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OMEPRAZOLE

Introduction
C17H19N3O3S
Omeprazole, commonly referred to as an acid- or proton-pump inhibitor,1, 2, 3, 4, 5, 8, 132 is a
gastric antisecretory agent.1, 2, 3, 4, 5
Uses
Omeprazole delayed-release capsules and oral suspension are used in adults for the short-term
treatment of active duodenal and benign gastric ulcer.1, 2, 3, 4, 8, 98, 207, 208 Omeprazole delayedrelease capsules also are used in combination with clarithromycin (dual therapy) or with
amoxicillin and clarithromycin (triple therapy) for the treatment of Helicobacter pylori infection
and duodenal ulcer disease in adults.1, 138 Omeprazole also has been used in other multiple-drug
regimens (with or without clarithromycin)# for the treatment of H. pylori infection associated
with peptic ulcer disease.29, 32, 67, 68, 69, 70, 75, 78, 82, 138 Omeprazole delayed-release capsules are
used in adults and children 2 years of age and older, and the oral suspension is used in adults for
short-term treatment and symptomatic relief of gastroesophageal reflux disease (e.g., erosive
esophagitis, heartburn), 1, 2, 3, 4, 5, 97, 98, 207, 208 and as maintenance therapy following healing of
erosive esophagitis to reduce its recurrence.1, 92, 93, 94, 95, 96, 97, 98, 207, 208 Omeprazole magnesium
delayed-release capsules are used as self-medication for short-term treatment and symptomatic
relief of frequent heartburn in adults.187, 188, 189 Omeprazole delayed-release capsules are used for
the long-term treatment of pathologic GI hypersecretory conditions in adults.1, 2, 3, 4, 5, 8, 13, 98
Omeprazole oral suspension is used to decrease the risk of upper GI bleeding in critically ill
adults.207, 211
Duodenal Ulcer
Acute Therapy
Omeprazole delayed-release capsules and oral suspension are used in adults for the short-term
treatment of endoscopically or radiographically confirmed active duodenal ulcer.1, 2, 3, 4, 8, 207, 208
Antacids may be used concomitantly as needed for pain relief.1, 6, 207, 208 In controlled studies in
patients with endoscopically confirmed duodenal ulcers, reported rates of ulcer healing for
omeprazole were substantially higher than those for placebo.1, 2, 3, 4, 6, 8, 207 In a multicenter,
double-blind study in patients with endoscopically confirmed duodenal ulcer, reported rates of
ulcer healing for an oral omeprazole dosage of 20 mg each morning or placebo were 41 or 13%,
respectively, at 2 weeks and 75 or 27%, respectively, at 4 weeks.1, 2, 3, 6, 207 Omeprazole also
produced greater reductions in daytime and nocturnal pain and antacid consumption than did
placebo, with complete relief of pain in most patients usually occurring within 4 weeks after
initiation of omeprazole therapy.1, 6, 207
Omeprazole appears to be at least as effective as H2-receptor antagonists for short-term treatment
of active duodenal ulcer.1, 2, 3, 4, 8, 207 In a multicenter, controlled study in patients with
endoscopically confirmed duodenal ulcers, 42 or 34% of ulcers were healed following oral
administration of omeprazole 20 mg each morning or ranitidine 150 mg twice daily, respectively,
for 2 weeks and 82 or 63%, respectively, were healed after 4 weeks of therapy.1, 3, 8, 10, 207 In
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another multicenter, controlled study in patients with endoscopically confirmed duodenal ulcers,
ulcer healing occurred faster in patients given omeprazole 20 or 40 mg daily compared with
patients given ranitidine 150 mg twice daily.1, 9, 207 Ulcer healing rates averaged 83 or 53% at 2
weeks, 97-100 or 82% at 4 weeks, and 100 or 94% at 8 weeks with the omeprazole regimens or
ranitidine 150 mg twice daily, respectively.1, 3, 8, 9 In several studies, ulcer healing was less likely
in patients who were smokers and in those with large ulcers than in other patients.8, 207
Most patients with duodenal ulcer respond to omeprazole therapy during the initial 4-week
course of therapy; an additional 4 weeks of therapy may contribute to healing in some patients.1
Omeprazole delayed-release capsules are used in combination with clarithromycin and
amoxicillin (triple therapy) for the treatment of H. pylori infection and duodenal ulcer disease in
adults.1, 138 Omeprazole also is used in combination with clarithromycin (dual therapy) in adults
for the treatment of H. pylori infection and duodenal ulcer disease.1, 138 Omeprazole also has
been used in other multiple-drug regimens# for the treatment of H. pylori infection associated
with peptic ulcer disease.27, 28, 29, 37, 38, 39, 61, 62, 66, 67, 75, 76, 77, 78, 79, 81, 82, 106, 108, 110, 111, 112, 113, 115,
138
Current epidemiologic and clinical evidence supports a strong association between gastric
infection with H. pylori and the pathogenesis of duodenal and gastric ulcers;27, 28, 31, 34, 64, 66, 71,
108, 110, 111, 112, 113, 117, 118, 119, 120, 121, 122
long-term H. pylori infection also has been implicated as a
28, 50, 51, 52, 53, 54, 55, 56, 57, 58, 66, 108, 110, 120
risk factor for gastric cancer.
For additional information
on the association of this infection with these and other GI conditions, see Helicobacter pylori
Infection, under Uses, in Clarithromycin 8:12.12.92. Conventional antiulcer therapy with H2receptor antagonists, proton-pump inhibitors, sucralfate, and/or antacids 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).27, 34, 108, 110, 111, 112, 122 The American College of
Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently
recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H.
pylori infection receive anti-infective therapy for treatment of the infection.80, 108, 111, 112, 113, 138
Although 3-drug regimens consisting of a bismuth salt (e.g., bismuth subsalicylate) and 2 antiinfective agents (e.g., tetracycline or amoxicillin plus metronidazole) administered for 10-14
days have been effective in eradicating the infection, resolving associated gastritis, healing peptic
ulcer, and preventing ulcer recurrence in many patients with H. pylori-associated peptic ulcer
disease,27, 28, 29, 31, 32, 33, 43, 59, 60, 61, 63, 64, 66, 71, 72, 75, 108, 110, 111, 112, 113, 114, 116, 121, 129, 138 current
evidence principally from studies in Europe suggests that 1 week of such therapy provides
comparable H. pylori eradication rates.108, 112, 113 Other regimens that combine one or more antiinfective agents (e.g., clarithromycin, amoxicillin) with a bismuth salt and/or an antisecretory
agent (e.g., omeprazole, lansoprazole, H2-receptor antagonist) also have been used successfully
for H. pylori eradication,27, 28, 29, 37, 38, 39, 61, 62, 66, 67, 75, 76, 77, 78, 79, 81, 82, 106, 108, 110, 111, 112, 113, 115,
133, 134, 135, 136, 137, 138
and the choice of a particular regimen should be based on the rapidly
evolving data on optimal therapy, including consideration of the patient's prior exposure to antiinfective agents, the local prevalence of resistance, patient compliance, and costs of therapy.80,
108, 109, 110, 112, 129

Current evidence suggests that inclusion of a proton-pump inhibitor (e.g., omeprazole,


lansoprazole) in anti-H. pylori regimens containing 2 anti-infectives enhances effectiveness, and
limited data suggest that such regimens retain good efficacy despite imidazole (e.g.,
metronidazole) resistance.108, 112, 133, 138 Therefore, the ACG and many clinicians108, 114, 115, 138
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currently recommend 1 week of therapy with a proton-pump inhibitor and 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.108, 112, 115, 138
Therapy with an antisecretory drug and a single anti-infective agent (i.e., "dual therapy") also has
been used successfully for treatment of H. pylori infection.37, 38, 39, 40, 41, 62, 63, 67, 106, 107, 110, 112,
127, 133, 134, 138
However, while some studies demonstrate that certain 2-drug anti-H. pylori
regimens (e.g., clarithromycin-omeprazole, ranitidine bismuth citrate-omeprazole, amoxicillinomeprazole) can successfully eradicate H. pylori infection and prevent recurrence of duodenal
ulcer at least in the short term (e.g., at 6 months following completion of anti-H. pylori
therapy),105, 106, 107, 112, 113, 114, 138 the ACG and some clinicians currently state that anti-H. pylori
regimens 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 with those apparently required with 2-drug
regimens.27, 32, 106, 108, 110, 114, 133, 138 Additional randomized, controlled studies comparing various
anti-H. pylori regimens are needed to clarify optimum drug combinations, dosages, and durations
of treatment for H. pylori infection.108, 109, 115, 129, 133, 138 For a more complete discussion of H.
pylori infection, including details about the efficacy of various regimens and rationale for drug
selection, see Uses: Helicobacter pylori Infection, in Clarithromycin 8:12.12.92.
Gastric Ulcer
Acute Therapy
Omeprazole delayed-release capsules and oral suspension are used in adults for the short-term
treatment and symptomatic relief of active benign gastric ulcer.1, 207, 208 In controlled studies in
patients with endoscopically confirmed gastric ulcers, reported rates of ulcer healing with
omeprazole therapy were substantially higher than those with placebo.1, 207 In a multicenter,
double-blind study in patients with endoscopically confirmed gastric ulcer, reported rates of
ulcer healing with omeprazole 20 or 40 mg daily or placebo were 48, 56, or 31%, respectively, at
4 weeks and 75, 83, or 48%, respectively, at 8 weeks.1, 207 In patients with an ulcer larger than 1
cm in size, the percentage of patients with healed ulcers at 8 weeks was greater with the 40-mg
dosage than with the 20-mg dosage of omeprazole.1, 207 Otherwise, for patients with smaller
ulcers, no difference in ulcer healing rates between the 40- and 20-mg dosages was observed.1,
207

