PRILOSEC

PRILOSEC is supplied as delayed-release capsules for oral administration. Each delayed-release capsule contains either 10 mg, 20 mg or 40 mg of omeprazole in the form of enteric-coated granules with the following inactive ingredients: cellulose, disodium hydrogen phosphate, hydroxypropyl cellulose, hypromellose, lactose, mannitol, sodium lauryl sulfate and other ingredients. The capsule shells have the following inactive ingredients: gelatin-NF, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, synthetic black iron oxide, isopropanol, butyl alcohol, FD&C Blue #2, D&C Red #7 Calcium Lake, and, in addition, the 10 mg and 40 mg capsule shells also contain D&C Yellow #10.

Each packet of PRILOSEC For Delayed-Release Oral Suspension contains either 2.8 mg or 11.2 mg of omeprazole magnesium (equivalent to 2.5 mg or 10 mg of omeprazole), in the form of enteric-coated granules with the following inactive ingredients: glyceryl monostearate, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer C, polysorbate, sugar spheres, talc, and triethyl citrate, and also inactive granules. The inactive granules are composed of the following ingredients: citric acid, crospovidone, dextrose, hydroxypropyl cellulose, iron oxide and xantham gum. The omeprazole granules and inactive granules are constituted with water to form a suspension and are given by oral, nasogastric or direct gastric administration.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H⁺/K⁺ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. Animal studies indicate that after rapid disappearance from plasma, omeprazole can be found within the gastric mucosa for a day or more.

12.2 Pharmacodynamics

Antisecretory Activity

After oral administration, the onset of the antisecretory effect of omeprazole occurs within one hour, with the maximum effect occurring within two hours. Inhibition of secretion is about 50% of maximum at 24 hours and the duration of inhibition lasts up to 72 hours. The antisecretory effect thus lasts far longer than would be expected from the very short (less than one hour) plasma half-life, apparently due to prolonged binding to the parietal H⁺/K⁺ ATPase enzyme. When the drug is discontinued, secretory activity returns gradually, over 3 to 5 days. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days.

Results from numerous studies of the antisecretory effect of multiple doses of 20 mg and 40 mg of omeprazole in normal volunteers and patients are shown below. The “max” value represents determinations at a time of maximum effect (2-6 hours after dosing), while “min” values are those 24 hours after the last dose of omeprazole.

Single daily oral doses of omeprazole ranging from a dose of 10 mg to 40 mg have produced 100% inhibition of 24-hour intragastric acidity in some patients.

Serum Gastrin Effects

In studies involving more than 200 patients, serum gastrin levels increased during the first 1 to 2 weeks of once-daily administration of therapeutic doses of omeprazole in parallel with inhibition of acid secretion. No further increase in serum gastrin occurred with continued treatment. In comparison with histamine H₂-receptor antagonists, the median increases produced by 20 mg doses of omeprazole were higher (1.3 to 3.6 fold vs. 1.1 to 1.8 fold increase). Gastrin values returned to pretreatment levels, usually within 1 to 2 weeks after discontinuation of therapy.

Increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum Chromogranin A (CgA) levels. The increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop omeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high.

Enterochromaffin-like (ECL) Cell Effects

Human gastric biopsy specimens have been obtained from more than 3000 patients (both children and adults) treated with omeprazole in long-term clinical trials. The incidence of ECL cell hyperplasia in these studies increased with time; however, no case of ECL cell carcinoids, dysplasia, or neoplasia has been found in these patients [see Clinical Pharmacology (12) ]. However, these studies are of insufficient duration and size to rule out the possible influence of long-term administration of omeprazole on the development of any premalignant or malignant conditions.

Other Effects

Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found to date. Omeprazole, given in oral doses of 30 or 40 mg for 2 to 4 weeks, had no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estradiol, testosterone, prolactin, cholecystokinin or secretin.

No effect on gastric emptying of the solid and liquid components of a test meal was demonstrated after a single dose of omeprazole 90 mg. In healthy subjects, a single I.V. dose of omeprazole (0.35 mg/kg) had no effect on intrinsic factor secretion. No systematic dose-dependent effect has been observed on basal or stimulated pepsin output in humans.

However, when intragastric pH is maintained at 4.0 or above, basal pepsin output is low, and pepsin activity is decreased.

As do other agents that elevate intragastric pH, omeprazole administered for 14 days in healthy subjects produced a significant increase in the intragastric concentrations of viable bacteria. The pattern of the bacterial species was unchanged from that commonly found in saliva. All changes resolved within three days of stopping treatment.

The course of Barrett’s esophagus in 106 patients was evaluated in a U.S. double-blind controlled study of PRILOSEC 40 mg twice daily for 12 months followed by 20 mg twice daily for 12 months or ranitidine 300 mg twice daily for 24 months. No clinically significant impact on Barrett’s mucosa by antisecretory therapy was observed. Although neosquamous epithelium developed during antisecretory therapy, complete elimination of Barrett’s mucosa was not achieved. No significant difference was observed between treatment groups in development of dysplasia in Barrett’s mucosa and no patient developed esophageal carcinoma during treatment. No significant differences between treatment groups were observed in development of ECL cell hyperplasia, corpus atrophic gastritis, corpus intestinal metaplasia, or colon polyps exceeding 3 mm in diameter [see Clinical Pharmacology (12) ].

