resolving associated gastritis, healing peptic ulcer, and

-associated peptic ulcerdisease, current evidence principally from studies in Europe suggests that 1 week of

eradication rates. Other regimens thatcombine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with abismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, histamine

eradication,and the choice of a particular regimen should be based on the rapidly evolving data onoptimal therapy, including consideration of the patient’s prior exposure to anti-infectiveagents, the local prevalence of resistance, patient compliance, and costs of therapy.

regimens containing 2 anti-infectivesenhances effectiveness, and limited data suggest that such regimens retain goodefficacy despite imidazole (e.g., metronidazole) resistance. Therefore, the ACG andmany clinicians currently recommend 1 week of therapy with a proton-pump inhibitorand 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole),

infection.Therapy with an antisecretory drug and a single anti-infective agent (i.e., “dual

regimens(e.g., clarithromycin-omeprazole, ranitidine bismuth citrate-omeprazole, amoxicillin-

infection and prevent recurrence ofduodenal ulcer at least in the short term (e.g., at 6 months following completion of

H. pyloriregimens consisting of at least 3 drugs (e.g., 2 anti-infective agents plus a proton-

eradication rates,decreased failures due to resistance, and shorter treatment periods compared withthose apparently required with 2-drug regimens. Additional randomized, controlled

regimens are needed to clarify optimum infection. For a

infection, including details about the efficacyof various regimens and rationale for drug selection, see Uses: Helicobacter pylori

Omeprazole immediate- and delayed-release capsules, omeprazole immediate-release oral suspension, and omeprazole magnesium delayed-release oral suspensionare used in adults for the short-term treatment and symptomatic relief of active benigngastric ulcer. In controlled studies in patients with endoscopically confirmed gastriculcers, reported rates of ulcer healing with omeprazole therapy were substantiallyhigher than those with placebo. In a multicenter, double-blind study in patients withendoscopically confirmed gastric ulcer, reported rates of ulcer healing with omeprazole20 or 40 mg daily or placebo were 48, 56, or 31%, respectively, at 4 weeks and 75, 83,or 48%, respectively, at 8 weeks. In patients with an ulcer larger than 1 cm in size, thepercentage of patients with healed ulcers at 8 weeks was greater with the 40-mg dosagethan with the 20-mg dosage of omeprazole. Otherwise, for patients with smaller ulcers,no difference in ulcer healing rates between the 40- and 20-mg dosages was observed.

In a multicenter, comparative study in patients with endoscopically confirmedgastric ulcer, ulcer healing occurred at 4 weeks in 64 or 78% of patients receivingomeprazole 20 or 40 mg daily, respectively, compared with 56% of those receivingranitidine 150 mg twice daily; at 8 weeks, 82, 91, or 78% of patients receivingomeprazole 20 mg daily, omeprazole 40 mg daily, or ranitidine 150 mg twice daily,respectively, had healed ulcers.■ Crohn’s Disease-associated Ulcers

Although evidence currently is limited, proton-pump inhibitors have been usedfor gastric acid-suppressive therapy as an adjunct in the symptomatic treatment ofupper GI Crohn’s disease†, including esophageal, gastroduodenal, and jejunoilealdisease. The drugs have been used for symptomatic relief of upper GI symptoms and topromote healing of Crohn’s disease-associated peptic ulcer disease. Most evidence ofefficacy to date has been from case studies in patients with Crohn’s-associated pepticulcer disease unresponsive to other therapies (e.g., histamine H2-receptor antagonists,cytoprotective agents, antacids, and/or sucralfate). Omeprazole (20 or 40 mg daily)was associated with resolution of symptoms and ulcer healing within about 2 and 4weeks, respectively, in some patients, while others required several months of acid-suppressive therapy. Subsequent symptomatic relief may be maintained with prolongedacid-suppressive therapy with a proton-pump inhibitor or H2-receptor antagonist, withor without an immunosuppressive agent (e.g., azathioprine). Adjunctive inhibition

Page 2 of 4

Dosage and Administration■ General

Tofacitinib therapy should not be initiated in patients with a lymphocyte count ofless than 500/mm3, an absolute neutrophil count (ANC) of less than 1000/mm3, or ahemoglobin concentration of less than 9 g/dL.