In a multicenter, comparative study in patients with endoscopically confirmed gastric ulcer, ulcer
healing occurred at 4 weeks in 64 or 78% of patients receiving omeprazole 20 or 40 mg daily,
respectively, compared with 56% of those receiving ranitidine 150 mg twice daily; at 8 weeks,
82, 91, or 78% of patients receiving omeprazole 20 mg daily, omeprazole 40 mg daily, or
ranitidine 150 mg twice daily, respectively, had healed ulcers.1
Crohn's Disease-associated Ulcers
Although evidence currently is limited, proton-pump inhibitors have been used for gastric acidsuppressive therapy as an adjunct in the symptomatic treatment of upper GI Crohn's disease#,
including esophageal, gastroduodenal, and jejunoileal disease.190, 191, 192, 194, 195, 196 The drugs
have been used for symptomatic relief of upper GI symptoms and to promote healing of Crohn's
disease-associated peptic ulcer disease.190, 191, 192, 194, 195, 196 Most evidence of efficacy to date has
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been from case studies in patients with Crohn's-associated peptic ulcer disease unresponsive to
other therapies (e.g., H2-receptor antagonists, cytoprotective agents, antacids, and/or
sucralfate).191, 192 Omeprazole (20 or 40 mg daily) was associated with resolution of symptoms
and ulcer healing within about 2 and 4 weeks,191 respectively, in some patients, while others
required several months of acid-suppressive therapy.192 Subsequent symptomatic relief may be
maintained with prolonged acid-suppressive therapy with a proton-pump inhibitor or H2-receptor
antagonist, with or without an immunosuppressive agent (e.g., azathioprine).191, 192 Adjunctive
inhibition of gastric acid secretion is likely to be more effective in promoting ulcer healing in
Crohn's disease than corticosteroid therapy.191 Pending accumulation of more definitive
evidence, some experts and clinicians state that therapy with a proton-pump inhibitor may be a
useful adjunct to provide symptomatic relief and promote ulcer healing in patients with upper GI
Crohn's disease.190, 193
(For further information on the the management of Crohn's Disease, see Uses: Crohn's Disease,
in Mesalamine 56:36.)
Gastroesophageal Reflux
Omeprazole delayed-release capsules and oral suspension are used in adults and delayed-release
capsules are used in children 2 years of age and older for the short-term treatment and
symptomatic relief of gastroesophageal reflux disease (GERD) (e.g., erosive esophagitis,
heartburn)1, 2, 3, 4, 5, 97, 98, 207, 208 and as maintenance therapy following healing of erosive
esophagitis to prevent its recurrence.1, 92, 93, 94, 95, 96, 97, 98, 207, 208 Safety and efficacy of
omeprazole oral suspension have not been established in pediatric patients.207 Omeprazole
magnesium delayed-release capsules are used in adults as self-medication for the short-term
treatment and symptomatic relief of frequent heartburn.187, 188, 189
GERD is considered to be a chronic disease, and many patients with GERD require long-term,
even lifelong, treatment.143 Typical GERD symptoms include heartburn and/or regurgitation,
often occurring after meals, especially large and/or fatty meals.143 The symptoms often are
aggravated by recumbency or bending, and are relieved by antacids.143 GERD symptoms
generally are controlled by appropriate medical therapy.143 Suppression of gastric acid secretion
is considered by the ACG to be the mainstay of treatment for GERD, and a proton-pump
inhibitor or histamine H2-receptor antagonist is used to achieve acid suppression, control
symptoms, and prevent complications of the disease.143 The ACG states that proton-pump
inhibitors are more effective than histamine H2-receptor antagonists for acute therapy of GERD
and also are appropriate as maintenance therapy in many patients with the disease.143 Lifestyle
modifications (e.g., elevation of the head of the bed, decreased dietary fat intake, smoking
cessation, avoidance of recumbency for 3 hours after a meal, avoidance of foods that increase
reflux, weight loss) should be initiated and continued throughout the course of treatment.143
Acute Therapy
Omeprazole delayed-release capsules are used in adults and children 2 years of age and older,
and the oral suspension is used in adults for the short-term (4-8 weeks) treatment of
endoscopically diagnosed erosive esophagitis in patients with GERD.1, 2, 3, 4, 5, 8, 92, 93, 94, 95, 96, 97,
98, 207, 208
Omeprazole delayed-release capsules are used in adults and children 2 years of age and
older, and the oral suspension is used in adults for the short-term (4-8 weeks) treatment of
symptomatic GERD (e.g., heartburn).1, 5, 97 Potential benefits of omeprazole in gastroesophageal
4

reflux and esophagitis are thought to result principally from reduced acidity of gastric contents
induced by the drug and resultant reduced irritation of esophageal mucosa; the drug can
effectively relieve symptoms of esophagitis (e.g., heartburn) and promote healing of ulcerative
and erosive lesions.1, 2, 3, 4, 5, 8, 12, 207, 208
Drug Selection Considerations
The ACG states that proton-pump inhibitors are more effective (i.e., provide more frequent and
more rapid symptomatic relief and healing of esophagitis) than histamine H2-receptor antagonists
in the treatment of GERD.143 Although higher doses and more frequent administration of
histamine H2-receptor antagonists appear to increase their efficacy, such dosages are less
effective and more expensive than proton-pump inhibitor therapy.143, 144, 145, 146 In addition, the
ACG states that proton-pump inhibitors provide greater control of acid reflux than do prokinetic
agents (e.g., cisapride [no longer commercially available in the US], metoclopramide) without
the risk of severe adverse effects associated with these agents.143 Correction of esophageal and
gastric motility defects that cause GERD might theoretically control the disease and make
suppression of normal gastric acid secretion unnecessary,143 and prokinetic agents have been
used in the treatment of GERD.143 However, cisapride was withdrawn from the US market
because of its association with serious cardiac arrhythmias and death (see Cisapride 56:32),143,
147, 148, 148, 149, 150, 151, 152, 153, 154
and metoclopramide frequently is associated with adverse CNS
effects (e.g., restlessness, drowsiness, fatigue, lassitude).143, 155, 162, 166, 168, 169 The ACG states
that the frequent occurrence of adverse CNS effects has appropriately decreased regular use of
metoclopramide for treatment of GERD.143, 162 Cisapride or metoclopramide therapy appears to
provide symptomatic relief and esophageal healing as effectively as a standard dosage of a
histamine H2-receptor antagonist,143, 180, 181, 182 and improved efficacy has been reported when a
prokinetic agent has been used in combination with a histamine H2-receptor antagonist.143, 183, 184
Bethanechol, a cholinergic drug that increases GI motility, may increase lower esophageal
sphincter pressure to a small degree, but the ACG states that the drug has limited efficacy in the
treatment of GERD.143
Considerable controversy exists about whether a proton-pump inhibitor or histamine H2-receptor
antagonist should be used for initial therapy of GERD.143 A proton-pump inhibitor administered
once or twice daily has been used initially in "step-down" regimens that decrease dosage and
may change the drug used to the least potent acid-suppression regimen that provides symptom
control.143 Alternatively, therapy has been initiated with a histamine H2-receptor antagonist at
low or full dosage in "step-up" regimens that increase intensity of therapy to that which controls
symptoms.143 However, neither type of regimen has been proven superior, and the ACG states
that the choice of an initial regimen is best left to the individual clinician in consultation with the
patient.143, 185, 186
The ACG states that a histamine H2-receptor antagonist administered daily in divided doses is
effective in many patients with less severe GERD, and over-the-counter (OTC) antacids and
histamine H2-receptor antagonists are appropriate for self-medication as initial therapy in such
individuals.143 A histamine H2-receptor antagonist is particularly useful when taken before
certain activities (e.g., heavy meal, exercise) that may result in acid reflux symptoms in some
patients.143
Other Considerations
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The ACG states that initial empiric therapy including suppression of gastric acid secretion and
lifestyle modification is appropriate for patients with typical symptoms of uncomplicated GERD,
and a diagnosis of GERD is reasonably assumed in those who respond to such therapy.143
Diagnostic testing (e.g., endoscopy, endoscopic biopsy, ambulatory pH testing, esophageal
manometry) may be indicated when empiric drug therapy is unsuccessful, continuous medical
therapy is required for symptomatic relief, chronic symptoms occur in patients at risk for
esophageal metaplasia (e.g., Barrett's epithelium), or manifestations suggestive of complicated
disease (e.g., dysphagia, bleeding, weight loss, choking [acid causing cough, shortness of breath,
or hoarseness], chest pain) occur.143 In patients with symptoms refractory to empiric drug
therapy, the diagnosis of GERD should be carefully confirmed with diagnostic testing before
chronic, high-dose acid-suppression therapy or antireflux surgery is undertaken.143 Higher
dosage and a longer therapeutic trial of a gastric antisecretory agent may be required in patients
with atypical or extraesophageal symptoms (e.g., chronic chest pain, cough, hoarseness, asthma,
dental erosions).143
Clinical Trials
In a controlled study in patients with manifestations of GERD (e.g., heartburn) and the absence
of erosive esophageal lesions, symptomatic improvement with omeprazole was better than that
with placebo.1, 207 Complete resolution of heartburn was reported in 56, 36, or 14% of patients
with endoscopically confirmed GERD and in 46, 31, or 13% of all enrolled patients after up to 4
weeks of therapy with omeprazole 20 mg daily, omeprazole 10 mg daily, or placebo,
respectively.1, 207
In an uncontrolled, open-label study of 113 pediatric patients 2 -16 years of age with a history of
symptoms suggestive of nonerosive GERD, patients received an omeprazole dosage of 10 or 20
mg once daily (based on body weight) either as an intact capsule or as an open capsule in
applesauce.1, 198 The number and intensity of either pain-related symptoms or
vomiting/regurgitation episodes was successfully reduced in 60 or 59% of those receiving
omeprazole 10 or 20 mg, respectively.1, 198
In controlled studies in patients with endoscopically diagnosed erosive esophagitis and
symptoms of GERD, reported rates of healing with omeprazole were higher than those with
placebo or an H2-receptor antagonist.1, 2, 4, 8, 12, 207 Healing rates from a controlled study were 39,
45, or 7% at 4 weeks and 74, 75, or 14% at 8 weeks for omeprazole 20 mg daily, 40 mg daily, or
placebo, respectively.1, 3, 12, 207 In controlled studies in patients with esophagitis, reported rates of
healing were 57-74 or 27-43% at 4 weeks and 78-87 or 28-56% at 8 weeks in patients given
omeprazole or ranitidine, respectively.2, 8, 207 Patients receiving omeprazole reported faster relief
of daytime and nocturnal heartburn than those receiving placebo1, 2, 12, 207 or an H2-receptor
antagonist.1, 2, 8, 207 Omeprazole also has been shown to be effective in promoting healing and
providing symptomatic relief in a substantial proportion of patients who failed to respond to an
adequate course of relatively high dosages of an H2-receptor antagonist.2, 97, 98
In an uncontrolled, open-label dose-titration study in 57 pediatric patients aged 1-16 years of age
with erosive esophagitis, omeprazole dosages of 0.7-3.5 mg/kg daily were required to promote
healing.1, 197, 198 Dosages were initiated at 0.7 mg/kg daily and if therapeutic goals
(intraesophageal pH below 4 for less than 6% of a 24-hour period) were not achieved after 5-14
days of treatment, the dosage was increased to 1.4 mg/kg daily.1, 197, 198 Based on additional
6

measurements of intraesophageal pH and/or presence of pathologic acid reflux, the dosages were
increased up to a maximum dosage of 3.5 mg/kg or 80 mg daily. 1, 197, 198 After titration of
omeprazole dosage, patients remained on treatment for 3 months (healing phase); patients with
persistent erosive esophagitis after 3 months received a discretionary dosage increase and
treatment for an additional 3 months.1, 197, 198 Erosive esophagitis was healed in 90% of children
completing the first course of treatment in the healing phase of the study;1, 197, 198 5% received a
second treatment course. 197, 198 Healing occurred in 44% of the patients receiving omeprazole
0.7 mg/kg daily, and an additional 28% were healed with 1.4 mg/kg daily.1, 197, 198 After 3
months of treatment, 33% of the children had no overall symptoms, 57% had mild reflux
symptoms, and 40% had less frequent regurgitation or vomiting.1, 198
Most patients with GERD respond to omeprazole therapy during an initial 8-week course of
therapy; however, an additional 4 weeks of therapy may contribute to healing and symptomatic
improvement in some patients.1, 207 Short-term omeprazole therapy for the treatment of GERD
will not prevent recurrence following discontinuance of the drug.2, 4, 8, 207, 208 If symptomatic
GERD or erosive esophagitis recur, the manufacturers state that additional 4- to 8-week courses
of omeprazole may be given.1, 207 However, the ACG states that chronic therapy with a protonpump inhibitor is appropriate in many patients with GERD.143
Maintenance Therapy
Omeprazole delayed-release capsules are used in adults and children 2 years of age and older,
and the oral suspension is used in adults as maintenance therapy following healing of erosive
esophagitis to reduce recurrence of the disease.1, 92, 93, 94, 95, 96, 207, 208 In a multicenter, doubleblind study, endoscopically documented remission of esophagitis was maintained at 6 months in
70, 34, or 11% of patients receiving omeprazole 20 mg daily, 20 mg on 3 consecutive days each
week, or placebo, respectively.1, 207 In another multicenter, double-blind study in patients with
endoscopically confirmed healed esophagitis, endoscopic remission of esophagitis was
maintained at 12 months in 77, 58, or 46% of patients receiving omeprazole 20 mg daily, 10 mg
daily, or ranitidine 150 mg twice daily, respectively.1, 92, 207 However, patients with initial grade
3 or 4 erosive esophagitis required 20 mg of omeprazole daily for maintenance of healing.1, 92, 207
In an uncontrolled, open-label study in 46 pediatric patients, maintenance dosages were half the
dosages that were required for promotion of healing in 54% of the children studied.1, 198 The
remaining patients required a dosage increase (0.7 to a maximum of 2.8 mg/kg daily) for all or
part of the maintenance period.1, 198 There was no relapse of erosive esophagitis in 41% of the
patients, and no symptoms occurred in 63% of the pediatric patients receiving omeprazole
maintenance therapy.1, 198
Because GERD is a chronic condition, the ACG states that continuous therapy to control
symptoms and prevent complications of the disease is appropriate, and chronic, even lifelong,
use of a proton-pump inhibitor is effective and appropriate as maintenance therapy in many
patients with GERD.143 Although neither medical nor surgical therapy of GERD appears to result
in regression of Barrett's epithelium in the esophagus,143, 145, 176 chronic use of a proton-pump
inhibitor at full dosage decreases the recurrence of esophageal strictures, increases the interval
between symptomatic relapses, and may improve esophageal motility.143, 173, 174, 179 In a doubleblind, controlled study, antisecretory therapy had no clinically important effect on Barrett's
mucosa in 106 patients receiving omeprazole (40 mg twice daily for 12 months, followed by 20
7