12.3 Pharmacokinetics

Absorption

PRILOSEC Delayed-Release Capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid-labile), so that absorption of omeprazole begins only after the granules leave the stomach. Absorption is rapid, with peak plasma levels of omeprazole occurring within 0.5 to 3.5 hours. Peak plasma concentrations of omeprazole and AUC are approximately proportional to doses up to 40 mg, but because of a saturable first-pass effect, a greater than linear response in peak plasma concentration and AUC occurs with doses greater than 40 mg. Absolute bioavailability (compared with intravenous administration) is about 30-40% at doses of 20-40 mg, due in large part to presystemic metabolism. In healthy subjects the plasma half-life is 0.5 to 1 hour, and the total body clearance is 500-600 mL/min.

Based on a relative bioavailability study, the AUC and C_max of PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension were 87% and 88% of those for PRILOSEC Delayed-Release Capsules, respectively.

The bioavailability of omeprazole increases slightly upon repeated administration of PRILOSEC Delayed-Release Capsules.

PRILOSEC Delayed-Release Capsule 40 mg was bioequivalent when administered with and without applesauce. However, PRILOSEC Delayed-Release Capsule 20 mg was not bioequivalent when administered with and without applesauce. When administered with applesauce, a mean 25% reduction in C_max was observed without a significant change in AUC for PRILOSEC Delayed-Release Capsule 20 mg. The clinical relevance of this finding is unknown.

Distribution

Protein binding is approximately 95%.

Metabolism

Omeprazole is extensively metabolized by the cytochrome P450 (CYP) enzyme system.

Excretion

Following single dose oral administration of a buffered solution of omeprazole, little if any unchanged drug was excreted in urine. The majority of the dose (about 77%) was eliminated in urine as at least six metabolites. Two were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was recoverable in feces. This implies a significant biliary excretion of the metabolites of omeprazole. Three metabolites have been identified in plasma - the sulfide and sulfone derivatives of omeprazole, and hydroxyomeprazole. These metabolites have very little or no antisecretory activity.

Combination Therapy with Antimicrobials

Omeprazole 40 mg daily was given in combination with clarithromycin 500 mg every 8 hours to healthy adult male subjects. The steady state plasma concentrations of omeprazole were increased (C_max, AUC_0-24, and T_1/2 increases of 30%, 89% and 34% respectively) by the concomitant administration of clarithromycin. The observed increases in omeprazole plasma concentration were associated with the following pharmacological effects. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when co-administered with clarithromycin.

The plasma levels of clarithromycin and 14-hydroxy-clarithromycin were increased by the concomitant administration of omeprazole. For clarithromycin, the mean C_max was 10% greater, the mean C_min was 27% greater, and the mean AUC_0-8 was 15% greater when clarithromycin was administered with omeprazole than when clarithromycin was administered alone. Similar results were seen for 14-hydroxy-clarithromycin, the mean C_max was 45% greater, the mean C_min was 57% greater, and the mean AUC_0-8 was 45% greater. Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.

Table 2 Clarithromycin Tissue Concentrations 2 hours after DoseMean ± SD (μg/g)

Tissue	Clarithromycin	Clarithromycin + Omeprazole
Antrum	10.48 ± 2.01 (n = 5)	19.96 ± 4.71 (n = 5)
Fundus	20.81 ± 7.64 (n = 5)	24.25 ± 6.37 (n = 5)
Mucus	4.15 ± 7.74 (n = 4)	39.29 ± 32.79 (n = 4)

Concomitant Use with Clopidogrel

In a crossover clinical study, 72 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with omeprazole (80 mg at the same time as clopidogrel) for 5 days. The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole were administered together.

Results from another crossover study in healthy subjects showed a similar pharmacokinetic interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole 80 mg daily when co-administered for 30 days. Exposure to the active metabolite of clopidogrel was reduced by 41% to 46% over this time period.

In another study, 72 healthy subjects were given the same doses of clopidogrel and 80 mg omeprazole but the drugs were administered 12 hours apart; the results were similar, indicating that administering clopidogrel and omeprazole at different times does not prevent their interaction.

Special Populations

Geriatric Population

The elimination rate of omeprazole was somewhat decreased in the elderly, and bioavailability was increased. Omeprazole was 76% bioavailable when a single 40 mg oral dose of omeprazole (buffered solution) was administered to healthy elderly volunteers, versus 58% in young volunteers given the same dose. Nearly 70% of the dose was recovered in urine as metabolites of omeprazole and no unchanged drug was detected. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers.

Pediatric Use

The pharmacokinetics of omeprazole have been investigated in pediatric patients 2 to 16 years of age:

Following comparable mg/kg doses of omeprazole, younger children (2 to 5 years of age) have lower AUCs than children 6 to 16 years of age or adults; AUCs of the latter two groups did not differ [see Dosage and Administration (2) ].

Hepatic Impairment

In patients with chronic hepatic disease, the bioavailability increased to approximately 100% compared with an I.V. dose, reflecting decreased first-pass effect, and the plasma half-life of the drug increased to nearly 3 hours compared with the half-life in normals of 0.5-1 hour. Plasma clearance averaged 70 mL/min, compared with a value of 500-600 mL/min in normal subjects. Dose reduction, particularly where maintenance of healing of erosive esophagitis is indicated, for the hepatically impaired should be considered.

Renal Impairment

In patients with chronic renal impairment, whose creatinine clearance ranged between 10 and 62 mL/min/1.73 m², the disposition of omeprazole was very similar to that in healthy volunteers, although there was a slight increase in bioavailability. Because urinary excretion is a primary route of excretion of omeprazole metabolites, their elimination slowed in proportion to the decreased creatinine clearance. No dose reduction is necessary in patients with renal impairment.

