Prilosec (omeprazole magnesium)  - 6 indications

• eradication of Helicobacter pylori; approved March 2008
• the treatment of gastric ulcers; approved March 2008
• the treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 1 year of age and older; approved March 2008
• erosive esophagitis (EE) due to acid-mediated GERD in patients 1 year of age and older; approved March 2008
• maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older; approved March 2008
• pathologic hypersecretory conditions in adults; approved March 2008

General Information

Prilosec (omeprazole magnesium) is a proton pump inhibitor.

Prilosec was originally approved 1989 as delayed-release pellet capsules. This formulation was subsequently discontinued.

Prilosec was subsequently approved in March of 2008 as a delayed-release oral suspension for the following indications:

• for short-term treatment of active duodenal ulcer in adults
• for the eradication of H. pylori to reduce the risk of duodenal ulcer recurrence: 
  • in combination with clarithromycin and amoxicillin for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults
  • in combination with clarithromycin for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H. pylori in adults
• for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults
• for the treatment of heartburn and other symptoms associated with GERD for up to 4 weeks in patients 1 year of age and older
• for the short-term treatment (4 to 8 weeks) of EE due to acid-mediated GERD that has been diagnosed by endoscopy in patients 1 year of age and older
• for the maintenance healing of EE due to acid-mediated GERD in patients 1 year of age and older
• for pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults

Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Prilosec (omeprazole) belongs to a class of anti-secretory 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.

Side Effects

Adverse effects associated with the use of Prilosec in adults may include, but are not limited to, the following:

• headache
• abdominal pain
• nausea
• diarrhea
• vomiting
• flatulence

Adverse effects associated with the use of Prilosec in pediatric patients (1 to 16 years of age) is similar to those reported in adults, with the exception of respiratory system events and fever, which were frequently reported in pediatric studies.

Indication 1 - eradication of Helicobacter pylori

approved March 2008

Dosing/Administration

Triple Therapy:

• Prilosec 20 mg Amoxicillin 1000 mg Clarithromycin 500 mg
• Take all three drugs twice daily for 10 days
• In patients with an ulcer present at the time of initiation of therapy, continue Prilosec 20 mg once daily for an additional 18 days for ulcer healing and symptom relief

Dual Therapy:

• Prilosec 40 mg once daily Clarithromycin 500 mg
• Take both drugs three times daily for 14 days
• In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of Prilosec 20 mg once daily is recommended for ulcer healing and symptom relief

Clinical Trial Results

Triple Therapy (omeprazole magnesium delayed-release capsules/clarithromycin/amoxicillin)

Three US, randomized, double-blind clinical studies in patients with H. pylori infection and duodenal ulcer disease (n = 558) compared omeprazole magnesium delayed-release capsules 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 omeprazole magnesium delayed-release capsules 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 omeprazole magnesium delayed-release capsules 20 mg once daily. Endpoints studied were the percentage of patients (per protocol) with eradication of H. pylori. Results are as follows: 

• Study 1: 77% with triple therapy versus 43% with clarithromycin plus amoxicillin alone
• Study 2: 78% with triple therapy versus 41% with clarithromycin plus amoxicillin alone
• Study 3: 90% with triple therapy versus 33% with clarithromycin plus amoxicillin alone

Dual Therapy (omeprazole magnesium delayed-release capsules/clarithromycin)

Four randomized, double-blind, multi-center studies (4, 5, 6, and 7) evaluated omeprazole magnesium delayed-release capsules 40 mg once daily plus clarithromycin 500 mg three times daily for 14 days, followed by omeprazole magnesium delayed-release capsules 20 mg once daily, (Studies 4, 5, and 7) or by omeprazole magnesium delayed-release capsules 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 omeprazole magnesium delayed-release capsules 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. Results are as follows (percentage of patients with H. pylori eradication):

U.S. Studies

• Study 4: 74% vs. 0% vs. 31%
• Study 5: 64% vs. 0% vs. 39%

Non - U.S. Studies

• Study 6: 83% vs. 1%
• Study 7: 74% vs. 1%

Indication 2 - the treatment of active duodenal ulcers and active benign gastric ulcers 

approved March 2008

Dosing/Administration

active duodenal ulcers

• 20 mg once daily for four weeks

active benign gastric ulcers

• 40 mg once daily for 4 to 8 weeks

Clinical Trial Results

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 omeprazole magnesium delayed-release capsules 20 mg once daily than with placebo.

• Week 2: 41% versus 13%
• Week 4: 75% versus 27%

Complete daytime and nighttime pain relief occurred significantly faster in patients treated with omeprazole magnesium delayed-release capsules 20 mg than in patients treated with placebo. At the end of the study, significantly more patients who had received omeprazole magnesium delayed-release capsules had complete relief of daytime pain and nighttime pain.