Methotrexate, other nonbiologic disease-modifying antirheumatic drugs(DMARDs), nonsteroidal anti-inflammatory agents (NSAIAs), and corticosteroidsmay be continued in patients receiving tofacitinib for the management of rheumatoidarthritis.

Concomitant use of tofacitinib with potent inducers of cytochrome P-450 (CYP)isoenzyme 3A4 (e.g., rifampin) may result in loss of or reduced clinical response totofacitinib.■ Administration

Tofacitinib citrate is administered orally without regard to meals.■ Dosage

Dosage of tofacitinib citrate is expressed in terms of tofacitinib.Rheumatoid Arthritis in Adults

For the management of rheumatoid arthritis in adults who have had an inadequateresponse or intolerance to methotrexate, the recommended dosage of tofacitinib is 5mg twice daily.

In patients receiving concomitant therapy with potent inhibitors of CYP3A4 (e.g.,ketoconazole) and in patients receiving concomitant therapy with one or more drugsthat result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19(e.g., fluconazole), dosage of tofacitinib should be reduced to 5 mg once daily.Treatment Interruptions for Toxicity

If a serious infection develops, tofacitinib therapy should be interrupted until theinfection has been controlled.

Tofacitinib therapy also should be interrupted or discontinued in patients withlymphopenia, neutropenia, or anemia.

Patients with a lymphocyte count of at least 500/mm3 may continue to receive therecommended dosage of tofacitinib. In patients who develop a lymphocyte count ofless than 500/mm3 (confirmed by repeat testing), tofacitinib should be discontinued.

Patients with an ANC exceeding 1000/mm3 may continue to receive therecommended dosage of tofacitinib. In patients with a persistent decrease in ANC to500–1000/mm3, tofacitinib therapy should be interrupted until the ANC exceeds 1000/mm3; tofacitinib therapy then may be resumed at the usual dosage of 5 mg twice daily.Tofacitinib therapy should be discontinued in patients with an ANC of less than 500/mm3 (confirmed by repeat testing).

Patients with a decrease in hemoglobin concentration of no more than 2 g/dLwhen the concentration value does not fall below 9 g/dL may continue to receivethe recommended dosage of tofacitinib. In patients with a decrease in hemoglobinconcentration of more than 2 g/dL or with a hemoglobin concentration of less than 8g/dL (confirmed by repeat testing), tofacitinib therapy should be interrupted until thehemoglobin concentration has normalized.■ Special Populations

Tofacitinib should not be used in patients with severe hepatic impairment. Dosageof tofacitinib should be reduced to 5 mg once daily in patients with moderate or severerenal impairment and in patients with moderate hepatic impairment. Administrationof supplemental doses of tofacitinib following dialysis is not necessary. Dosageadjustment is not necessary in patients with mild renal or hepatic impairment. Inaddition, dosage adjustments based on body weight, ethnicity, gender, or age are notrequired.

Cautions■ Contraindications

The manufacturer states that there are no known contraindications to the use oftofacitinib.■ Warnings/PrecautionsWarnings

Infectious Complications.Patients receiving tofacitinib are at increased risk of developing serious infections

that may require hospitalization or result in death. Opportunistic infections causedby bacterial, mycobacterial, invasive fungal, viral, or other opportunistic organisms—including cryptococcosis, pneumocystosis, tuberculosis and other mycobacterialinfections, esophageal candidiasis, multidermatomal herpes zoster, cytomegalovirusinfection, and BK virus infection—have been reported in patients with rheumatoidarthritis receiving tofacitinib. Patients with invasive fungal infections may presentwith disseminated, rather than localized, disease. Patients should be closely monitoredduring and after treatment with tofacitinib for the development of signs or symptomsof infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonaryinfiltrates, serious systemic illness including shock). Most patients who developed

serious infections were receiving concomitant therapy with immunosuppressive agentssuch as methotrexate or corticosteroids.