Asian Population

In pharmacokinetic studies of single 20 mg omeprazole doses, an increase in AUC of approximately four-fold was noted in Asian subjects compared with Caucasians. Dose reduction, particularly where maintenance of healing of erosive esophagitis is indicated, for Asian subjects should be considered.

12.4 Microbiology

Omeprazole and clarithromycin dual therapy and omeprazole, clarithromycin and amoxicillin triple therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections as described in the Indications and Usage section (1.1).

Helicobacter

Helicobacter pylori- Pretreatment Resistance

Clarithromycin pretreatment resistance rates were 3.5% (4/113) in the omeprazole/clarithromycin dual therapy studies (4 and 5) and 9.3% (41/439) in omeprazole/clarithromycin/amoxicillin triple therapy studies (1, 2, and 3).

Amoxicillin pretreatment susceptible isolates (≤ 0.25 µg/mL) were found in 99.3% (436/439) of the patients in the omeprazole/clarithromycin/amoxicillin triple therapy studies (1, 2, and 3). Amoxicillin pretreatment minimum inhibitory concentrations (MICs) > 0.25 µg/mL occurred in 0.7% (3/439) of the patients, all of whom were in the clarithromycin and amoxicillin study arm. One patient had an unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of > 256 µg/mL by Etest^®.

Patients not eradicated of H. pylori following omeprazole/clarithromycin/amoxicillin triple therapy or omeprazole/clarithromycin dual therapy will likely have clarithromycin resistant H. pylori isolates. Therefore, clarithromycin susceptibility testing should be done, if possible. Patients with clarithromycin resistant H. pylori should not be treated with any of the following: omeprazole/clarithromycin dual therapy, omeprazole/clarithromycin/amoxicillin triple therapy, or other regimens which include clarithromycin as the sole antimicrobial agent.

Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes

In the triple therapy clinical trials, 84.9% (157/185) of the patients in the omeprazole/clarithromycin/amoxicillin treatment group who had pretreatment amoxicillin susceptible MICs (≤ 0.25 µg/mL) were eradicated of H. pylori and 15.1% (28/185) failed therapy. Of the 28 patients who failed triple therapy, 11 had no post-treatment susceptibility test results and 17 had post-treatment H. pylori isolates with amoxicillin susceptible MICs. Eleven of the patients who failed triple therapy also had post-treatment H. pylori isolates with clarithromycin resistant MICs.

Susceptibility Test for Helicobacter pylori

For susceptibility testing information about Helicobacter pylori, see Microbiology section in prescribing information for clarithromycin and amoxicillin.

Effects on Gastrointestinal Microbial Ecology

Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter and, in hospitalized patients, possibly also Clostridium difficile.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (about 0.35 to 28 times a human dose of 40 mg/day, as expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 2.8 times a human dose of 40 mg/day, based on body surface area) for one year, and then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of one year (94% treated vs 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for two years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. In a 52-week toxicity study in Sprague-Dawley rats, brain astrocytomas were found in a small number of males that received omeprazole at dose levels of 0.4, 2, and 16 mg/kg/day (about 0.1 to 3.2 times the human dose of 40 mg/day, based on a body surface area basis). No astrocytomas were observed in female rats in this study. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found in males or females at the high dose of 140.8 mg/kg/day (about 28 times the human dose of 40 mg/day on a body surface area basis). A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive.

Omeprazole was positive for clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration assay. Omeprazole was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay.

Omeprazole at oral doses up to 138 mg/kg/day in rats (about 28 times an oral human dose of 40 mg on a body surface area basis) was found to have no effect on fertility and reproductive performance.

In 24-month carcinogenicity studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals [see Warnings and Precautions (5) ]. Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H₂-receptor antagonists.

13.2 Animal Toxicology and/or Pharmacology

Reproduction Studies

Reproductive Toxicology Studies

Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 28 times the human dose of 40 mg/day on a body surface area basis) and in rabbits at doses up to 69 mg/kg/day (about 28 times the human dose on a body surface area basis) did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 2.8 to 28 times the human dose of 40 mg/day on a body surface area basis) produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 2.8 to 28 times the human dose of 40 mg/day on a body surface area basis) [see Pregnancy, Animal Data (8.1) ]. 

Juvenile Animal Study

A 28-day toxicity study with a 14-day recovery phase was conducted in juvenile rats with esomeprazole magnesium at doses of 70 to 280 mg/kg/day (about 17 to 57 times a daily oral human dose of 40 mg on a body surface area basis). An increase in the number of deaths at the high dose of 280 mg/kg/day was observed when juvenile rats were administered esomeprazole magnesium from postnatal day 7 through postnatal day 35. In addition, doses equal to or greater than 140 mg/kg/day (about 34 times a daily oral human dose of 40 mg on a body surface area basis), produced treatment-related decreases in body weight (approximately 14%) and body weight gain, decreases in femur weight and femur length, and affected overall growth. Comparable findings described above have also been observed in this study with another esomeprazole salt, esomeprazole strontium, at equimolar doses of esomeprazole.

14 CLINICAL STUDIES

14.1 Duodenal Ulcer Disease

Active Duodenal Ulcer— In a multicenter, double-blind, placebo-controlled study of 147 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 2 and 4 weeks was significantly higher with PRILOSEC 20 mg once daily than with placebo (p ≤ 0.01).

Complete daytime and nighttime pain relief occurred significantly faster (p ≤ 0.01) in patients treated with PRILOSEC 20 mg than in patients treated with placebo. At the end of the study, significantly more patients who had received PRILOSEC had complete relief of daytime pain (p ≤ 0.05) and nighttime pain (p ≤ 0.01).