mg twice daily for 12 months) or ranitidine (300 mg twice daily for 24 months).1 Although
neosquamous epithelium developed during antisecretory therapy, complete elimination of
Barrett's mucosa was not achieved.1
The frequent marked improvement in symptoms associated with full dosage of a proton-pump
inhibitor generally is followed by rapid recurrence of symptoms once the drug is discontinued,143,
177
and reduced-dosage regimens (e.g., every other day, "weekend" dosage) have not been shown
to be consistently effective for maintenance therapy.143, 171, 172 In addition, many patients initially
responding to proton-pump inhibitors experience symptomatic relapse and failure of esophageal
healing when switched subsequently to a histamine H2-receptor antagonist or prokinetic agent
(e.g., cisapride, metoclopramide).143, 178 Furthermore, prokinetic agents have been associated
with severe adverse effects.143 Cisapride has been withdrawn from the US market because of its
association with serious cardiac arrhythmias and death (see Cisapride 56:32),143, 147, 148, 149, 150,
151, 152, 153, 154
and metoclopramide frequently is associated with CNS adverse effects (e.g.,
restlessness, drowsiness, fatigue, lassitude)143, 155, 162, 166, 168, 169 and may cause irreversible
tardive dyskinesia with prolonged use.143, 155, 156, 157, 159, 160, 161, 162, 170 Once-daily administration
of a histamine H2-receptor antagonist at full dosage is not considered to be appropriate therapy
for GERD.143 Although antacids and lifestyle modifications may provide long-term symptomatic
control in up to 20% of patients with GERD,143 frequent symptomatic relapses may occur despite
appropriate therapy in up to 50% of patients with chronic gastroesophageal reflux.143
Self-Medication
Omeprazole magnesium delayed-release capsules are used in adults 18 years of age or older as
self-medication for short-term (14 days) treatment and symptomatic relief of frequent (e.g., 2 or
more days a week) heartburn.187 Because 1-4 days may be required for complete relief of
symptoms, omeprazole for self-medication is not intended for the immediate relief of
heartburn,187, 188, 189 and other agents (e.g., antacids, histamine H2-receptor antagonists) may be
needed for initial relief.143 However, some individuals may experience complete relief of
symptoms within 24 hours of taking the first dose of omeprazole.187, 188, 189 In 2 controlled
studies, 50% of patients receiving omeprazole 20 mg daily experienced no heartburn during the
first day of therapy, and the percentage of patients experiencing complete relief continued to
increase in subsequent days; 30% of those receiving placebo experienced no heartburn during the
first day of therapy.189 Omeprazole should not be used for self-medication of occasional
heartburn (i.e., heartburn that occurs once weekly or less frequently) or for prevention of
occasional meal- or beverage-induced heartburn.187, 188, 189
Pathologic GI Hypersecretory Conditions
Omeprazole delayed-release capsules are used in adults for the long-term treatment of pathologic
GI hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas,
systemic mastocytosis).1, 2, 3, 4, 5, 8, 13 The drug reduces gastric acid secretion and associated
symptoms (including diarrhea, anorexia, and pain) in patients with these conditions.1, 2, 3, 4, 5, 8, 13
In dosages ranging from 20 mg every other day to 360 mg daily, omeprazole can maintain basal
acid secretion below 5 or 10 mEq/hour in patients who have or have not undergone gastric
surgery, respectively.1 In addition, dosages ranging from 20-360 mg daily have been effective in
resolving acid-related pathology in most patients with Zollinger-Ellison syndrome, including
those whose symptoms were unresponsive to H2-receptor antagonist therapy.8
8

Upper GI Bleeding
Omeprazole oral suspension is used to decrease the risk of upper GI bleeding in critically ill
adults.207, 208, 211 Efficacy of omeprazole was evaluated in a controlled, double-blind randomized
clinical trial in critically ill patients who were randomized to receive either omeprazole oral
suspension (2 doses of 40 mg 6-8 hours apart on the first day, then 40 mg daily) via a gastric
tube or IV cimetidine (300 mg loading dose, then 50-100 mg/hour continuously) for up to 14
days.207, 208, 211 The primary efficacy end point of the study was clinically important upper GI
bleeding (defined as bright red blood that did not clear after tube adjustment and 5-10 minutes of
lavage or positive test for occult blood in gastric aspirate ["coffee ground material"] for 8
consecutive hours on days 1 and 2, or for 2-4 hours on days 3-14 that did not clear with 100 mL
of lavage).207, 208, 211 Omeprazole was at least as effective as IV cimetidine in preventing
clinically important upper GI bleeding.207, 208, 211 In the intent-to-treat population, clinically
important gastric bleeding occurred in 3.9% of patients receiving omeprazole and in 5.5% of
those receiving IV cimetidine.207, 208, 211
Dosage and Administration
Administration
Omeprazole delayed-release capsules and delayed-release tablets for self-administration are
administered orally,1, 187 and the oral suspension is administered orally or through a nasogastric
or orogastric tube.207, 208 To avoid decomposition of omeprazole in the acidic pH of the stomach,
the commercially available delayed-release capsules contain enteric-coated granules of the
drug,1, 2, 4 and the oral suspension contains sodium bicarbonate.207, 208 Patients should be advised
that the capsules must be swallowed intact and not opened, chewed, or crushed.1 However, for
adult and pediatric patients with difficulty swallowing, the capsule may be opened, the contents
carefully emptied on and mixed with a tablespoon of applesauce in a bowl, and the mixture
swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets.1
The applesauce should not be hot and should be soft enough to be swallowed without chewing.1
The applesauce and omeprazole enteric-coated pellet mixture should not be stored for future
use.1 The manufacturer states that the 40 mg capsule, but not the 20 mg capsule, is bioequivalent
when administered with or without applesauce.1 When the contents of a 20 mg capsule were
administered with applesauce, the peak plasma omeprazole concentration decreased by 25%, but
the area under the concentration-time curve (AUC) was not substantially changed. However, the
clinical importance of this is unknown.1 Tablets used for self-medication must be swallowed
intact with a glass of water; the tablets should not be chewed or crushed and should not be
crushed in food.187, 188
Omeprazole powder for oral suspension (Zegerid) should be reconstituted prior to
administration by pouring the contents of a single-dose packet containing 20 or 40 mg of the
drug into a small cup containing 15-30 mL (1-2 tablespoons) of water.207, 208 The suspension
should be stirred well and ingested immediately.207, 208 The cup should be refilled with water and
the contents ingested to ensure complete consumption of the dose.207, 208 The manufacturer states
that omeprazole powder for oral suspension should not be mixed with any liquids (other than
water) or foods.207, 208 If omeprazole powder for oral suspension is to be administered through a
nasogastric or orogastric tube, the contents of each packet should be reconstituted with
approximately 20 mL of water, stirred well and administered immediately.207, 208 An appropriate-

sized syringe should be used to instill the suspension into the tube.207, 208 The suspension should
then be flushed through the tube with 20 mL of water.207, 208
Following administration of delayed-release capsules of omeprazole with meals, the rate of GI
absorption is reduced.3, 5 Therefore, omeprazole should be taken before meals;1, 3, 187, 188, 189
administration up to 2 minutes prior to a meal reportedly has no adverse effect on oral
bioavailability.3 However, since an acidic environment in the parietal cell canaliculi is required
for conversion of proton-pump inhibitors (e.g., omeprazole, lansoprazole) to their active
sulfenamide metabolites,2, 3, 5, 108, 132 the American College of Gastroenterology suggests that
proton-pump inhibitors are most effective when given about 30 minutes prior to meals;
effectiveness may be compromised if these drugs are administered during the basal state (e.g., to
fasting patients at bedtime) or concomitantly with other antisecretory agents (e.g.,
anticholinergics, histamine H2-receptor antagonists, somatostatin analogs, misoprostol).5, 108, 132
Antacids may be administered concomitantly with omeprazole delayed-release capsules.1, 3
The manufacturer of omeprazole oral suspension states that the preparation should be
administered on an empty stomach at least 1 hour prior to a meal.207, 208 For patients receiving
continuous feedings via a nasogastric or orogastric tube, enteral feeding should be stopped
temporarily for 3 hours before, and for 1 hour after administration of omeprazole oral
suspension.207, 208 Also, the manufacturer states that antacids, antacid/alginic acid combinations,
histamine H2-receptor antagonists, or histamine H2-receptor antagonist and antacid combinations
may be used for "breakthrough" symptoms; however, efficacy of these agents for this use has not
been established.208
Omeprazole usually is administered once daily in the morning;1, 3, 6, 7, 9, 10, 12, 187, 188, 189 however,
administering the drug in divided doses (e.g., every 12 hours) has been reported to improve
efficacy in patients receiving more than 80 mg daily.13
Dosage
The manufacturer states that omeprazole dosage adjustments based on age are not necessary in
geriatric patients.1, 207, 208 However, since the bioavailability of omeprazole appears to be
increased substantially in Asians, the manufacturer states that dosage adjustment should be
considered in Asian patients, especially when such patients are receiving long-term omeprazole
therapy for maintenance of healing of erosive esophagitis.1, 207, 208 There is no evidence from the
omeprazole prescription safety database that Asians experience excess risk from omeprazole, or
that accumulation of omeprazole in the blood is harmful when used over a short period of time
(e.g., 14 days of self-medication) in Asian patients.189
Dosage of omeprazole magnesium is expressed in terms of omeprazole.187
Duodenal Ulcer
For the short-term treatment of active duodenal ulcer, the usual adult dosage of omeprazole is 20
mg once daily.1, 2, 207, 208 Therapy should be continued until healing occurs, usually within 2-4
weeks; some patients may benefit from an additional 4 weeks of therapy.1, 2, 207, 208 Occasionally,
dosages up to 40 mg daily may be necessary in patients who have been poorly responsive to
therapy with H2-receptor antagonists.2