In controlled clinical trials in patients with rheumatoid arthritis, the overallfrequency of infections during the first 3 months of treatment was 20, 22, or 18%in patients receiving tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, orplacebo, respectively. Serious infections were reported at a rate of 1.7 events per100 patient-years in tofacitinib-treated patients and 0.5 events per 100 patient-yearsin placebo-treated patients during the first 3 months of therapy. The rate of seriousinfections during the first 12 months of tofacitinib therapy was 2.7 events per 100patient-years. The most common serious infections reported in patients receivingtofacitinib included pneumonia, cellulitis, herpes zoster, and urinary tract infection.Other serious infections (e.g., histoplasmosis, coccidioidomycosis, listeriosis),although not reported in clinical trials, also may occur in patients receiving tofacitinib.

Tofacitinib therapy should not be initiated in patients with active infections,including localized infections. Tofacitinib should be discontinued in patients whodevelop a serious infection, opportunistic infection, or sepsis and should not beresumed until the infection is controlled. Clinicians should consider potential risks andbenefits of tofacitinib prior to initiating therapy in patients with a history of chronic,recurring, serious, or opportunistic infections; patients with underlying conditions thatmay predispose them to infections; and patients who have been exposed to tuberculosisor who reside or have traveled in regions where tuberculosis or mycoses are endemic.Any patient who develops a new infection while receiving tofacitinib should undergoa thorough diagnostic evaluation (appropriate for an immunocompromised patient),appropriate anti-infective therapy should be initiated, and the patient should be closelymonitored.

Because tuberculosis has been reported in patients receiving tofacitinib, all patientsshould be evaluated for active or latent tuberculosis and for the presence of risk factorsfor tuberculosis prior to and periodically during therapy with the drug. When indicated,an appropriate antimycobacterial regimen for the treatment of latent tuberculosisinfection should be initiated prior to tofacitinib therapy. Antimycobacterial therapyalso should be considered prior to initiation of tofacitinib in individuals with a historyof latent or active tuberculosis in whom an adequate course of antimycobacterialtherapy cannot be confirmed and in individuals with a negative tuberculin skin testwho have risk factors for tuberculosis. Consultation with a tuberculosis specialist isrecommended when deciding whether antimycobacterial therapy should be initiated.Patients receiving tofacitinib, including individuals with a negative tuberculin skin test,should be monitored for signs and symptoms of active tuberculosis, which may presentwith pulmonary or extrapulmonary disease.

Viral reactivation can occur in patients receiving tofacitinib. Herpes zosterreactivation has been reported in patients receiving the drug. The effect of tofacitinibon the risk of reactivation of chronic viral hepatitis is not known; patients withserologic evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infectionwere excluded from clinical trials of tofacitinib.

Malignancies and Lymphoproliferative Disorders.Lymphoma and other malignancies have been observed in patients receiving

tofacitinib. In addition, an increased incidence of Epstein Barr virus (EBV)-associatedposttransplant lymphoproliferative disorder has been observed in renal allograftrecipients receiving tofacitinib concomitantly with immunosuppressive agents.

Among 3328 patients with rheumatoid arthritis receiving tofacitinib with or withoutother disease-modifying antirheumatic drugs (DMARDs) in clinical trials, 11 solidtumors and one lymphoma were diagnosed during the first 12 months of treatmentcompared with no cases of solid tumors or lymphoma in 809 patients receivingplacebo with or without other DMARDs. Lymphomas and solid tumors also have beenobserved in long-term extension studies in patients with rheumatoid arthritis receivingtofacitinib.

In controlled clinical trials in patients with rheumatoid arthritis, malignancies(excluding nonmelanoma skin cancer) were reported at a rate of 0.3 events per100 patient-years in tofacitinib-treated patients and 0 events per 100 patient-yearsin placebo-treated patients during the first 3 months of treatment. The rate ofmalignancies (excluding nonmelanoma skin cancer) during the first 12 months oftreatment in patients receiving tofacitinib in clinical trials was 0.6 events per 100patient-years in patients receiving 10 mg twice daily and 0.4 events per 100 patient-years in patients receiving 5 mg twice daily. The most common malignancies reported,including those reported during long-term extension studies, were lung and breastcancer, followed by gastric, colorectal, renal cell, and prostate cancer, lymphoma, andmalignant melanoma.