In a multicenter, double-blind study of 293 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 4 weeks was significantly higher with PRILOSEC 20 mg once daily than with ranitidine 150 mg b.i.d. (p < 0.01).

Healing occurred significantly faster in patients treated with PRILOSEC than in those treated with ranitidine 150 mg b.i.d. (p < 0.01).

In a foreign multinational randomized, double-blind study of 105 patients with endoscopically documented duodenal ulcer, 20 mg and 40 mg of PRILOSEC were compared with 150 mg b.i.d. of ranitidine at 2, 4 and 8 weeks. At 2 and 4 weeks both doses of PRILOSEC were statistically superior (per protocol) to ranitidine, but 40 mg was not superior to 20 mg of PRILOSEC, and at 8 weeks there was no significant difference between any of the active drugs.

H. pylori Eradication in Patients with Duodenal Ulcer Disease

Triple Therapy(PRILOSEC/clarithromycin/amoxicillin) — Three U.S., randomized, double-blind clinical studies in patients with H. pylori infection and duodenal ulcer disease (n = 558) compared PRILOSEC plus clarithromycin plus amoxicillin with clarithromycin plus amoxicillin. Two studies (1 and 2) were conducted in patients with an active duodenal ulcer, and the other study (3) was conducted in patients with a history of a duodenal ulcer in the past 5 years but without an ulcer present at the time of enrollment. The dose regimen in the studies was PRILOSEC 20 mg twice daily plus clarithromycin 500 mg twice daily plus amoxicillin 1 g twice daily for 10 days; or clarithromycin 500 mg twice daily plus amoxicillin 1 g twice daily for 10 days. In studies 1 and 2, patients who took the omeprazole regimen also received an additional 18 days of PRILOSEC 20 mg once daily. Endpoints studied were eradication of H. pylori and duodenal ulcer healing (studies 1 and 2 only). H. pylori status was determined by CLOtest^®, histology and culture in all three studies. For a given patient, H. pylori was considered eradicated if at least two of these tests were negative, and none was positive.

The combination of omeprazole plus clarithromycin plus amoxicillin was effective in eradicating H. pylori.

Table 5 Per-Protocol and Intent-to-Treat H. pylori Eradication Rates % of Patients Cured [95% Confidence Interval]

	PRILOSEC +clarithromycin +amoxicillin		Clarithromycin +amoxicillin
	Per-Protocol Patients were included in the analysis if they had confirmed duodenal ulcer disease (active ulcer, studies 1 and 2; history of ulcer within 5 years, study 3) and H. pylori infection at baseline defined as at least two of three positive endoscopic tests from CLOtest, histology, and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy. The impact of eradication on ulcer recurrence has not been assessed in patients with a past history of ulcer.	Intent-to-Treat Patients were included in the analysis if they had documented H. pylori infection at baseline and had confirmed duodenal ulcer disease. All dropouts were included as failures of therapy.	Per-Protocol Patients were included in the analysis if they had confirmed duodenal ulcer disease (active ulcer, studies 1 and 2; history of ulcer within 5 years, study 3) and H. pylori infection at baseline defined as at least two of three positive endoscopic tests from CLOtest, histology, and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy. The impact of eradication on ulcer recurrence has not been assessed in patients with a past history of ulcer.	Intent-to-Treat Patients were included in the analysis if they had documented H. pylori infection at baseline and had confirmed duodenal ulcer disease. All dropouts were included as failures of therapy.
Study 1	77(p < 0.05) versus clarithromycin plus amoxicillin. [64, 86] (n = 64)	69(p < 0.05) versus clarithromycin plus amoxicillin. [57, 79] (n = 80)	43 [31, 56] (n = 67)	37 [27, 48] (n = 84)
Study 2	78(p < 0.05) versus clarithromycin plus amoxicillin. [67, 88] (n = 65)	73(p < 0.05) versus clarithromycin plus amoxicillin. [61, 82] (n = 77)	41 [29, 54] (n = 68)	36 [26, 47] (n = 83)
Study 3	90(p < 0.05) versus clarithromycin plus amoxicillin. [80, 96] (n = 69)	83(p < 0.05) versus clarithromycin plus amoxicillin. [74, 91] (n = 84)	33 [24, 44] (n = 93)	32 [23, 42] (n = 99)

Dual Therapy (PRILOSEC/clarithromycin)

Four randomized, double-blind, multi-center studies (4, 5, 6, and 7) evaluated PRILOSEC 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days, followed by PRILOSEC 20 mg once daily, (Studies 4, 5, and 7) or by PRILOSEC 40 mg once daily (Study 6) for an additional 14 days in patients with active duodenal ulcer associated with H. pylori. Studies 4 and 5 were conducted in the U.S. and Canada and enrolled 242 and 256 patients, respectively. H. pylori infection and duodenal ulcer were confirmed in 219 patients in Study 4 and 228 patients in Study 5. These studies compared the combination regimen to PRILOSEC and clarithromycin monotherapies. Studies 6 and 7 were conducted in Europe and enrolled 154 and 215 patients, respectively. H. pylori infection and duodenal ulcer were confirmed in 148 patients in study 6 and 208 patients in Study 7. These studies compared the combination regimen with omeprazole monotherapy. The results for the efficacy analyses for these studies are described below. H. pylori eradication was defined as no positive test (culture or histology) at 4 weeks following the end of treatment, and two negative tests were required to be considered eradicated of H. pylori. In the per-protocol analysis, the following patients were excluded: dropouts, patients with missing H. pylori tests post-treatment, and patients that were not assessed for H. pylori eradication because they were found to have an ulcer at the end of treatment.