10

When omeprazole is used in combination with clarithromycin (dual therapy) for the treatment of
Helicobacter pylori infection in patients with active duodenal ulcer, the usual adult dosage of
omeprazole is 40 mg once daily (in the morning) for 14 days.1 In patients who have an active
ulcer present at the time anti-H. pylori therapy is initiated, an additional 14 days of therapy with
omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.1 When
omeprazole is used in combination with clarithromycin and amoxicillin (triple therapy) for the
treatment of H. pylori infection in patients with active duodenal ulcer, the usual adult dosage of
omeprazole is 20 mg twice daily (morning and evening) for 10 days.1 In patients who have an
active ulcer present at the time anti-H. pylori therapy is initiated, an additional 18 days of therapy
with omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.1
Multiple-drug regimens currently recommended by the American College of Gastroenterology
(ACG) and many clinicians for the treatment of H. pylori infection consist of a proton-pump
inhibitor (e.g., omeprazole) and 2 anti-infective agents (e.g., clarithromycin and amoxicillin or
metronidazole) or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline)
concomitantly with a proton-pump inhibitor; when omeprazole has been used in these regimens,
dosages of 20 mg once daily to 80 mg twice daily (generally 20 mg twice daily) for 7-28 days
have been used.106, 108, 111, 112, 113, 115 While the minimum duration of therapy required to
eradicate H. pylori infection with these 3- or 4-drug regimens has not been fully elucidated,27, 28,
29, 32
the ACG and many clinicians state that treatment for longer than 1 week probably is not
necessary. However, more prolonged therapy is recommended for patients with complicated,
large, or refractory ulcers; therapy in such patients should be continued at least until successful
eradication of H. pylori has been confirmed.108, 112 (See Uses: Helicobacter pylori Infection, in
Clarithromycin 8:12.12.92.)
Gastric Ulcer
For the short-term treatment of active benign gastric ulcer, the usual adult dosage of omeprazole
is 40 mg once daily for 4-8 weeks.1, 207, 208
Gastroesophageal Reflux
For the short-term, symptomatic treatment of gastroesophageal reflux disease (GERD) without
erosive esophageal lesions, the usual adult dosage of omeprazole is 20 mg once daily for 4
weeks.1, 2, 207, 208 For the short-term treatment of erosive esophagitis, the usual adult dosage of
omeprazole is 20 mg once daily for 4-8 weeks.1, 2, 207, 208 Occasionally, dosages up to 40 mg
daily may be necessary in some patients.2, 98 Therapy is continued until healing occurs, usually
within 4-8 weeks; an additional 4 weeks of therapy (up to 12 weeks for a single course) may
contribute to healing and symptomatic improvement in some patients.1, 2, 98, 207 If erosive
esophagitis or symptomatic GERD (heartburn) recurs, the manufacturer states that additional 4to 8-week courses of omeprazole may be considered.1, 207 However, the American College of
Gastroenterology (ACG) states that chronic, even lifelong, therapy with a proton-pump inhibitor
is appropriate in many patients with GERD.143
For maintenance therapy following healing of erosive esophagitis to reduce recurrence, the usual
adult dosage of omeprazole is 20 mg daily.1, 207, 208 Safety and efficacy of omeprazole
maintenance therapy for longer than 1 year have not been established.1, 207
For the treatment of symptomatic GERD or erosive esophagitis and for maintenance of healing
of erosive esophagitis in pediatric patients 2-16 years of age, a dosage of 10 mg of omeprazole
11

daily is recommended for children weighing less than 20 kg, and 20 mg daily is recommended
for those weighing 20 kg or more.1, 198 Omeprazole was administered as a single daily dose for 4
weeks in one study of children with symptomatic nonerosive GERD.1, 198 On a mg/kg basis, the
dosage of omeprazole required to heal erosive esophagitis is greater in pediatric patients than that
required in adults.1, 197, 198 In an uncontrolled open-label study, dosages of 0.7-3.5 mg/kg daily
(up to a maximum dosage of 80 mg daily) for 3-6 months were required for healing in children
1-16 years of age; a dosage of 0.7 mg/kg daily resulted in healing of erosive esophagitis in 44%
of children, but a dosage of 1.4 mg/kg daily was required for healing to occur in an additional
28% of the children.1, 197, 198 In an uncontrolled open-label study of 46 pediatric patients, dosages
of omeprazole for maintenance therapy following healing of erosive esophagitis were half those
required for initial healing in 54% of children, but the remainder required an increased dosage
(0.7 to a maximum of 2.8 mg/kg daily) for all or part of the maintenance period;1, 198
maintenance therapy was continued for about 2 years.1, 198
Self-Medication
For self-medication to relieve symptoms of frequent heartburn in adults 18 years of age or older,
an omeprazole dosage of 20 mg once daily in the morning for 14 days is recommended.187, 188
For self-medication, the manufacturer recommends that the dosage of omeprazole not exceed 20
mg in 24 hours.187 In addition, the drug should not be used for self-medication for longer than 14
days of continuous use and individuals should not exceed one course of therapy every 4 months
unless otherwise directed by a clinician.187, 188
Pathologic GI Hypersecretory Conditions
For the treatment of pathologic GI hypersecretory conditions (e.g., Zollinger-Ellison syndrome,
multiple endocrine adenomas, systemic mastocytosis), dosages of omeprazole should be
individualized according to patient response and tolerance.1, 2, 13 The usual initial adult dosage is
60 mg (as delayed-release capsules) once daily.1, 2 Subsequent omeprazole dosage should be
adjusted as tolerated and necessary to adequately suppress gastric acid secretion, and therapy
continued as long as clinically necessary.1 Daily dosages exceeding 80 mg should be
administered in divided doses.1, 13
Oral dosages ranging from 20 mg every other day to 360 mg daily (given in 3 divided doses)
have been necessary to maintain basal gastric acid secretion at less than 10 mEq/hour in patients
without a history of gastric surgery and less than 5 mEq/hour in those who have undergone
gastric surgery;1, 2 determination of gastric acid secretion during the hour prior to a dose may be
useful in establishing optimum dosage.2, 13 Omeprazole has been given continuously for more
than 5 years in some patients with Zollinger-Ellison syndrome.1, 2
Upper GI Bleeding
For reduction of risk of upper GI bleeding in critically ill adults, the initial loading dose of
omeprazole is 40 mg (as oral suspension) followed by another 40-mg dose after 6-8 hours on the
first day; thereafter, 40 mg (as oral suspension) once daily for up to 14 days.207 Safety and
efficacy of omeprazole oral suspension in critically ill patients for longer than 14 days have not
been established.207
Dosage in Renal and Hepatic Impairment

12

Although pharmacokinetics may be altered in patients with renal impairment, dosage adjustment
does not appear necessary in patients with such impairment.1, 3, 4 However, the manufacturer
states that dosage adjustment should be considered in patients with hepatic impairment,
particularly in such patients receiving long-term omeprazole therapy for maintenance or healing
of erosive esophagitis.1 Some clinicians recommend that such patients with hepatic dysfunction
receiving dosages exceeding 20 mg daily should be monitored closely for possible adverse
effects.3
Cautions
Omeprazole generally is well tolerated.1, 2, 3, 5, 6, 187, 188, 207, 208 The most frequent adverse effects
associated with omeprazole therapy involve the GI tract (e.g., diarrhea, nausea, constipation,
abdominal pain, vomiting) and the CNS (e.g., headache, dizziness).1, 2, 3, 207, 208 In short-term
studies, the incidence of reported adverse effects was similar in patients receiving omeprazole or
placebo.1, 2, 6, 8, 207, 208 In addition, while the most common effects have been reported in 1-7% of
patients receiving omeprazole, they were considered by investigators as being possibly,
probably, or definitely related to the drug in only 0.2-2.4% of patients.1, 207, 208 Overall, the
frequency and type of adverse effects produced by omeprazole appear to be similar to those
produced by ranitidine,1, 2, 3, 8, 9, 207, 208 and the frequency of omeprazole-induced effects does not
appear to be affected by age in adults.1, 2 In dose-ranging studies, a relationship between doses
ranging from 10-60 mg and the frequency of adverse effects was not observed.2 Adverse effects
were severe enough to result in discontinuance of omeprazole therapy in less than 2% of patients
in clinical studies.2, 3 The manufacturer states that administration of delayed-release capsules of
omeprazole generally was well tolerated in pediatric patients with an adverse event profile
similar to that in adults.1 However, the most frequently reported adverse effects in pediatric
patients were respiratory effects, which were reported in about 46 or 18% of those 0-2 or 2-16
years of age, respectively; otitis media also was frequently reported in children 0-2 years of age,
and accidental injuries were frequently reported in those 2-16 years of age.1
In controlled clinical trials with combined omeprazole-clarithromycin or omeprazoleclarithromycin-amoxicillin therapy, no adverse drug experiences peculiar to these combinations
were noted.1
In a controlled clinical trial, the adverse event profile was similar for critically ill patients
receiving either omeprazole suspension or IV cimetidine for up to 14 days.207, 208 The most
frequent adverse effects reported in patients receiving omeprazole were pyrexia (20.2%),
hypokalemia (12.4%), nosocomial pneumonia (11.2%), hyperglycemia (10.7%),
thrombocytopenia (10.1%), hypomagnesemia (10.1%), and hypotension (9.6%).207, 208
GI Effects
Diarrhea,1, 2, 3, 5, 6, 7, 12, 207, 208 abdominal pain,1, 2, 3, 12, 207, 208 nausea,1, 2, 3, 5, 6, 12, 207, 208
vomiting,1, 2, 3, 6, 12, 207, 208 constipation,1, 2, 3, 7, 207, 208 flatulence,1, 207, 208 and acid regurgitation1,
207, 208
are the most frequent adverse GI effects reported with omeprazole therapy, occurring in
about 1-5% of patients.1, 207, 208 Constipation, diarrhea, and gastric hypomotility occurred in 4.5,
3.9, and 1.7%, respectively, of critically ill patients receiving omeprazole oral suspension or in
4.4, 8.3, and 3.3%, respectively, of those receiving IV cimetidine in a controlled clinical trial.207,
208
Dysphagia,2 abdominal swelling, anorexia, irritable colon, fecal discoloration, pancreatitis
13