Studies of longer duration are needed to evaluate the risk of malignancy associatedwith tofacitinib; however, current data suggest that the incidence rates for allmalignancies in patients receiving tofacitinib for the treatment of rheumatoid arthritisare consistent with published estimates in patients with rheumatoid arthritis receivingbiologic or nonbiologic DMARDs.

EBV-associated posttransplant lymphoproliferative disorder was observed in 5 of218 patients (2.3%) receiving tofacitinib compared with 0 of 111 patients receivingcyclosporine in dose-ranging trials in de novo renal transplant recipients; all patientshad received induction therapy with basiliximab, high-dose corticosteroids, andmycophenolate.

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Omeprazole

56:28.36 Proton-pump Inhibitors (AHFS primary)

Omeprazole Magnesium

56:28.36 Proton-pump Inhibitors (AHFS primary)

■ Omeprazole, commonly referred to as an acid- or proton-pump inhibitor, is agastric antisecretory agent.

UsesOmeprazole is used in adults for the short-term treatment of active duodenal and

benign gastric ulcer. Omeprazole also is used in combination with clarithromycin (dualtherapy) or with amoxicillin and clarithromycin (triple therapy) for the treatment ofHelicobacter pylori infection and duodenal ulcer disease in adults. Omeprazole alsohas been used in other multiple-drug regimens (with or without clarithromycin)† forthe treatment of H. pylori infection associated with peptic ulcer disease. Omeprazoleis used in adults and children 1 year of age and older for short-term treatment andsymptomatic relief of gastroesophageal reflux disease (e.g., erosive esophagitis,heartburn) and as maintenance therapy following healing of erosive esophagitis toreduce its recurrence. The drug also is used as self-medication for short-term treatmentand symptomatic relief of frequent heartburn in adults. Omeprazole is used for thelong-term treatment of pathologic GI hypersecretory conditions in adults. Omeprazolealso is used to decrease the risk of upper GI bleeding in critically ill adults.■ Duodenal UlcerAcute Therapy

Omeprazole immediate- and delayed-release capsules, omeprazole immediate-release oral suspension, and omeprazole magnesium delayed-release oral suspensionare used in adults for the short-term treatment of endoscopically or radiographicallyconfirmed active duodenal ulcer. Antacids may be used concomitantly as neededfor pain relief. In controlled studies in patients with endoscopically confirmedduodenal ulcers, reported rates of ulcer healing for omeprazole were substantiallyhigher than those for placebo. In a multicenter, double-blind study in patients withendoscopically confirmed duodenal ulcer, reported rates of ulcer healing for an oralomeprazole dosage of 20 mg each morning or placebo were 41 or 13%, respectively,at 2 weeks and 75 or 27%, respectively, at 4 weeks. Omeprazole also produced greaterreductions in daytime and nocturnal pain and antacid consumption than did placebo,with complete relief of pain in most patients usually occurring within 4 weeks afterinitiation of omeprazole therapy.

Omeprazole appears to be at least as effective as histamine H2-receptor antagonistsfor short-term treatment of active duodenal ulcer. In a multicenter, controlled studyin patients with endoscopically confirmed duodenal ulcers, 42 or 34% of ulcers werehealed following oral administration of omeprazole 20 mg each morning or ranitidine150 mg twice daily, respectively, for 2 weeks and 82 or 63%, respectively, were healedafter 4 weeks of therapy. In another multicenter, controlled study in patients withendoscopically confirmed duodenal ulcers, ulcer healing occurred faster in patients