The combination of omeprazole and clarithromycin was effective in eradicating H. pylori.

Ulcer healing was not significantly different when clarithromycin was added to omeprazole therapy compared with omeprazole therapy alone.

The combination of omeprazole and clarithromycin was effective in eradicating H. pylori and reduced duodenal ulcer recurrence.

14.2 Gastric Ulcer

In a U.S. multicenter, double-blind, study of omeprazole 40 mg once daily, 20 mg once daily, and placebo in 520 patients with endoscopically diagnosed gastric ulcer, the following results were obtained.

For the stratified groups of patients with ulcer size less than or equal to 1 cm, no difference in healing rates between 40 mg and 20 mg was detected at either 4 or 8 weeks. For patients with ulcer size greater than 1 cm, 40 mg was significantly more effective than 20 mg at 8 weeks.

In a foreign, multinational, double-blind study of 602 patients with endoscopically diagnosed gastric ulcer, omeprazole 40 mg once daily, 20 mg once daily, and ranitidine 150 mg twice a day were evaluated.

14.3 Gastroesophageal Reflux Disease (GERD)

Symptomatic GERD

A placebo-controlled study was conducted in Scandinavia to compare the efficacy of omeprazole 20 mg or 10 mg once daily for up to 4 weeks in the treatment of heartburn and other symptoms in GERD patients without erosive esophagitis. Results are shown below.

% Successful Symptomatic OutcomeDefined as complete resolution of heartburn

	PRILOSEC 20 mg a.m.	PRILOSEC 10 mg a.m.	Placebo a.m.
All patients	46(p < 0.005) versus 10 mg (p < 0l.005) versus placebo (n = 205)	31(p < 0l.005) versus placebo (n = 199)	13 (n = 105)
Patients with confirmed GERD	56(p < 0.005) versus 10 mg (p < 0l.005) versus placebo (n = 115)	36(p < 0l.005) versus placebo (n = 109)	14 (n = 59)

14.4 Erosive Esophagitis

In a U.S. multicenter double-blind placebo controlled study of 20 mg or 40 mg of PRILOSEC Delayed-Release Capsules in patients with symptoms of GERD and endoscopically diagnosed erosive esophagitis of grade 2 or above, the percentage healing rates (per protocol) were as follows:

In this study, the 40 mg dose was not superior to the 20 mg dose of PRILOSEC in the percentage healing rate. Other controlled clinical trials have also shown that PRILOSEC is effective in severe GERD. In comparisons with histamine H₂-receptor antagonists in patients with erosive esophagitis, grade 2 or above, PRILOSEC in a dose of 20 mg was significantly more effective than the active controls. Complete daytime and nighttime heartburn relief occurred significantly faster (p < 0.01) in patients treated with PRILOSEC than in those taking placebo or histamine H₂- receptor antagonists.

In this and five other controlled GERD studies, significantly more patients taking 20 mg omeprazole (84%) reported complete relief of GERD symptoms than patients receiving placebo (12%).

Long Term Maintenance of Healing of Erosive Esophagitis

In a U.S. double-blind, randomized, multicenter, placebo controlled study, two dose regimens of PRILOSEC were studied in patients with endoscopically confirmed healed esophagitis. Results to determine maintenance of healing of erosive esophagitis are shown below.

In an international multicenter double-blind study, PRILOSEC 20 mg daily and 10 mg daily were compared with ranitidine 150 mg twice daily in patients with endoscopically confirmed healed esophagitis. The table below provides the results of this study for maintenance of healing of erosive esophagitis.

In patients who initially had grades 3 or 4 erosive esophagitis, for maintenance after healing 20 mg daily of PRILOSEC was effective, while 10 mg did not demonstrate effectiveness.

14.5 Pathological Hypersecretory Conditions

In open studies of 136 patients with pathological hypersecretory conditions, such as Zollinger-Ellison (ZE) syndrome with or without multiple endocrine adenomas, PRILOSEC Delayed-Release Capsules significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia, and pain. Doses ranging from 20 mg every other day to 360 mg per day maintained basal acid secretion below 10 mEq/hr in patients without prior gastric surgery, and below 5 mEq/hr in patients with prior gastric surgery.

Initial doses were titrated to the individual patient need, and adjustments were necessary with time in some patients [see Dosage and Administration (2) ]. PRILOSEC was well tolerated at these high dose levels for prolonged periods (> 5 years in some patients). In most ZE patients, serum gastrin levels were not modified by PRILOSEC. However, in some patients serum gastrin increased to levels greater than those present prior to initiation of omeprazole therapy. At least 11 patients with ZE syndrome on long-term treatment with PRILOSEC developed gastric carcinoids. These findings are believed to be a manifestation of the underlying condition, which is known to be associated with such tumors, rather than the result of the administration of PRILOSEC [see Adverse Reactions (6) ].

14.6 Pediatric GERD

Symptomatic GERD

The effectiveness of PRILOSEC for the treatment of nonerosive GERD in pediatric patients 1 to 16 years of age is based in part on data obtained from 125 pediatric patients in two uncontrolled Phase III studies [see Use in Specific Populations (8.4) ].