(sometimes fatal),1 esophageal candidiasis, mucosal atrophy of the tongue, taste perversion, dry
mouth, and stomatitis have been reported in less than 1% of patients in clinical studies and/or
during postmarketing surveillance; a causal relationship to the drug was not established in many
cases.1, 207 Benign gastric fundic polyps have been reported rarely and appear to resolve upon
discontinuation of omeprazole therapy.1, 207 Long-term administration of omeprazole has
produced dose-related increases in gastric carcinoid tumors and enterochromaffin-like (ECL) cell
hyperplasia in rats.1, 2, 3, 8, 22, 98, 207 Carcinoid tumors also have been observed in rats subjected to
fundectomy or long-term treatment with other proton-pump inhibitors or high dosages of H2receptor antagonists.1, 207 Gastric biopsy specimens obtained from patients in long-term studies
with omeprazole have demonstrated an increased frequency of ECL cell hyperplasia.1, 207
However, no cases of ECL cell carcinoid tumor, dysplasia, or neoplasia were found.1, 207 (See
Cautions: Mutagenicity and Carcinogenicity.)
As with other agents that elevate intragastric pH, administration of omeprazole for 14 days in
healthy individuals increased the intragastric concentration of viable bacteria.1, 207 The pattern of
bacteria isolated was similar to that of saliva.1, 207 Alterations in the intragastric bacterial flora
were reversible following discontinuance of omeprazole.1, 207
Adverse GI effects observed in controlled trials with combined omeprazole and clarithromycin
therapy that were not reported with omeprazole monotherapy include taste perversion in 15% of
such patients and tongue discoloration in 2%.1
Nervous System Effects
Headache1, 2, 3, 5, 6, 9, 12, 207, 208 and dizziness1, 2, 3, 5, 9, 12, 207, 208 are the most common adverse
nervous system effects of omeprazole, occurring in 6.9 and 1.5%, respectively, of patients in US
clinical studies.1, 207, 208 In a controlled clinical trial in critically ill patients, agitation occurred in
3.4 or 8.8% of patients receiving omeprazole oral suspension or IV cimetidine, respectively.
Asthenia1 has been reported in 1.1-1.3% of patients receiving omeprazole; in controlled studies,
the incidence of this effect was similar in patients receiving omeprazole, ranitidine, or placebo.1,
207, 208
Psychic disturbances, including depression, agitation, aggression, hallucinations,
confusion, insomnia, nervousness, tremors, apathy, somnolence, anxiety, and dream
abnormalities, have been reported in less than 1% of patients receiving omeprazole in clinical
studies and/or during postmarketing surveillance; a causal relationship to the drug was not
established in many cases.1, 207 Other infrequent nervous system effects for which a causal
relationship may not have been established include pain, fatigue, malaise, vertigo, paresthesia,
and hemifacial dysesthesia.1, 207
Respiratory Effects
Upper respiratory tract infections and cough1, 12, 207, 208 have occurred in 1.9 and 1.1%,
respectively, of patients receiving omeprazole; in controlled studies, the incidence of these
effects was similar in patients receiving omeprazole, ranitidine, or placebo.1, 207, 208 Acute
respiratory distress syndrome, respiratory failure, and pneumothorax occurred in 3.4, 1.7, and
0.6%, respectively, of critically ill patients receiving omeprazole oral suspension, or in 3.9, 3.3,
and 4.4%, respectively, of those receiving IV cimetidine in a controlled clinical trial.207 Epistaxis
and pharyngeal pain have been reported in less than 1% of patients in clinical studies and/or
during postmarketing surveillance; a causal relationship to the drug was not established.1, 207

14

Adverse respiratory effects have been reported in about 46% of children 0-2 years of age and in
about 18% of those 2-16 years of age.1, 198
Other adverse respiratory effects observed in controlled trials with combined omeprazole and
clarithromycin therapy that were not reported with omeprazole monotherapy were rhinitis in 2%
of patients, pharyngitis in 1%, and flu syndrome in 1%.1
Community-acquired Pneumonia
Administration of gastric antisecretory agents (e.g., proton-pump inhibitors, H2-receptor
antagonists) has been associated with an increased risk for developing certain infections (e.g.,
community-acquired pneumonia).199 A possible association between chronic administration of
gastric acid-suppressive drugs and occurrence of community-acquired pneumonia has been
evaluated using a large Dutch database (Integrated Primary Care Information [IPCI]) containing
information on approximately 500,000 patients, 364,683 of whom (average follow-up: 2.7 years)
were selected for evaluating any such association.199 During the 8-year population-based, casecontrol study, gastric acid suppressants were first prescribed in 19,459 individuals (12,337
received proton-pump inhibitors [mean duration of use: 5 months] and 10,177 received H2receptor antagonists [mean duration of use: 2.8 months]; some individuals received both
drugs).199 Most patients did not undergo endoscopy and were treated empirically for upper GI
symptoms.199 In this study, first occurrence of pneumonia (confirmed by radiography or
microbiologic testing in 18% of patients) was reported in 5551 individuals;199 development of
pneumonia occurred in 185 individuals while receiving gastric acid suppressants and in 292
individuals who had discontinued such use.199
The adjusted relative risk for development of pneumonia (or the incidence rate) was 0.6, 2.3 and
2.5 per 100 person-years for individuals not receiving acid-suppressive drugs, for those receiving
H2-receptor antagonists, and for those receiving proton-pump inhibitors, respectively.199 Patients
using gastric acid suppressants developed community-acquired pneumonia 4.5 (95% confidence
interval of 3.8-5.1) times more often than those who never used such drugs.199 When evaluating
use of all gastric acid suppressants, current use of the drugs was associated with a small (27%)
overall increase in the risk of pneumonia (adjusted odds ratio 1.27 and 95% confidence interval
of 1.06-1.54).199 Higher risks were observed for current users of proton-pump inhibitors and H2receptor antagonists;199 the adjusted relative risk for developing community-acquired pneumonia
was 1.89 (95% confidence interval of 1.36-2.62) or 1.63 (95% confidence interval of 1.07-2.48),
respectively, for these classes of drugs compared with those who discontinued using these
agents.199 Estimates for developing pneumonia were higher (2.2 [95% confidence interval of 1.43.5] for proton-pump inhibitors and 1.7 [95% confidence interval of 0.8-2.9] for H2-receptor
antagonists) when only laboratory-confirmed cases of pneumonia were considered for
analysis.199
Although there was variation among individual proton-pump inhibitors and individual H2receptor antagonists, the numbers were small and the heterogeneity was not considered
significant.199 For patients currrently receiving proton-pump inhibitors, a dose-response
relationship for developing pneumonia was observed; individuals using more than one defined
daily dose of these drugs had a 2.3-fold increased risk for developing pneumonia compared with
those who discontinued gastric acid suppressants.199, 200 Such a dose-response relationship for
developing pneumonia was not observed in patients receiving H2-receptor antagonists; however,
15

dose variation of these drugs was limited.199 Among current users of proton-pump inhibitors or
H2-receptor antagonists, the risk for developing pneumonia was most pronounced among those
who initiated such therapies within the past 30 days.199
Although the exact mechanism for development of community-acquired pneumonia in patients
receiving gastric acid suppressants has not been fully elucidated, it has been suggested that
reduction of gastric acid secretion by acid suppressive therapy and consequent increases of
gastric pH may result in a favorable environment for the development of infection.199, 200
Intragastric acidity constitutes a major nonspecific defense mechanism of the stomach to
ingested pathogens; when gastric pH is less than 4, most pathogens are killed, while at higher
gastric pH, pathogens may survive.199 Since intragastric pH should be maintained above 4 for
several hours for the effective management of upper GI symptoms, acid suppressive therapy may
lead to insufficient elimination or even increased colonization of ingested pathogens.199 Some
evidence indicates that acid-supressive therapy may result in nosocomial infections.199
It should be considered that certain patients (e.g., those with pleuritic chest pain, hypothermia,
systolic hypotension, tachypnea, diabetes mellitus, neoplastic disease, neurologic disease,
bacteremia, leukopenia, multilobar pulmonary infiltrate) are at increased risk for developing
infections and in these individuals community-acquired pneumonia may be associated with
increased mortality.199, 201 199 Some clinicians state that gastric acid-suppressive drugs should be
used in patients in whom community-acquired pneumonia may be severe (e.g., those with asthma
or chronic obstructive lung disease, immunocompromised patients, pediatric or geriatric
individuals) only when clearly needed and the lowest effective dose should be employed.199
Musculoskeletal Effects
Back pain has been reported in about 1% of patients receiving omeprazole.1 Other
musculoskeletal effects have occurred in less than 1% of patients in clinical studies and/or
postmarketing surveillance; a causal relationship to the drug was not established in many cases.1,
207
Such effects include muscle cramps, myalgia, muscle weakness, joint pain,1, 89, 207 and leg
pain.1, 207
Limited observational data suggest that long-term use of proton-pump inhibitors, particularly in
high dosages, may increase the risk of hip fracture in patients older than 50 years of age.212 In a
nested case-control analysis consisting of users of proton-pump inhibitors and nonusers of acid
suppression therapy (i.e., proton-pump inhibitors, histamine H2-receptor antagonists) selected
from within an eligible study cohort of 1.8 million individuals,212 the risk of hip fracture in cases
(patients receiving at least 1 year of therapy with a proton-pump inhibitor) was higher (odds ratio
1.44, adjusted for multiple confounding factors such as body mass index, known associations
with osteoporosis, and comorbid conditions) than that in controls (patients who did not receive
acid suppression therapy).212 Risk of hip fracture was markedly increased (adjusted odds ratio,
2.65) in patients receiving long-term, high-dose (greater than a mean of 1.75 doses daily) therapy
with proton-pump inhibitors.212 In addition, the strength of the association increased with
increasing duration of proton-pump inhibitor therapy (adjusted odds ratios of 1.22, 1.41, 1.54,
and 1.59 for durations of 1, 2, 3, or 4 years of such therapy, respectively).212 (See Cautions:
Precautions and Contraindications.)
Hepatic Effects
16

Mild and, rarely, marked increases in serum ALT (SGPT), AST (SGOT), -glutamyltransferase
(GGT, -glutamyltranspeptidase, GGTP), alkaline phosphatase, and bilirubin concentrations1, 3,
21, 207
have been reported in less than 1% of patients receiving omeprazole, but in many cases a
causal relationship has not been established.1, 207 In a controlled clinical trial in critically ill
patients, abnormal liver function test results (not otherwise specified) occurred in 1.7 or 3.3% of
patients receiving omeprazole oral suspension or IV cimetidine, respectively.207 Rare
occurrences of symptomatic liver disease have been reported, including hepatocellular,
cholestatic, or mixed hepatitis, liver necrosis, hepatic failure, and hepatic encephalopathy.1, 207
Fatalities have been reported in some patients with hepatic failure or liver necrosis.1, 207
Dermatologic and Sensitivity Reactions
In a controlled clinical trial in critically ill patients, and decubitus ulcer occurred in 5.6 and 3.4%,
respectively, of patients receiving omeprazole oral suspension or in 6.1 and 2.8%, respectively,
of those receiving IV cimetidine.207, 208
Rash has been reported in less than 1% of patients receiving omeprazole in clinical studies
and/or during postmarketing surveillance;1, 2, 9, 12, 207 rarely, severe generalized reactions such as
toxic epidermal necrolysis (TEN) (some fatal),1, 23, 207 Stevens-Johnson syndrome,1, 207 erythema
multiforme,1, 207 exfoliative dermatitis,88 and lichenoid eruptions have been reported.2, 14, 207
Other adverse dermatologic effects occurring in less than 1% of patients in clinical studies and/or
during postmarketing surveillance include skin inflammation,1, 207 urticaria,1, 91, 207 purpura
and/or petechiae (some cases with rechallenge)1, 207 angioedema,1, 91, 207 pruritus,1, 91, 207
photosensitivity,1 alopecia,1, 207 dry skin,1, 207 and hyperhidrosis.1, 207 Allergic reactions,
including rare cases of anaphylaxis, have been reported with omeprazole therapy.1, 207 In many
cases, a causal relationship to omeprazole has not been established.1, 207
Hematologic Effects
Short-term use of omeprazole does not appear to be associated with substantial changes in
hematologic parameters.2 However, in a controlled clinical trial of critically ill patients,
thrombocytopenia, anemia, and aggravated anemia occurred in 10.1, 7.9 and 2.2%, respectively,
of those receiving omeprazole oral suspension, or in 6.1, 7.7, and 3.9%, respectively, of those
receiving IV cimetidine.207, 208 Agranulocytosis (occasionally fatal) has been reported rarely with
omeprazole therapy, but a causal relationship to the drug is uncertain.1, 207 Other adverse
hematologic effects reported in less than 1% of patients receiving the drug in clinical studies
and/or during postmarketing surveillance include pancytopenia, thrombocytopenia, neutropenia,
leukopenia, anemia, and leukocytosis.1, 207 Hemolytic anemia has been reported rarely in patients
receiving omeprazole.1, 2, 3, 15, 207 In many cases, a causal relationship with omeprazole has not
been established.1, 207
Genitourinary Effects
Acute interstitial nephritis (some cases with positive rechallenge)1, 16, 17, 24, urinary tract
infection, microscopic pyuria, urinary frequency, elevated serum creatinine concentration,
proteinuria, hematuria, glycosuria, testicular pain, and gynecomastia,1, 2, 3, 20, 207 occurred in less
than 1% of patients receiving omeprazole in clinical studies and/or during postmarketing
surveillance; in many cases a causal relationship to the drug has not been established.1, 207 Sexual
disturbances3, 18, 19 (e.g., priapism)98 have been reported occasionally in patients receiving
omeprazole.
17