therapy is associated with a high rate of ulcer recurrence (e.g., 60–100% per year). TheAmerican College of Gastroenterology (ACG), the National Institutes of Health (NIH),and most clinicians currently recommend that all patients with initial or recurrentall patients with initial or recurrentallduodenal or gastric ulcer and documented H. pylori infection receive anti-infectivetherapy for treatment of the infection. Although 3-drug regimens consisting of abismuth salt (e.g., bismuth subsalicylate) and 2 anti-infective agents (e.g., tetracyclineor amoxicillin plus metronidazole) administered for 10–14 days have been effectivein eradicating the infection, resolving associated gastritis, healing peptic ulcer, andpreventing ulcer recurrence in many patients with H. pylori-associated peptic ulcerdisease, current evidence principally from studies in Europe suggests that 1 week ofsuch therapy provides comparable H. pylori eradication rates. Other regimens thatcombine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with abismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, histamineH2-receptor antagonist) also have been used successfully for H. pylori eradication,and the choice of a particular regimen should be based on the rapidly evolving data onoptimal therapy, including consideration of the patient’s prior exposure to anti-infectiveagents, the local prevalence of resistance, patient compliance, and costs of therapy.

Current evidence suggests that inclusion of a proton-pump inhibitor (e.g.,omeprazole, lansoprazole) in anti-H. pylori regimens containing 2 anti-infectivesenhances effectiveness, and limited data suggest that such regimens retain goodefficacy despite imidazole (e.g., metronidazole) resistance. Therefore, the ACG andmany clinicians currently recommend 1 week of therapy with a proton-pump inhibitorand 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole),or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline)concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection.

Therapy with an antisecretory drug and a single anti-infective agent (i.e., “dualtherapy”) also has been used successfully for treatment of H. pylori infection.However, while some studies demonstrate that certain 2-drug anti-H. pylori regimens(e.g., clarithromycin-omeprazole, ranitidine bismuth citrate-omeprazole, amoxicillin-omeprazole) can successfully eradicate H. pylori infection and prevent recurrence ofduodenal ulcer at least in the short term (e.g., at 6 months following completion ofanti-H. pylori therapy), the ACG and some clinicians currently state that anti-H. pyloriregimens consisting of at least 3 drugs (e.g., 2 anti-infective agents plus a proton-pump inhibitor) are recommended because of enhanced H. pylori eradication rates,decreased failures due to resistance, and shorter treatment periods compared withthose apparently required with 2-drug regimens. Additional randomized, controlledstudies comparing various anti-H. pylori regimens are needed to clarify optimumdrug combinations, dosages, and durations of treatment for H. pylori infection. For amore complete discussion of H. pylori infection, including details about the efficacyof various regimens and rationale for drug selection, see Uses: Helicobacter pyloriInfection, in Clarithromycin 8:12.12.92.■ Gastric UlcerAcute Therapy

Omeprazole immediate- and delayed-release capsules, omeprazole immediate-release oral suspension, and omeprazole magnesium delayed-release oral suspensionare used in adults for the short-term treatment and symptomatic relief of active benigngastric ulcer. In controlled studies in patients with endoscopically confirmed gastriculcers, reported rates of ulcer healing with omeprazole therapy were substantiallyhigher than those with placebo. In a multicenter, double-blind study in patients withendoscopically confirmed gastric ulcer, reported rates of ulcer healing with omeprazole20 or 40 mg daily or placebo were 48, 56, or 31%, respectively, at 4 weeks and 75, 83,or 48%, respectively, at 8 weeks. In patients with an ulcer larger than 1 cm in size, the

Page 1 of 11

Omeprazole

56:28.36 Proton-pump Inhibitors (AHFS primary)

Omeprazole Magnesium

56:28.36 Proton-pump Inhibitors (AHFS primary)

■ Omeprazole, commonly referred to as an acid- or proton-pump inhibitor, is agastric antisecretory agent.

UsesOmeprazole is used in adults for the short-term treatment of active duodenal and

benign gastric ulcer. Omeprazole also is used in combination with clarithromycin (dualtherapy) or with amoxicillin and clarithromycin (triple therapy) for the treatment ofHelicobacter pylori infection and duodenal ulcer disease in adults. Omeprazole alsohas been used in other multiple-drug regimens (with or without clarithromycin)† forthe treatment of H. pylori infection associated with peptic ulcer disease. Omeprazoleis used in adults and children 1 year of age and older for short-term treatment andsymptomatic relief of gastroesophageal reflux disease (e.g., erosive esophagitis,heartburn) and as maintenance therapy following healing of erosive esophagitis toreduce its recurrence. The drug also is used as self-medication for short-term treatmentand symptomatic relief of frequent heartburn in adults. Omeprazole is used for thelong-term treatment of pathologic GI hypersecretory conditions in adults. Omeprazolealso is used to decrease the risk of upper GI bleeding in critically ill adults.■ Duodenal UlcerAcute Therapy