The first study enrolled 12 pediatric patients 1 to 2 years of age with a history of clinically diagnosed GERD. Patients were administered a single dose of omeprazole (0.5 mg/kg, 1.0 mg/kg, or 1.5 mg/kg) for 8 weeks as an open capsule in 8.4% sodium bicarbonate solution. Seventy-five percent (9/12) of the patients had vomiting/regurgitation episodes decreased from baseline by at least 50%.

The second study enrolled 113 pediatric patients 2 to 16 years of age with a history of symptoms suggestive of nonerosive GERD. Patients were administered a single dose of omeprazole (10 mg or 20 mg, based on body weight) for 4 weeks either as an intact capsule or as an open capsule in applesauce. Successful response was defined as no moderate or severe episodes of either pain-related symptoms or vomiting/regurgitation during the last 4 days of treatment. Results showed success rates of 60% (9/15; 10 mg omeprazole) and 59% (58/98; 20 mg omeprazole), respectively.

Healing of Erosive Esophagitis

In an uncontrolled, open-label dose-titration study, healing of erosive esophagitis in pediatric patients 1 to 16 years of age required doses that ranged from 0.7 to 3.5 mg/kg/day (80 mg/day). Doses were initiated at 0.7 mg/kg/day. Doses were increased in increments of 0.7 mg/kg/day (if intraesophageal pH showed a pH of < 4 for less than 6% of a 24-hour study). After titration, patients remained on treatment for 3 months. Forty-four percent of the patients were healed on a dose of 0.7 mg/kg body weight; most of the remaining patients were healed with 1.4 mg/kg after an additional 3 months’ treatment. Erosive esophagitis was healed in 51 of 57 (90%) children who completed the first course of treatment in the healing phase of the study. In addition, after 3 months of treatment, 33% of the children had no overall symptoms, 57% had mild reflux symptoms, and 40% had less frequent regurgitation/vomiting.

Maintenance of Healing of Erosive Esophagitis

In an uncontrolled, open-label study of maintenance of healing of erosive esophagitis in 46 pediatric patients, 54% of patients required half the healing dose. The remaining patients increased the healing dose (0.7 to a maximum of 2.8 mg/kg/day) either for the entire maintenance period, or returned to half the dose before completion. Of the 46 patients who entered the maintenance phase, 19 (41%) had no relapse. In addition, maintenance therapy in erosive esophagitis patients resulted in 63% of patients having no overall symptoms.

15 REFERENCES

National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically—Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol, 20, No. 2, NCCLS, Wayne, PA, January 2000.

16 HOW SUPPLIED/STORAGE AND HANDLING

PRILOSEC Delayed-Release Capsules, 10 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 606 on cap and PRILOSEC 10 on the body. They are supplied as follows:

NDC 0186-0606-31 unit of use bottles of 30

PRILOSEC Delayed-Release Capsules, 20 mg, are opaque, hard gelatin, amethyst colored capsules, coded 742 on cap and PRILOSEC 20 on body. They are supplied as follows:

NDC 0186-0742-31 unit of use bottles of 30

NDC 0186-0742-82 bottles of 1000

PRILOSEC Delayed-Release Capsules, 40 mg, are opaque, hard gelatin, apricot and amethyst colored capsules, coded 743 on cap and PRILOSEC 40 on the body. They are supplied as follows:

NDC 0186-0743-31 unit of use bottles of 30

NDC 0186-0743-68 bottles of 100

PRILOSEC For Delayed-Release Oral Suspension, 2.5 mg or 10 mg, is supplied as a unit dose packet containing a fine yellow powder, consisting of white to brownish omeprazole granules and pale yellow inactive granules. PRILOSEC unit dose packets are supplied as follows:

NDC 0186-0625–01 unit dose packages of 30: 2.5 mg packets

NDC 0186-0610–01 unit dose packages of 30: 10 mg packets

Storage

Store PRILOSEC Delayed-Release Capsules in a tight container protected from light and moisture. Store between 15°C and 30°C (59°F and 86°F).

Store PRILOSEC For Delayed-Release Oral Suspension at 25°C (77°F); excursions permitted to 15 – 30°C (59 – 86°F). [See USP Controlled Room Temperature.]

17 PATIENT COUNSELING INFORMATION

“See FDA-Approved Medication Guide”

PRILOSEC should be taken before eating. Patients should be informed that the PRILOSEC Delayed-Release Capsule should be swallowed whole.

For patients who have difficulty swallowing capsules, the contents of a PRILOSEC Delayed-Release Capsule can be added to applesauce. One tablespoon of applesauce should be added to an empty bowl and the capsule should be opened. All of the pellets inside the capsule should be carefully emptied on the applesauce. The pellets should be mixed with the applesauce and then swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The pellets should not be chewed or crushed. The pellets/applesauce mixture should not be stored for future use.

PRILOSEC For Delayed-Release Oral Suspension should be administered as follows:

• •Empty the contents of a 2.5 mg packet into a container containing 5 mL of water.
• •Empty the contents of a 10 mg packet into a container containing 15 mL of water.
• •Stir
• •Leave 2 to 3 minutes to thicken.
• •Stir and drink within 30 minutes.
• •If any material remains after drinking, add more water, stir and drink immediately.

For patients with a nasogastric or gastric tube in place:

• •Add 5 mL of water to a catheter tipped syringe and then add the contents of a 2.5 mg packet (or 15 mL of water for the 10 mg packet). It is important to only use a catheter tipped syringe when administering PRILOSEC through a nasogastric tube or gastric tube.
• •Immediately shake the syringe and leave 2 to 3 minutes to thicken.
• •Shake the syringe and inject through the nasogastric or gastric tube, French size 6 or larger, into the stomach within 30 minutes.
• •Refill the syringe with an equal amount of water.
• •Shake and flush any remaining contents from the nasogastric or gastric tube into the stomach.