Cardiovascular Effects
In a controlled clinical trial of critically ill patients, hypotension and hypertension occurred in 9.6
and 7.9%, respectively, of patients receiving omeprazole oral suspension, or in 6.6 and 3.3%,
respectively, of those receiving IV cimetidine.207, 208 Atrial fibrillation, ventricular tachycardia,
bradycardia, supraventricular tachycardia and tachycardia (not otherwise specified) occurred in
6.2, 4.5, 3.9, 3.4, and 3.4%, respectively, of patients receiving omeprazole oral suspension, or in
3.9, 3.3, 2.8, 1.1, and 3.3%, respectively, of patients receiving IV cimetidine.207, 208
Chest pain, angina pectoris, tachycardia, bradycardia, palpitation, elevated blood pressure, and
peripheral edema have been reported in less than 1% of patients receiving omeprazole in clinical
studies and/or during postmarketing surveillance; a causal relationship to the drug has not been
established in many cases.1, 207
Although preliminary safety data from 2 long-term clinical trials comparing omeprazole or
esomeprazole with antireflux surgery in patients with severe gastroesophageal reflux disease
(GERD) raised concerns about a potential increased risk of cardiac events (myocardial
infarction, heart failure, and sudden death) in patients receiving these drugs, the US Food and
Drug Administration (FDA) has reviewed safety data from these and other studies of the drugs
and has concluded that long-term use of omeprazole or esomeprazole is not likely to be
associated with an increased risk of such cardiac events.213, 214, 215 FDA has concluded that the
apparent increase in cardiac events observed in the early analyses is not a true effect of the
drugs.213, 214, 215
In one study (a 14-year study comparing omeprazole with antireflux surgery in 298 patients),
death from cardiac causes (heart failure, sudden death) or nonfatal myocardial infarction
occurred in 8 or 9 patients, respectively, randomized to receive omeprazole and in 2 or 2
patients, respectively, randomized to undergo surgery.214 However, the findings may have been
biased by baseline differences between the 2 groups, since patients in the surgery group tended to
be younger and healthier and were less likely to have a history of myocardial infarction than
those receiving omeprazole.214, 215 In addition, some patients withdrew from the study prior to
undergoing surgery, and several underwent surgery and also received drug therapy.214, 215 Fewer
than half of the patients remained in the study until its completion.214 Preliminary data from the
second study (an ongoing study comparing esomeprazole with antireflux surgery in 554 patients)
also suggested a difference in occurrence of cardiac events between treatment groups; however,
after 5 years of follow-up, a similar number of patients in each treatment group had experienced
cardiac-related events.214 FDA reviewed safety data from 14 additional comparative studies of
omeprazole (including 4 placebo-controlled studies) and indicated that these studies do not
suggest that omeprazole is associated with an increased risk of cardiac events.213, 214, 215 None of
the studies were designed to assess cardiac risk, and patient follow-up in the studies was
incomplete.213, 214, 215
Ocular Effects
Blurred vision, ocular irritation, dry eye syndrome, optic atrophy, anterior ischemic optic
neuropathy, optic neuritis, and double vision have been reported in less than 1% of patients
receiving omeprazole in clinical studies and/or during postmarketing surveillance; in many cases
a causal relationship to the drug has not been established.1, 207

18

Other Adverse Effects


In a controlled clinical trial of critically ill patients, hypophosphatemia, hypocalcemia, fluid
overload, and hyponatremia occurred in 6.2, 6.2, 5.1, and 3.9%, respectively, of patients
receiving omeprazole oral suspension or in 3.9, 5.5, 7.7, and 2.8%, respectively, of patients
receiving IV cimetidine.207, 208 Hypoglycemia, hyperkalemia, and hypernatremia occurred in 3.4,
2.2, and 1.7%, respectively, of those receiving omeprazole or in 4.4, 3.3, and 5%, respectively, of
patients receiving IV cimetidine.207, 208 Hyperpyrexia and edema occurred in 4.5 and 2.8%,
respectively, of patients receiving omeprazole oral suspension or in 1.7 and 6.1%, respectively,
of patients receiving IV cimetidine.207, 208 Sepsis (not otherwise specified), oral candidiasis,
urinary tract infection, and candidal infection (not otherwise specified) occurred in 5.1, 3.9, 2.2,
and 1.7%, respectively, of patients receiving omeprazole oral suspension or in 5, 0.6, 3.3, and
3.9%, respectively, of patients receiving IV cimetidine.207, 208
Hyponatremia, hypoglycemia, weight gain, fever, and tinnitus have been reported in less than
1% of patients receiving omeprazole in clinical studies and/or during postmarketing surveillance,
but in many cases were not attributed to the drug.1, 207 Acute gout also has been reported during
omeprazole therapy.87
Otitis media occurred in about 23% of pediatric patients 0-2 years of age, and accidental injury
occurred in about 4% of those 2-16 years of age in clinical studies.1, 198
Limited evidence suggests that omeprazole therapy may cause a dose-dependent reduction in
cyanocobalamin absorption,86, 98, 99, 100, 101 although conflicting data also exist.102 In one study,
absorption of protein-bound cyanocobalamin decreased from a median value of 2.2 or 2.3% at
baseline to 0.8 or 0.5% in healthy men receiving 20 or 40 mg, respectively, of omeprazole daily
for 2 weeks.99 (See Cautions: Precautions and Contraindications.)
Another adverse effect observed in controlled trials with combined omeprazole and
clarithromycin therapy that was not reported with omeprazole monotherapy was flu syndrome,
which occurred in 1% of patients receiving such combined therapy.1
Precautions and Contraindications
Symptomatic response to omeprazole should not be interpreted as precluding the presence of
gastric malignancy.1, 207, 208
While available endoscopic and histologic examinations of gastric biopsy specimens from
humans exposed short-term to omeprazole have failed to reveal any associated risk,1, 2, 3, 8 a
dose-related increase in gastric carcinoid tumors has been observed during long-term exposure in
animals,1, 2, 3, 8, 207 and further data from humans are needed to rule out the possibility of an
increased risk of tumors during long-term exposure to the drug.1, 97 (See Cautions: Mutagenicity
and Carcinogenicity.)
Atrophic gastritis occasionally has been noted in gastric corpus biopsies from patients receiving
long-term treatment with omeprazole.1, 207, 208
The possibility that gastric acid-suppressive therapy may increase the risk of communityacquired pneumonia should be considered. (See Respiratory Effects: Community-acquired
Pneumonia, in Cautions.)
19

Data from an observational study suggests that long-term therapy with a proton-pump inhibitor,
particularly in high dosages, may increase the risk of hip fracture in patients older than 50 years
of age.212 (See Cautions: Musculoskeletal Effects.) While controlled studies are required to
confirm these findings, clinicians should use the lowest effective dosage of a proton-pump
inhibitor for appropriate indications and consider employing strategies to increase calcium intake
(e.g., increased calcium dosage, administration of insoluble calcium supplements with food) in
older patients who require long-term, high-dose therapy with these drugs.212
Although preliminary safety data from 2 long-term clinical trials comparing omeprazole or
esomeprazole with antireflux surgery in patients with severe gastroesophageal reflux disease
(GERD) raised concerns about a potential increased risk of cardiac events (myocardial
infarction, heart failure, and sudden death) in patients receiving these drugs, FDA has reviewed
safety data from these and other studies of the drugs and has concluded that long-term use of
omeprazole or esomeprazole is not likely to be associated with an increased risk of such cardiac
events.213, 214, 215 FDA has concluded that the apparent increase in cardiac events observed in the
early analyses is not a true effect of the drugs and recommends that clinicians continue to
prescribe and patients continue to use these drugs in the manner described in the manufacturers'
labelings.213, 214, 215 (See Cautions: Cardiovascular Effects.)
Omeprazole can prolong the elimination of diazepam, warfarin (the R-isomer), and phenytoin,
and the possibility that dosages of these and other drugs that are metabolized by cytochrome P450-mediated oxidation in the liver may require adjustment should be considered when
concomitant omeprazole therapy is initiated or discontinued.1, 2, 207, 208 Increases in international
normalized ratio (INR) and prothrombin time have been reported in patients receiving warfarin
concomitantly with a proton-pump inhibitor, including omeprazole.1, 134, 139, 207, 208 Because such
increases may lead to abnormal bleeding and death, INR and prothrombin time may need to be
monitored in patients receiving warfarin and a proton-pump inhibitor concomitantly.1, 134, 139, 207,
208
In addition, the possibility that omeprazole-induced increases in gastric pH may affect the
bioavailability of drugs such as ketoconazole, ampicillin esters, or iron salts (where gastric
acidity is an important determinant in oral absorption) also should be considered.1, 207, 208
Each 20- or 40-mg packet of omeprazole powder for oral suspension (Zegerid) contains 1680
mg of sodium bicarbonate (460 mg [20 mEq] of sodium).207, 208 The sodium content of Zegerid
should be taken into consideration in patients whose sodium intake must be restricted; increased
sodium intake may produce edema and weight increase.207, 208 Sodium bicarbonate may cause
metabolic alkalosis, seizures, and tetany, and chronic use with calcium or milk may cause milkalkali syndrome.207, 208 Acute toxicity associated with sodium bicarbonate overdose may include
hypocalcemia, hypokalemia, hypernatremia, and seizures.207, 208 Sodium bicarbonate should be
used with caution in patients with Bartter's syndrome, hypokalemia, respiratory alkalosis, or
acid-base abnormalities.207, 208 Sodium bicarbonate is contraindicated in patients with metabolic
alkalosis or hypocalcemia.207, 208
In clinical trials in patients who received combined clarithromycin-omeprazole therapy for H.
pylori infection, some H. pylori isolates demonstrated an increase in clarithromycin MICs over
time, indicating decreased susceptibility and increasing resistance to the drug.105 Susceptibility
testing should be performed if possible in patients with H. pylori infection in whom therapy with
combined clarithromycin-omeprazole fails (i.e., as determined in clinical trials by a positive
20