Omeprazole immediate- and delayed-release capsules, omeprazole immediate-release oral suspension, and omeprazole magnesium delayed-release oral suspensionare used in adults for the short-term treatment of endoscopically or radiographicallyconfirmed active duodenal ulcer. Antacids may be used concomitantly as neededfor pain relief. In controlled studies in patients with endoscopically confirmedduodenal ulcers, reported rates of ulcer healing for omeprazole were substantiallyhigher than those for placebo. In a multicenter, double-blind study in patients withendoscopically confirmed duodenal ulcer, reported rates of ulcer healing for an oralomeprazole dosage of 20 mg each morning or placebo were 41 or 13%, respectively,at 2 weeks and 75 or 27%, respectively, at 4 weeks. Omeprazole also produced greaterreductions in daytime and nocturnal pain and antacid consumption than did placebo,with complete relief of pain in most patients usually occurring within 4 weeks afterinitiation of omeprazole therapy.

Omeprazole appears to be at least as effective as histamine H2-receptor antagonistsfor short-term treatment of active duodenal ulcer. In a multicenter, controlled studyin patients with endoscopically confirmed duodenal ulcers, 42 or 34% of ulcers werehealed following oral administration of omeprazole 20 mg each morning or ranitidine150 mg twice daily, respectively, for 2 weeks and 82 or 63%, respectively, were healedafter 4 weeks of therapy. In another multicenter, controlled study in patients withendoscopically confirmed duodenal ulcers, ulcer healing occurred faster in patientsgiven omeprazole 20 or 40 mg daily compared with patients given ranitidine 150 mgtwice daily. Ulcer healing rates averaged 83 or 53% at 2 weeks, 97–100 or 82% at 4weeks, and 100 or 94% at 8 weeks with the omeprazole regimens or ranitidine 150 mgtwice daily, respectively. In several studies, ulcer healing was less likely in patientswho were smokers and in those with large ulcers than in other patients.

Most patients with duodenal ulcer respond to omeprazole therapy during the initial4-week course of therapy; an additional 4 weeks of therapy may contribute to healingin some patients.

Omeprazole delayed-release capsules and omeprazole magnesium delayed-releaseoral suspension are used in combination with clarithromycin and amoxicillin (tripletherapy) for the treatment of H. pylori infection and duodenal ulcer disease in adults.Omeprazole delayed-release capsules and omeprazole magnesium delayed-releaseoral suspension also are used in combination with clarithromycin (dual therapy) inadults for the treatment of H. pylori infection and duodenal ulcer disease. Omeprazolealso has been used in other multiple-drug regimens† for the treatment of H. pyloriinfection associated with peptic ulcer disease. Current epidemiologic and clinicalevidence supports a strong association between gastric infection with H. pylori andthe pathogenesis of duodenal and gastric ulcers; long-term H. pylori infection also hasbeen implicated as a risk factor for gastric cancer. For additional information on theassociation of this infection with these and other GI conditions, see Helicobacter pyloriInfection, under Uses, in Clarithromycin 8:12.12.92. Conventional antiulcer therapywith histamine H2-receptor antagonists, proton-pump inhibitors, sucralfate, and/orantacids heals ulcers but generally is ineffective in eradicating H. pylori, and such