Advise patients to immediately report and seek care for diarrhea that does not improve. This may be a sign of Clostridium difficile associated diarrhea [see Warnings and Precautions (5.3) ].

Advise patients to immediately report and seek care for any cardiovascular or neurological symptoms including palpitations, dizziness, seizures, and tetany as these may be signs of hypomagnesemia [see Warnings and Precautions (5.6) ].

PRILOSEC is a trademark of the AstraZeneca group of companies.

Manufactured for: AstraZeneca LP, Wilmington, DE 19850

©AstraZeneca 2014

Rev. March 2014

MEDICATION GUIDE

PRILOSEC (pry-lo-sec)

(omeprazole)

delayed-release capsules

PRILOSEC (pry-lo-sec)

(omeprazole magnesium)

for delayed-release oral suspension

Read this Medication Guide before you start taking PRILOSEC and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about PRILOSEC?

PRILOSEC may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

PRILOSEC can cause serious side effects, including:

• • Diarrhea. PRILOSEC may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection (Clostridium difficile) in your intestines.
  Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.
• • Bone fractures. People who take multiple daily doses of proton pump inhibitor medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist, or spine. You should take PRILOSEC exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take PRILOSEC.

PRILOSEC can have other serious side effects. See “What are the possible side effects of PRILOSEC?”

What is PRILOSEC?

PRILOSEC is a prescription medicine called a proton pump inhibitor (PPI). PRILOSEC reduces the amount of acid in your stomach.

PRILOSEC is used in adults:

•  
  • •for up to 8 weeks for the healing of duodenal ulcers. The duodenal area is the area where food passes when it leaves the stomach.
  • •with certain antibiotics to treat an infection caused by bacteria called H. pylori. Sometimes H. pylori bacteria can cause duodenal ulcers. The infection needs to be treated to prevent the ulcers from coming back.
  • •for up to 8 weeks for healing stomach ulcers.
  • •for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD).
    GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour taste, or burping.
  • •for up to 8 weeks to heal acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). If needed, your doctor may decide to prescribe another 4 weeks of PRILOSEC.
  • •to maintain healing of the esophagus. It is not known if PRILOSEC is safe and effective when used for longer than 12 months (1 year) for this purpose.
  • •for the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome.

For children 1 to 16 years of age, PRILOSEC is used:

• •for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD).
• •for up to 8 weeks to heal acid-related damage to the lining of the esophagus (called erosive esophagitis or EE)
• •to maintain healing of the esophagus. It is not known if PRILOSEC is safe and effective when used longer than 12 months (1 year) for this purpose.

It is not known if PRILOSEC is safe and effective for the treatment of gastroesophageal reflux disease (GERD) in children under 1 year of age.

Who should not take PRILOSEC?

Do not take PRILOSEC if you:

• •are allergic to omeprazole or any of the ingredients in PRILOSEC. See the end of this Medication Guide for a complete list of ingredients in PRILOSEC.
• •are allergic to any other Proton Pump Inhibitor (PPI) medicine.

What should I tell my doctor before taking PRILOSEC?

Before you take PRILOSEC, tell your doctor if you:

• •have been told that you have low magnesium levels in your blood
• •have liver problems
• •have any other medical conditions
• •are pregnant or plan to become pregnant. It is not known if PRILOSEC will harm your unborn baby.
• •are breastfeeding or plan to breastfeed. PRILOSEC passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take PRILOSEC.

Tell your doctor about all of the medicines you take including prescription and non-prescription drugs, anti-cancer drugs, vitamins and herbal supplements. PRILOSEC may affect how other medicines work, and other medicines may affect how PRILOSEC works.

Especially tell your doctor if you take:

• •atazanavir (Reyataz)
• •nelfinavir (Viracept)
• •saquinavir (Fortovase)
• •cilostazol (Pletal)
• •ketoconazole (Nizoral)
• •voriconazole (Vfend)
• •an antibiotic that contains ampicillin, amoxicillin or clarithromycin
• •products that contain iron
• •warfarin (Coumadin, Jantoven)
• •digoxin (Lanoxin)
• •tacrolimus (Prograf)
• •diazepam (Valium)
• •phenytoin (Dilantin)
• •disulfiram (Antabuse)
• •clopidogrel (Plavix)
• •St. John’s Wort (Hypericum perforatum)
• •rifampin (Rimactane, Rifater, Rifamate),
• •erlotinib (Tarceva)
• •methotrexate

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take PRILOSEC?

• •Take PRILOSEC exactly as prescribed by your doctor.
• •Do not change your dose or stop PRILOSEC without talking to your doctor.
• •Take PRILOSEC at least 1 hour before a meal.
• •Swallow PRILOSEC capsules whole. Do not chew or crush PRILOSEC Capsules.
• •If you have trouble swallowing PRILOSEC Capsules, you may take as follows:
  • •Place 1 tablespoon of applesauce into a clean bowl.
  • •Carefully open the capsule and empty the contents (pellets) onto the applesauce. Mix the pellets with the applesauce.
  • •Swallow the applesauce and pellet mixture right away with a glass of cool water. Do not chew or crush the pellets. Do not store the applesauce and pellet mixture for later use.
• •If you forget to take a dose of PRILOSEC, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose on time. Do not take a double dose to make up for a missed dose.
• •If you take too much PRILOSEC, tell your doctor right away.
• •See the “Instructions for Use” at the end of this Medication Guide for instructions on how to take PRILOSEC For Delayed-Release Oral Suspension, and how to mix and give PRILOSEC For Delayed-Release Oral Suspension, through a nasogastric tube or gastric tube.