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 omeprazole magnesium delayed-release capsules 20 mg once daily than with ranitidine 150 mg b.i.d. Healing occurred significantly faster in patients treated with omeprazole magnesium delayed-release capsules than in those treated with ranitidine 150 mg b.i.d.

In a foreign multinational randomized, double-blind study of 105 patients with endoscopically documented duodenal ulcer, 20 mg and 40 mg of omeprazole magnesium delayed-release capsules 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 omeprazole magnesium delayed-release capsules, and at 8 weeks there was no significant difference between any of the active drugs.

Active Benign Gastric Ulcer

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

Week 4: 47.5% vs. 55.6% vs. 30.8%

Week 8: 74.8% vs. 82.7% vs. 2 48%

Indication 3 - the treatment of symptomatic GERD in patients 1 year of age and older

approved March 2008

Dosing/Administration

Adults: 20 mg once daily for up to 4 weeks

Pediatrics 1 to 16 years of age:

• weight-based dose, once daily for up to 4 weeks:
  • 5 to less than 10 kg: 5 mg
  • 10 to less than 20 kg: 10 mg
  • 20 kg and greater: 20 mg

Clinical Trial Results

Adults: 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 EE. The percentage of patients with symptomatic improvement per treatment arm, respectively, were: 56% vs. 36% vs. 14%.

Pediatrics: The effectiveness of omeprazole magnesium delayed-release capsules for the treatment of symptomatic GERD in pediatric patients 1 to 16 years of age is based in part on data obtained from 125 pediatric patients in two uncontrolled clinical studies. 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 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 symptomatic 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.

Indication 4 - treatment of EE due to acid-mediated GERD in patients 1 year of age and older

approved March 2008

Dosing/Administration

Adults: 20 mg once daily for 4 to 8 weeks

Pediatrics (1 to 16 years of age):

• weight-based dose, once daily for up to 4 weeks:
  • 5 to less than 10 kg: 5 mg
  • 10 to less than 20 kg: 10 mg
  • 20 kg and greater: 20 mg

Pediatrics (1 month to less than 1 year)

• weight-based dose, once daily for up to 6 weeks
  • 3 to less than 5 kg: 2.5 mg
  •  5 to less than 10 kg: 5 mg
  • 10 kg and greater: 10 mg

Clinical Trial Results

Adults: In a US multicenter double-blind placebo controlled study of 20 mg or 40 mg of omeprazole magnesium delayed-release capsules in patients with symptoms of GERD and endoscopically diagnosed EE of grade 2 or above, the percentage healing rates (per protocol) were as follows:

• Week 4: 39% vs. 45% vs. 7%
• Week 8: 74% vs. 75% vs. 14%

Pediatrics: In an uncontrolled, open-label dose-titration study, for the treatment of EE 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. EE 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.

Indication 5 - maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older

approved March 2008

Dosing/Administration

Adults: 20 mg once daily. Controlled studies do not extend beyond 12 months of treatment.

Pediatrics (1 to 16 years of age):

• weight-based dose, once daily. Controlled studies do not extend beyond 12 months.
  • 5 to less than 10 kg: 5 mg
  • 10 to less than 20 kg: 10 mg
  • 20 kg and greater: 20 mg

Clinical Trial Results

Adults: In a U.S. double-blind, randomized, multicenter, placebo controlled study, two dose regimens of omeprazole magnesium delayed-release capsules were studied in patients with endoscopically confirmed healed esophagitis. Results to determine maintenance of healing of EE are shown below.

Percent patients in endoscopic remission at 6 months:

• omeprazole magnesium delayed-release capsules 20 mg once daily (n = 138): 70%
• omeprazole magnesium delayed-release capsules 20 mg 3 days per week (n = 137): 34%
• Placebo (n = 131): 11%

Pediatrics: In an uncontrolled, open-label study of maintenance of healing of EE in 46 pediatric patients 1 to 16 years of age, 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 during follow-up (range 4 to 25 months). In addition, maintenance therapy in EE patients resulted in 63% of patients having no overall symptoms.

Indication 6 - pathologic hypersecretory conditions in adults

approved March 2008

Dosing/Administration

The recommended starting dose is 60 mg once daily; adjust to patient needs. Daily dosages of greater than 80 mg should be administered in divided doses. Dosages up to 120 mg three times daily have been administered. Continue to treat as long as clinically indicated. Some patients with Zollinger Ellison syndrome have been treated continuously for more than 5 years.

Clinical Trial Results

In open studies of 136 patients with pathological hypersecretory conditions, such as Zollinger-Ellison (ZE) syndrome with or without multiple endocrine adenomas, omeprazole magnesium 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.