therapy is associated with a high rate of ulcer recurrence (e.g., 60–100% per year). TheAmerican College of Gastroenterology (ACG), the National Institutes of Health (NIH),and most clinicians currently recommend that all patients with initial or recurrentduodenal or gastric ulcer and documented H. pylori infection receive anti-infectivetherapy for treatment of the infection. Although 3-drug regimens consisting of abismuth salt (e.g., bismuth subsalicylate) and 2 anti-infective agents (e.g., tetracyclineor amoxicillin plus metronidazole) administered for 10–14 days have been effectivein eradicating the infection, resolving associated gastritis, healing peptic ulcer, andpreventing ulcer recurrence in many patients with H. pylori-associated peptic ulcerdisease, current evidence principally from studies in Europe suggests that 1 week ofsuch therapy provides comparable H. pylori eradication rates. Other regimens thatcombine one or more anti-infective agents (e.g., clarithromycin, amoxicillin) with abismuth salt and/or an antisecretory agent (e.g., omeprazole, lansoprazole, histamineH2-receptor antagonist) also have been used successfully for H. pylori eradication,and the choice of a particular regimen should be based on the rapidly evolving data onoptimal therapy, including consideration of the patient’s prior exposure to anti-infectiveagents, the local prevalence of resistance, patient compliance, and costs of therapy.

Current evidence suggests that inclusion of a proton-pump inhibitor (e.g.,omeprazole, lansoprazole) in anti-H. pylori regimens containing 2 anti-infectivesenhances effectiveness, and limited data suggest that such regimens retain goodefficacy despite imidazole (e.g., metronidazole) resistance. Therefore, the ACG andmany clinicians currently recommend 1 week of therapy with a proton-pump inhibitorand 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole),or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline)concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection.

Therapy with an antisecretory drug and a single anti-infective agent (i.e., “dualtherapy”) also has been used successfully for treatment of H. pylori infection.However, while some studies demonstrate that certain 2-drug anti-H. pylori regimens(e.g., clarithromycin-omeprazole, ranitidine bismuth citrate-omeprazole, amoxicillin-omeprazole) can successfully eradicate H. pylori infection and prevent recurrence ofduodenal ulcer at least in the short term (e.g., at 6 months following completion ofanti-H. pylori therapy), the ACG and some clinicians currently state that anti-H. pyloriregimens consisting of at least 3 drugs (e.g., 2 anti-infective agents plus a proton-pump inhibitor) are recommended because of enhanced H. pylori eradication rates,decreased failures due to resistance, and shorter treatment periods compared withthose apparently required with 2-drug regimens. Additional randomized, controlledstudies comparing various anti-H. pylori regimens are needed to clarify optimumdrug combinations, dosages, and durations of treatment for H. pylori infection. For amore complete discussion of H. pylori infection, including details about the efficacyof various regimens and rationale for drug selection, see Uses: Helicobacter pyloriInfection, in Clarithromycin 8:12.12.92.■ Gastric UlcerAcute Therapy

Omeprazole immediate- and delayed-release capsules, omeprazole immediate-release oral suspension, and omeprazole magnesium delayed-release oral suspensionare used in adults for the short-term treatment and symptomatic relief of active benigngastric ulcer. In controlled studies in patients with endoscopically confirmed gastriculcers, reported rates of ulcer healing with omeprazole therapy were substantiallyhigher than those with placebo. In a multicenter, double-blind study in patients withendoscopically confirmed gastric ulcer, reported rates of ulcer healing with omeprazole20 or 40 mg daily or placebo were 48, 56, or 31%, respectively, at 4 weeks and 75, 83,or 48%, respectively, at 8 weeks. In patients with an ulcer larger than 1 cm in size, thepercentage of patients with healed ulcers at 8 weeks was greater with the 40-mg dosagethan with the 20-mg dosage of omeprazole. Otherwise, for patients with smaller ulcers,no difference in ulcer healing rates between the 40- and 20-mg dosages was observed.

In a multicenter, comparative study in patients with endoscopically confirmedgastric ulcer, ulcer healing occurred at 4 weeks in 64 or 78% of patients receivingomeprazole 20 or 40 mg daily, respectively, compared with 56% of those receivingranitidine 150 mg twice daily; at 8 weeks, 82, 91, or 78% of patients receivingomeprazole 20 mg daily, omeprazole 40 mg daily, or ranitidine 150 mg twice daily,respectively, had healed ulcers.■ Crohn’s Disease-associated Ulcers