result for H. pylori on culture or histologic testing 4 weeks following completion of therapy);130
if resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative
anti-infective therapy should be instituted.105 The American College of Gastroenterology (ACG)
states that clarithromycin or metronidazole should not be used subsequently in patients with H.
pylori infection who fail therapy that includes these drugs since resistance consistently emerges
during such unsuccessful therapy.108 (See Uses: Helicobacter pylori Infection, in Clarithromycin
8:12.12.92.)
Concomitant administration of clarithromycin (500 mg 3 times daily) and omeprazole (40 mg
daily) in healthy men resulted in increases of 30, 89, and 34% in the peak plasma concentration,
area under the concentration-time curve (AUC), and elimination half-life, respectively, of
omeprazole.1 Increases in omeprazole AUC and half-life had a modest effect on gastric pH;
mean 24-hour gastric pH was 5.2 when omeprazole was administered alone versus 5.7 with
concomitant administration of clarithromycin.106, 131 Acid suppression resulting from omeprazole
appears to enhance the activity of anti-infective therapy against H. pylori. Serum concentrations
and areas under the concentration-time curve (AUCs) of clarithromycin and 14hydroxyclarithromycin also are increased by concomitant administration of omeprazole.105, 131
(See Pharmacokinetics: Absorption, in Clarithromycin 8:12.12.92.)
Limited data suggest that omeprazole therapy may cause a dose-dependent reduction in
cyanocobalamin absorption.86, 98, 99, 100, 101 (See Cautions: Other Adverse Effects.) Whether such
a reduction in cyanocobalamin absorption can result in a deficiency of the vitamin has not been
determined, although it has been suggested that pending further study, serum cyanocobalamin
concentrations should be monitored in patients receiving long-term therapy with omeprazole.99
Patients should be advised to consult their clinician before using omeprazole for self-medication
if they are taking warfarin, an antifungal agent (e.g., ketoconazole), diazepam, or digoxin.187
Patients with heartburn that has persisted for more than 3 months or heartburn in conjunction
with lightheadedness, sweating, or dizziness should consult their clinician before using
omeprazole for self-medication.187 Patients should be advised to consult their clinician before
using omeprazole for self-medication if they are experiencing chest or shoulder pain with
lightheadedness, shortness of breath, sweating, or pain spreading to arms, neck, or shoulders.187
Those with frequent chest pain, unexplained weight loss, nausea and vomiting, stomach pain, or
frequent wheezing (especially with heartburn) also should consult their clinician before using
omeprazole for self-medication.187 Patients should discontinue taking omeprazole for selfmedication and consult their clinician if heartburn persists, or worsens after 14 days of therapy,
or a course of treatment is needed more frequently than every 4 months.187 Patients with
difficulty or pain with swallowing, vomiting with blood, or bloody or blackened stools should
not use omeprazole for self-medication; such manifestations should be reported promptly to a
clinician, since they may be indicative of a serious condition requiring alternative treatment.187
Women who are pregnant or breast feeding should consult their clinician before using
omeprazole for self-medication.187
Omeprazole is contraindicated in patients with known hypersensitivity to the drug,
esomeprazole, or other substituted benzimidazoles (e.g., lansoprazole, pantoprazole,
rabeprazole), or any ingredient in the formulation.1, 25, 139

21

Pediatric Precautions
Safety and efficacy of omeprazole (delayed-release capsules) have been established for the
treatment of symptomatic gastroesophageal reflux disease (GERD), erosive esophagitis, and
maintenance of healing of erosive esophagitis in pediatric patients 2-16 years of age.1, 198 Use in
pediatric patients is supported by adequate and well-controlled studies in adults and additional
pharmacokinetic data and clinical and safety studies in children.1, 198 (See Gastroesophageal
Reflux: Clinical Trials and see Gastroesophageal Reflux: Maintenance Therapy, in Uses.) Safety
of omeprazole delayed-release capsules was assessed in 310 pediatric patients 0-16 years of age
with acid-related disease and in 62 healthy children 2-16 years of age.1, 198 After 3 months of
treatment, about 15% of the pediatric patients with documented healing of erosive esophagitis
continued on maintenance therapy for up to 749 days.1, 198
Safety and efficacy of omeprazole in children younger than 2 years of age have not been
established.1, 198 Safety and efficacy of omeprazole for self-medication in those younger than 18
years of age have not been established.187 Safety and efficacy of omeprazole oral suspension
(Zegerid) have not been established in pediatric patients.207
Geriatric Precautions
In US and European clinical trials, more than 2000 patients treated with omeprazole were 65
years of age or older.1, 207 Although no overall differences in efficacy or safety were observed
between geriatric and younger patients, and other clinical experience revealed no evidence of
age-related differences, the possibility that some older patients may exhibit increased sensitivity
to the drug cannot be ruled out.1, 207
Although elimination of omeprazole may be somewhat delayed and oral bioavailability increased
in the elderly, clinically important differences in the pharmacokinetic profile of omeprazole
between geriatric individuals and younger adults generally do not appear to exist.1, 26, 207
Therefore, dosage adjustment solely on the basis of age generally is not required for geriatric
patients.1, 26, 207
The adverse effect profile of omeprazole is similar in geriatric patients and those 65 years of age
and younger.1, 207
Mutagenicity and Carcinogenicity
No evidence of mutagenicity was observed in vivo in the rat liver DNA damage assay or in some
in vitro test systems, including the microbial (Ames test) and mammalian (mouse lymphoma)
assays.1, 2 207 Omeprazole was positive for clastogenic effects in an in vitro human lymphocyte
chromosome aberration assay, in 1 of 2 in vivo mouse micronucleus tests, and in an in vivo bone
marrow cell chromosomal aberration assay.1, 207
In animals, long-term administration of relatively high dosages of omeprazole results in
morphologic changes in the gastric mucosa.1, 2, 3, 8, 207 Such changes observed in rats during
long-term (24-month) administration of the drug include dose-related increases in gastric
carcinoid tumors and enterochromaffin-like (ECL) cell hyperplasia, which are thought to
represent exaggerated physiologic responses occurring secondary to profound inhibition of
gastric acid secretion and subsequent hypergastrinemia and reversible hypertrophy of oxyntic
mucosa.1, 2, 3, 8, 207 While such changes have not been observed following short-term
22

administration of the drug in humans,1, 2, 3, 8 additional long-term data are needed to rule out the
possibility of an increased risk of gastric tumors in patients receiving long-term omeprazole
therapy.1, 97 In two 24-month studies in rats given omeprazole dosages of 1.7, 3.4, 13.8, 44, and
140.8 mg/kg daily (about 0.7-57 times the human dosage of 20 mg daily based on body surface
area), the drug caused a dose-related increase in gastric ECL cell carcinoids in both male and
female rats; the increase in carcinoids occurred more frequently in female rats.1, 207 In addition,
ECL cell hyperplasia was observed in both male and female rats receiving omeprazole.1, 207 In
female rats given omeprazole dosages of 13.8 mg/kg daily (about 6 times the human dosage of
20 mg daily based on body surface area) for 1 year and then observed for another year without
the drug, carcinoids were not detected but ECL hyperplasia occurred in 94% of rats given
omeprazole versus 10% of controls at the end of 1 year; at the end of the second year,
hyperplasia was observed in 46% of rats given omeprazole versus 26% of controls.1, 207 Gastric
adenocarcinoma was reported in one rat; similar tumors were not seen in male or female rats
treated for 2 years.1 For this strain of rat no similar tumor had been noted historically, but the
finding of this tumor in only one rat is difficult to interpret.1, 207 In a 1-year toxicity study in
Sprague-Dawley rats, brain astrocytomas were found in a small number of males (but not in
females) given omeprazole at dosage levels of 0.4, 2, and 16 mg/kg daily (about 0.2-6.5 times
the human dosage of 20 mg daily based on body surface area).1, 207 In a 2-year carcinogenicity
study in Sprague-Dawley rats, no astrocytomas were found in males or females at 140.8 mg/kg
daily (about 57 times the human dosage of 20 mg daily based on body surface area). 1, 207 Longterm carcinogenicity studies (78 weeks) in mice did not demonstrate increased tumor occurrence;
however, the manufacturer states that the study was inconclusive.1, 207 The drug was not
carcinogenic in a 26-week p53 transgenic mouse study.1, 207
A number of patients with Zollinger-Ellison syndrome receiving long-term therapy with
omeprazole have developed gastric carcinoids; however, Zollinger-Ellison syndrome is known to
be associated with such tumors, and these findings are believed to be related to the underlying
disease rather than to omeprazole therapy.1 Gastric corpus biopsy specimens obtained from more
than 3000 patients in long-term studies with omeprazole have demonstrated an increased
frequency of ECL cell hyperplasia (including micronodular hyperplasia of argyrophil cells) in
association with increased plasma gastrin concentrations and progression to subatrophic or
atrophic gastritis.1, 97, 98, 207 However, no evidence of ECL cell carcinoids, dysplasia, or neoplasia
has been observed in these patients,1, 97, 207 and it has been suggested that the development of
mucosal cell hyperplasia may be related to the severity and natural progression of gastritis rather
than to hypergastrinemia.98
Pregnancy, Fertility, and Lactation
Pregnancy
Omeprazole crosses the placenta in animals and in humans.202, 209 Reproductive studies in rats or
rabbits using omeprazole dosages up to 138 or 69 mg/kg daily (about 56 times the human dosage
of 20 mg daily based on body surface area), respectively, have not revealed evidence of
teratogenicity.1, 202, 207 However, in rabbits given omeprazole dosages of 6.9-69.1 mg/kg daily
(about 5.6-56 times the human dosage of 20 mg daily based on body surface area), dose-related
increases in embryolethality, fetal resorptions, and pregnancy disruptions occurred.1, 202, 207 In
rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in
offspring resulting from administration of omeprazole in dosages of 13.8-138 mg/kg daily (about
5.6-56 times the human dosage of 20 mg daily based on body surface area) to parents.1, 207
23

There are no adequate and controlled studies using omeprazole in pregnant women.1, 207 Most
reported experience with omeprazole during human pregnancy has been first trimester exposure;
duration of use (i.e., intermittent, long-term) rarely has been specified.1, 207 A review of
published data (considered fair in quality and quantity) by the Teratogen Information System
(TERIS) concluded that therapeutic dosages of omeprazole during pregnancy are unlikely to
pose a substantial teratogenic risk.1, 207 Data from cohort studies have not demonstrated that
omeprazole exposure is associated with a statistically significant increase in the rate of major
birth defects; however, the studies lacked the power to detect small increases in birth defects or
in rare malformations.202 Therefore, additional study is needed.202
A population-based retrospective cohort epidemiologic study using data from the Swedish
Medical Birth Registry reported on outcomes in infants whose mothers used omeprazole during
pregnancy; most (about 86%) were exposed to omeprazole during the first trimester, 4% during
and beyond the first trimester, and about 10% were exposed only after the first trimester of
pregnancy.1, 203, 207 Exposure to omeprazole was not associated with increased risk of any
malformation (odds ratio 0.82 and 95% confidence interval of 0.50-1.34), low birth weight, or
low Apgar score.1, 203, 207 The number of infants born with ventricular septal defects and the
number of stillborn infants was slightly higher in the omeprazole-exposed infants than the
expected number in the normal population, but both effects may be random.1, 203, 207 In an earlier
study using data from the Swedish Medical Birth Registry, exposure to proton-pump inhibitors
was not associated with increased risk of congenital malformation.202, 206
In a retrospective cohort study, the incidence of congenital malformations in women who
received omeprazole or histamine H2-antagonists (cimetidine or ranitidine) in the first trimester
of pregnancy was compared with a control group of women who were not exposed to acidsuppressant drugs.1, 202, 204, 207 The overall malformation rate was 4.4% (95% confidence interval
of 3.6-5.3), the malformation rate for nonexposed women was 3.8% (95% confidence interval of
3-4.9), and the malformation rate associated with omeprazole exposure was 3.6% (95%
confidence interval of 1.5-8.1).1, 204, 207 The relative risk of malformations associated with firsttrimester exposure to omeprazole (compared with nonexposed women) was 0.9 (95% confidence
interval of 0.3-2.2).1, 202, 204, 207 The study could effectively rule out a relative risk greater than
2.5 for all malformations.1, 204, 207 Rates of preterm delivery or growth retardation did not differ
between the groups.1, 204, 207
A controlled prospective observational study followed women exposed to omeprazole, diseasepaired controls exposed to histamine H2-receptor antagonists, and controls exposed to
nonteratogenic agents (e.g., acetaminophen, dental radiation) during pregnancy;205 major
congenital malformations occurred in 4, 2.8, and 2%, respectively, of live births, 1, 205, 207 or in
5.1%, 3.1%, and 3%, respectively, of live births when exposure occurred during the first
trimester of pregnancy.202, 205 Rates of spontaneous and elective abortions, preterm deliveries,
gestational age at delivery, and mean birth weight did not differ between the groups.1, 205, 207 The
study lacked statistical power to detect a small increase in major malformations;202, 205 the
sample size had 80% power to detect a fivefold increase in the major malformation rate.1, 204, 207
The manufacturers state that several studies reported that adverse short-term effects were not
observed in infants when a single oral or IV dose of omeprazole was administered to pregnant
women as premedication for cesarean section under general anesthesia.1, 207
24