  What are the possible side effects of PRILOSEC?

  PRILOSEC can cause serious side effects, including:

The most common side effects with PRILOSEC in adults and children include:

• •headache
• •stomach pain
• •nausea
• •diarrhea
• •vomiting
• •gas

In addition to the side effects listed above, the most common side effects in children 1 to 16 years of age include:

• •respiratory system events
• •fever

Other side effects:

Serious allergic reactions. Tell your doctor if you get any of the following symptoms with PRILOSEC:

• •rash
• •face swelling
• •throat tightness
• •difficulty breathing

Your doctor may stop PRILOSEC if these symptoms happen.

Tell your doctor if you have any side effect that bothers you or that do not go away. These are not all the possible side effects with PRILOSEC.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store PRILOSEC?

• •Store PRILOSEC Delayed-Release Capsules at room temperature between 59°F to 86°F (15°C to 30°C).
• •Store PRILOSEC For Delayed-Release Oral Suspension at room temperature between 68°F to 77°F (20°C to 25°C).
• •Keep the container of PRILOSEC Delayed-Release Capsules closed tightly.
• •Keep the container of PRILOSEC Delayed-Release Capsules dry and away from light.

Keep PRILOSEC and all medicines out of the reach of children.

General information about PRILOSEC

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use PRILOSEC for a condition for which it was not prescribed. Do not give PRILOSEC to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about PRILOSEC. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals.

For more information, go to www.astrazeneca-us.com or call 1-800-236-9933.

Instructions for Use

For instructions on taking Delayed-Release Capsules, please see “How should I take PRILOSEC?”

Take PRILOSEC For Delayed-Release Oral Suspension as follows:

• •PRILOSEC For Delayed-Release Oral Suspension comes in packets containing 2.5 mg and 10 mg strengths.
• •You should use an oral syringe to measure the amount of water needed to mix your dose. Ask your pharmacist for an oral syringe.
• •If your prescribed dose is 2.5 mg, add 5 mL of water to a container, then add the contents of the packet containing your prescribed dose.
• •If your prescribed dose is 10 mg, add 15 mL of water to a container, then add the contents of the packet containing your prescribed dose.
• •If you or your child are instructed to use more than one packet for your prescribed dose, follow the mixing instructions provided by your pharmacist or doctor.
• •Stir.
• •Leave 2 to 3 minutes to thicken.
• •Stir and drink within 30 minutes. If not used within 30 minutes, throw away this dose and mix a new dose.
• •If any medicine remains after drinking, add more water, stir, and drink right away.

PRILOSEC For Delayed-Release Oral Suspension may be given through a nasogastric tube (NG tube) or gastric tube, as prescribed by your doctor. Follow the instructions below:

PRILOSEC For Delayed-Release Oral Suspension:

• •PRILOSEC For Delayed-Release Oral Suspension comes in packets containing 2.5 mg and 10 mg strengths.
• •Use only a catheter tipped syringe to give PRILOSEC through a NG tube or gastric tube (French size 6 or larger).
• •If your prescribed dose is 2.5 mg, add 5 mL of water to a catheter tipped syringe, then add the contents of the packet containing your prescribed dose.
• •If your prescribed dose is 10 mg, add 15 mL of water to a catheter tipped syringe, then add the contents of the packet containing your prescribed dose.
• •Shake the syringe right away and then leave it for 2 to 3 minutes to thicken.
• •Shake the syringe and give the medicine through the NG or gastric tube within 30 minutes.
• •Refill the syringe with the same amount of water (either 5 mL or 15 mL of water depending on your dose).
• •Shake the syringe and flush any remaining medicine from the NG tube or gastric tube into the stomach.

What are the ingredients in PRILOSEC?

Active ingredient in PRILOSEC Delayed-Release Capsules: omeprazole

Inactive ingredients in PRILOSEC Delayed-Release Capsules: cellulose, disodium hydrogen phosphate, hydroxypropyl cellulose, hypromellose, lactose, mannitol, sodium lauryl sulfate. Capsule shells: gelatin-NF, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, synthetic black iron oxide, isopropanol, butyl alcohol, FD&C Blue #2, D&C Red #7 Calcium Lake, and, in addition, the 10 mg and 40 mg capsule shells also contain D&C Yellow #10.

Active ingredient in PRILOSEC For Delayed-Release Oral Suspension: omeprazole magnesium

Inactive ingredients in PRILOSEC For Delayed-Release Oral Suspension: glyceryl monostearate, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer C, polysorbate, sugar spheres, talc, and triethyl citrate.

Inactive granules in PRILOSEC For Delayed-Release Oral Suspension: citric acid, crospovidone, dextrose, hydroxypropyl cellulose, iron oxide and xantham gum.

This Medication Guide and Instructions for Use has been approved by the U.S. Food and Drug Administration.

AstraZeneca Pharmaceuticals LP

Wilmington, DE 19850

Revised March 2014

PRILOSEC is a registered trademark of the AstraZeneca group of companies.

©2014 AstraZeneca Pharmaceuticals LP. All rights reserved.

Package/Label Display Panel – 10 mg Capsules

NDC 0186-0606-31

PRILOSEC^®

(omeprazole)

30 Delayed-Release Capsules

10 mg

Dispense the accompanying Medication Guide to each patient.

Rx only

AstraZeneca