Although evidence currently is limited, proton-pump inhibitors have been usedfor gastric acid-suppressive therapy as an adjunct in the symptomatic treatment ofupper GI Crohn’s disease†, including esophageal, gastroduodenal, and jejunoilealdisease. The drugs have been used for symptomatic relief of upper GI symptoms and topromote healing of Crohn’s disease-associated peptic ulcer disease. Most evidence ofefficacy to date has been from case studies in patients with Crohn’s-associated pepticulcer disease unresponsive to other therapies (e.g., histamine H2-receptor antagonists,cytoprotective agents, antacids, and/or sucralfate). Omeprazole (20 or 40 mg daily)was associated with resolution of symptoms and ulcer healing within about 2 and 4weeks, respectively, in some patients, while others required several months of acid-suppressive therapy. Subsequent symptomatic relief may be maintained with prolongedacid-suppressive therapy with a proton-pump inhibitor or H2-receptor antagonist, withor without an immunosuppressive agent (e.g., azathioprine). Adjunctive inhibition

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information, when the package insert is not adequate for my needs.” Lisa Vivero, Pharm.D., Drug Information Pharmacist, Consultant

AHFS DI: Delivering 56 Years of Trusted Intelligence to our Partners and Colleagues in the Pharmacy CommunityOrder today to have the most leading-edge information immediately

available for the best in patient care.

Plus, renew or order now and get access to critical password-protected

updates only available to new subscribers.

AHFS Drug Information is a collection of drug monographs on

virtually every single-drug entity available in the United States.

Visit this link to view a sample monograph:{ or scan this page with your A/R app! }www.ahfsdruginformation.com/docs/ahfsdi_monograph.pdf

Information within each drug monograph is divided into the

following sections and subsections:

Monograph Title and SynonymsREMSIntroductory DescriptionUsesDosage and Administration

Reconstitution and Admin.AdministrationDosageDosage in Renal (and Hepatic) Impairment

CautionsAdverse EffectsPrecautions and ContraindicationsPediatric PrecautionsGeriatric PrecautionsMutagenicity and CarcinogenicityPregnancy, Fertility, and Lactation

Drug InteractionsLaboratory Test Interferences

Acute ToxicityPathogenesisManifestationsTreatment

Chronic ToxicityPathogenesisManifestationsTreatment

PharmacologyMechanism of Action (for anti-infectives)Spectrum (for anti-infectives)Resistance (for anti-infectives)Pharmacokinetics

AbsorptionDistributionElimination

Chemistry and StabilityChemistryStability

Preparations

R

Download the FREE “Layar” app from your app store to directly access all of this:

� Link to order or renew your subscription

� Online purchasing options

� Licensing information

� A sample monograph

� Preface to the new 2014 edition to see what’s new

� Subscribers-only features

� Our new AHFS DI Facebook page, www.facebook.com/ahfsdruginformation

� Our new Twitter feed @AHFSDI

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Download the FREE “Layar” app from your app store to directly access all of this:h

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TO ORDER THE 2014 EDITION OF AHFS DI, complete and return the form in the enclosed envelope, or call 866-279-0681 (U.S. and Canada), or 001-301-664-8700 (international). Order online at: www.ahfsdruginformation.com.

TO ORDER THE 2014 EDITION OF AHFS DI, complete and return the form in the enclosed envelope, or call 866-279-0681 (U.S. and Canada), or 001-301-664-8700 (international). Order online at: www.ahfsdruginformation.com.

New for 2014: Like us on Facebook and follow us on Twitter!

{ www.facebook.com/ahfsdruginformation }

{ @AHFSDI }

Become a Drug Information fan. Look for discounts and special

offers on new products, and connect to your peers.

Online access is quick and easy!To set up your online account, contact one of our partners today. AHFS is available to purchase as an online solution through several

trusted partners. Follow the link below to view the different options

and pricing that our partners offer, to determine which best suit your

needs. Many offer free trials as a way to try out the product.

{ www.ahfsdruginformation.com/product-ahfs-di.aspx }

HERE’S HOW TO ORDER THE NEW 2014 EDITION: 1. Return the order form in the enclosed envelope,

2. Call 866-279-0681 (U.S. and Canada), or 001-301-664-8700 (international)., OR

3. Order online at: www.ahfsdruginformation.com.

Buy both and save 10%.

Remember that AHFS is available as a package with the Handbook on Injectable Drugs.

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