Omeprazole oral suspension contains sodium bicarbonate; chronic use of sodium bicarbonate
may lead to systemic alkalosis, and increased sodium intake may produce edema and weight
increase.207
Because there are no adequate and controlled studies using omeprazole in pregnant women, and
because studies to date in animals and pregnant women cannot rule out the possibility of harm,
the drug should be used during pregnancy only when the potential benefits justify the possible
risk to the fetus.1, 202, 207
Fertility
Reproductive studies in rats using omeprazole dosages of up to 138 mg/kg daily (about 56 times
the human dose of 20 mg daily based on body surface area) have not revealed evidence of
impaired fertility.1, 207
Lactation
Omeprazole is distributed into human milk;1, 202, 207, 210 following oral administration of
omeprazole 20 mg in one lactating woman, the peak concentration of the drug in breast milk was
less than 7% of the peak serum concentration.1, 139, 207 Because of the potential for serious
adverse reactions to omeprazole in nursing infants, and because of the potential for
tumorigenicity shown in animal studies, a decision should be made whether to discontinue
nursing or the drug, taking account the importance of the drug to the woman.1, 139, 204 Also,
omeprazole oral suspension contains sodium bicarbonate, which should be used with caution in
nursing mothers.207
Description
Omeprazole is a substituted benzimidazole gastric antisecretory agent.1, 2, 3, 4, 5, 207, 208
Omeprazole is structurally and pharmacologically related to esomeprazole, lansoprazole,
pantoprazole, and rabeprazole.1, 5, 103, 104, 139, 140, 141, 142, 207, 208 Omeprazole is a racemic mixture
of R- and S-isomers; esomeprazole is the S-isomer of omeprazole.139, 141, 142 The drugs are
chemically and pharmacologically unrelated to H2-receptor antagonists, antimuscarinics, or
prostaglandin analogs.1, 2, 3, 4, 5, 207, 208
Because the omeprazole molecule is acid labile, the drug is administered orally as a delayedrelease capsule, delayed-release tablet, or buffered oral suspension.1, 187, 207, 208 The
commercially available omeprazole delayed-release capsules increase oral bioavailability by
delaying absorption until after the capsule leaves the stomach; peak plasma concentrations of
omeprazole occur 30 minutes to 3.5 hours after administration.1 Omeprazole oral suspension is a
rapidly absorbed immediate-release formulation of the drug that contains sodium bicarbonate to
neutralize gastric acid; mean peak plasma concentrations of the drug occur at about 30 minutes
(range 10-90 minutes) after oral administration of the suspension on an empty stomach (1 hour
prior to a meal).207, 208
Omeprazole binds to hydrogen/potassium adenosine triphosphatase (H+K+-exchanging ATPase)
in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen,
or acid pump) blocks the final step in the secretion of hydrochloric acid by these cells.1, 2, 3, 4, 5, 8,
132, 207, 208
Therefore, gastric antisecretory agents such as omeprazole and lansoprazole are
25

commonly referred to as acid- or proton-pump inhibitors.1, 2, 3, 4, 5, 8, 132, 207, 208 Omeprazole, a


weak base, does not directly inhibit this enzyme system, but instead, it concentrates under the
acid conditions of the parietal cell secretory canaliculi, where the drug undergoes rearrangement
to its active sulfenamide metabolite; this metabolite then reacts with sulfhydryl groups of H+K+exchanging ATPase, inactivating the proton pump.2, 3, 5, 132 Because the sulfenamide metabolite
forms an irreversible covalent bond to H+K+-exchanging ATPase, acid secretion is inhibited until
additional enzyme is synthesized, resulting in a prolonged duration of action.2, 3, 5, 8, 132 In an
animal model, the pharmacologic effect of the drug at this enzyme was shown to correlate
directly with sulfenamide formation.2
Omeprazole inhibits basal and stimulated gastric acid secretion; in addition, because the drug
inhibits the final step in the secretory pathway, it inhibits such secretion regardless of the
stimulus.1, 2, 3, 4, 5, 207, 208 The degree of inhibition of gastric acid secretion is related to the dose
and duration of therapy, but omeprazole is a more potent inhibitor of such secretion than are H2receptor antagonists.1, 2, 3, 4, 5, 207, 208 Following oral administration of omeprazole, inhibition of
gastric acid secretion is apparent within 1 hour, peaks within 2 hours, and persists for up to 72
hours.1, 2, 3 Inhibition of gastric acid secretion increases with continuous drug administration and
reaches a plateau after about 4 days of omeprazole therapy.1, 3 Although omeprazole has a short
terminal plasma half-life, the drug has a long duration of action (presumably secondary to
prolonged binding of the drug to H+K+-exchanging ATPase).1, 207 Following continuous oral
administration of omeprazole, 78 and 58-80% of basal gastric acid secretion is inhibited 2-6 and
24 hours, respectively, after a 20-mg dose, and 94 and 80-93% of basal gastric acid secretion is
inhibited, respectively, after a 40-mg dose.1 Following continuous oral administration, 79 and
50-59% of peak gastric acid output is inhibited 2-6 and 24 hours, respectively, after a 20-mg
dose, and 88 and 62-68% of peak gastric acid output is inhibited, respectively, after a 40-mg
dose.1 Oral administration of omeprazole 10-40 mg daily has reduced 24-hour intragastric acidity
by 100% in some patients.1, 4, 207 Following discontinuance of omeprazole therapy, gastric acid
secretion returns to baseline over a 3-5 day period.1
Following oral administration of omeprazole 20 or 40 mg daily (as the oral suspension) in
healthy individuals, the median decrease in 24-hour integrated gastric acidity from baseline was
82 or 84%, respectively, the percent of time during a 24-hour period that the gastric pH exceeded
4 was 51 or 77%, respectively, and the median 24-hour gastric pH was 4.2 or 5.2,
respectively.207, 208 In critically ill patients receiving omeprazole 40 mg daily as the oral
suspension via nasogastric or orogastric tube, the median daily gastric pH was above 4 in at least
95% of patients over the course of a 14-day trial.207, 208 Gastric pH was above 4 in 99% of
patients 1-2.5 hours after the first dose, and in 92% of patients 6 hours after the first dose.207, 208
Omeprazole increases plasma gastrin concentrations; this increase occurs via a negative feedback
mechanism resulting from decreased gastric acid secretion.1, 2, 3, 8, 207 Because of omeprazole's
greater potency as an inhibitor of gastric acid secretion, the drug also causes secondary increases
in plasma gastrin concentrations that exceed those produced by H2-receptor antagonists.1, 2, 207
For example, administration of omeprazole 20 mg once daily for 1-2 weeks results in a 1.3- to
3.6-fold increase in plasma gastrin concentration, whereas administration of an H2-receptor
antagonist usually results in only a 1.1- to 1.8-fold increase.1, 207 Plasma gastrin concentrations
return to pretreatment values with 1-4 weeks after discontinuing omeprazole therapy.1, 2, 207
Despite omeprazole-induced reductions in gastric acid secretion, the drug does not contribute
26

appreciably to increased plasma gastrin concentrations in most patients with Zollinger-Ellison


syndrome,1, 2, 13 since gastrin is produced principally by the tumor rather than in response to
achlorhydria in such patients.13 Omeprazole also indirectly causes a dose-dependent reduction in
pepsin secretion by decreasing the volume of gastric acid secretion.1, 4, 8 A systematic dosedependent effect on basal or stimulated pepsin secretion has not been observed in humans; basal
pepsin output is low and pepsin activity is decreased when intragastric pH is maintained above
4.1, 207 The drug does not appear to affect intrinsic factor secretion.1, 2, 8, 207
Omeprazole can suppress gastric Helicobacter pylori (formerly Campylobacter pylori or C.
pyloridis) in patients with duodenal ulcer and/or reflux esophagitis infected with the organism.2
Combined therapy with omeprazole and one or more appropriate anti-infectives (e.g.,
clarithromycin, amoxicillin), can effectively eradicate H. pylori gastric infection.1, 2, 67, 98, 138
(See Duodenal Ulcer: Acute Therapy, in Uses.) Omeprazole does not appear to affect gastric
emptying1, 8 or lower esophageal sphincter pressure.4, 8
Short-term administration (2-4 weeks) of omeprazole dosages of 30-40 mg daily does not appear
to affect thyroid function, carbohydrate metabolism, or plasma/serum concentrations of
parathyroid hormone (parathormone), cortisol, estradiol, testosterone, prolactin, cholecystokinin,
or secretin.1, 2 However, the drug may decrease antral somatostatin concentrations.2
Long-term therapy with proton-pump inhibitors has been associated with an increased risk of hip
fracture in individuals older than 50 years of age.212 (See Cautions: Musculoskeletal Effects.)
The mechanism by which these drugs may increase risk of such fractures has not been elucidated
but may involve decreased insoluble calcium absorption secondary to increased gastric pH.212
Additional Information
SumMon (see Users Guide). For additional information on this drug until a more detailed
monograph is developed and published, the manufacturer's labeling should be consulted. It is
essential that the labeling be consulted for detailed information on the usual cautions,
precautions, and contraindications concerning potential drug interactions and/or laboratory test
interferences and for information on acute toxicity.
Preparations
* available generically
Omeprazole
Routes Dosage Forms Strengths Brand Names Manufacturer Oral Capsules, delayed- 10 mg*
Omeprazole Delayed-release Apotex, Kremers release Capsules Urban, Lek, Mylan
(containing enteric- coated granules) Prilosec AstraZeneca 20 mg Omeprazole Delayedrelease Apotex, Kremers Capsules Urban, Lek, Mylan, Teva, UDL Prilosec AstraZeneca 40
mg Prilosec AstraZeneca For suspension, 20 mg/ Zegerid (with sodium Santarus powder
packet bicarbonate) 40 mg/ Zegerid (with sodium Santarus packet bicarbonate)
Omeprazole Magnesium
Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablets, delayed- 20 mg (of
Prilosec OTC Procter & Gamble release omeprazole)
27

Comparative Pricing
Pricing information provided by drugstore.com.
Omeprazole 10MG CPDR (KREMERS URBAN): 90/$81.98 or 180/$156.91
Omeprazole 20MG CPDR (MYLAN): 90/$63.97 or 180/$119.93
Prilosec 10MG CPDR (ASTRAZENECA LP): 30/$114.99 or 90/$319.97
Prilosec 20MG CPDR (ASTRAZENECA LP): 30/$136.99 or 90/$389.95
Prilosec 40MG CPDR (ASTRAZENECA LP): 30/$207.98 or 90/$568.89
Prilosec OTC 20MG TBEC (P & G HEALTH): 14/$19.99 or 42/$39.97
Zegerid 40-1100MG CAPS (SANTARUS): 30/$127.05 or 90/$346.93
AHFS Drug Information. Copyright, 1959-2008, Selected Revisions January 2008. American
Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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