The First and ONLY Immediate-Release Oral PPI
Clinical Summary of ZEGERID® (omeprazole/sodium bicarbonate)
What is ZEGERID® (omeprazole/sodium bicarbonate)?
ZEGERID (omeprazole/sodium bicarbonate) is a combination of omeprazole, a proton pump inhibitor (PPI), and sodium bicarbonate, an antacid, which raises intragastric pH and protects omeprazole from gastric acid degradation.1 ZEGERID is the first and only immediate–release oral PPI.2
What differentiates ZEGERID from other drugs in its class?
ZEGERID Capsules and Powder for Oral Suspension are unique among oral PPIs because they are immediate-release formulations, in contrast to all other oral PPIs, including capsules, disintegrating tablets, and suspensions, which are delayed-release, enteric-coated formulations.2 Unlike the enteric coatings used in other PPI formulations, the sodium bicarbonate in ZEGERID raises intragastric pH and protects omeprazole from degradation by gastric acid.1 The sodium bicarbonate in ZEGERID facilitates the rapid absorption of omeprazole, with peak plasma concentrations of omeprazole being reached approximately 30 minutes after each dose.1 Delayed–release omeprazole products or formulations — Prilosec®, Prilosec OTC®, and generic omeprazole — are not therapeutically equivalent to ZEGERID.3 There are no AB-rated generic equivalents to ZEGERID according to the FDA Orange Book.3
How effectively is acid controlled with bedtime administration of ZEGERID?
In reviewing the medical literature, many investigators recommend administering PPIs 15 to 30 minutes prior to meals to maximize acid suppression.4 Published data show that more than half (54%) of patients with poorly controlled gastroesophageal reflux disease (GERD) dose their PPIs suboptimally, and almost a third (28%) of patients who dose suboptimally take their PPIs at bedtime.4 A PPI that can be dosed at bedtime without regard to meals would benefit patients who require rapid and continued acid control throughout the night, as well as those who are noncompliant with premeal dosing.5
Two studies have been published in which ZEGERID Powder for Oral Suspension administered at bedtime, without a meal, controlled intragastric acidity throughout the night.* The more recent, published by Katz in 2007, was an open-label, randomized, crossover study of 49 patients with nocturnal symptoms of GERD comparing the effects of repeated bedtime administration of ZEGERID Powder for Oral Suspension 40 mg, lansoprazole 30 mg delayed-release capsules, and esomeprazole 40 mg delayed-release capsules on nocturnal gastric acidity.5 At steady state, a more rapid onset of control of nocturnal gastric acidity was observed with ZEGERID.5 After bedtime dosing at 10:00 PM, patients treated with ZEGERID first reached an intragastric pH > 4 at 10:15 PM, compared with 1:15 AM with esomeprazole and 3:15 AM with lansoprazole.5
Additionally, administration of ZEGERID at bedtime resulted in a substantial reduction in nocturnal acid breakthrough (NAB) compared with symmetric dosing of esomeprazole and lansoprazole.5 NAB was defined as gastric pH < 4 for more than 1 continuous hour from 10:00 PM to 6:00 AM.5 The percentage of patients who experienced NAB was significantly lower following treatment with ZEGERID compared with esomeprazole or lansoprazole (61.2% vs 91.8% and 91.8%, respectively; P < 0.001, both comparisons).5
Control of intragastric pH in the early part of the sleeping period may be important when managing patients who require control of nocturnal gastric acidity.6 Recent findings published by Hila and Castell suggest that episodes of abnormal nocturnal acid reflux are significantly more frequent during the first half of the night than during the second half.6 During the first half of the night (10:00 PM to 2:00 AM), the percentage of time gastric pH > 4 was significantly greater with ZEGERID than with esomeprazole or lansoprazole (51.9% vs 30.1% and 12.0%, respectively; P < 0.001, both comparisons).5 Median gastric pH was also significantly higher during the first half of the night with bedtime administration of ZEGERID compared with bedtime administration of esomeprazole or lansoprazole (4.34 vs 2.37 and 1.51, respectively; P < 0.001, both comparisons).5
Control of nocturnal gastric acidity during the 8-hour nighttime period (10:00 PM to 6:00 AM) was significantly better with ZEGERID than with lansoprazole.5 The percentage of time gastric pH > 4 for the 8-hour nighttime period was significantly greater with ZEGERID than with lansoprazole (53.4% vs 34.2%; P < 0.001).5 Median gastric pH for the same time interval was 4.04 with ZEGERID compared with 2.09 with lansoprazole (P < 0.001).5 Following bedtime administration of esomeprazole, the percentage of time gastric pH > 4 was 54.9%, and median gastric pH was 4.85.5 Although overall nighttime acid control achieved with bedtime administration of esomeprazole was comparable to that observed with ZEGERID, control of early nighttime gastric acidity, from 10:00 PM to 2:00 AM, was significantly better with ZEGERID than with esomeprazole (median gastric pH: 4.34 vs 2.37, respectively; P < 0.001; percentage of time gastric pH > 4: 51.9% vs 30.1%, respectively; P < 0.001).5 No serious safety issues were associated with any of the drugs in this trial.5
Another study of bedtime administration of ZEGERID, published in 2005, was a randomized, open–label, 2–period crossover trial of 32 patients with nocturnal symptoms of GERD comparing the effects of ZEGERID Powder for Oral Suspension 40 mg and pantoprazole 40 mg delayed–release tablets on nocturnal gastric acidity.7 Repeated once–daily dosing of ZEGERID at bedtime produced significantly better nocturnal gastric acid control than repeated once–daily (predinner) or twice–daily (prebreakfast and bedtime) dosing with pantoprazole (median gastric pH: 4.7 vs 2.0 and 1.7, respectively; P < 0.001, both comparisons; percentage of time gastric pH > 4: 55% vs 27% and 34%, respectively; P < 0.001, both comparisons).7 Repeated once–daily bedtime dosing with ZEGERID 40 mg and twice–daily dosing with pantoprazole 40 mg resulted in similar 24–hour gastric pH control. No serious safety issues were associated with either drug in this trial.7 The investigators concluded that ZEGERID 40 mg dosed once daily at bedtime reduced nocturnal gastric acidity to a degree not observed with either once–daily or twice–daily dosing of delayed–release pantoprazole 40 mg.7
How effectively is acid controlled with daytime administration of ZEGERID?
Separate pharmacokinetic and pharmacodynamic studies of the antisecretory effects of repeated once–daily, prebreakfast dosing of ZEGERID Capsules and Powder for Oral Suspension have been conducted. Median values for the time gastric pH > 4 for patients taking ZEGERID Powder for Oral Suspension and ZEGERID Capsules, 20 mg and 40 mg doses, ranged from 12.2 to 18.6 hours on Day 7 (steady state).1 ZEGERID has a distinct pharmacokinetic profile, provides acid control for up to 24 hours, offers once–a–day bedtime or daytime dosing, and can be administered on an empty stomach at least 1 hour before a meal.1,5,8
For what indications is ZEGERID approved?1
ZEGERID is indicated for heartburn and other symptoms associated with gastroesophageal reflux disease (GERD) (20 mg); for the short-term treatment (4–8 weeks) of erosive esophagitis diagnosed by endoscopy (20 mg); for maintenance of healing of erosive esophagitis (20 mg) (controlled studies do not extend beyond 12 months); for short-term treatment (4–8 weeks) of active duodenal ulcer (20 mg); for short-term treatment (4–8 weeks) of active benign gastric ulcer (40 mg); and for reduction of risk of upper gastrointestinal bleeding in critically ill patients (only powder for oral suspension 40 mg; use beyond 14 days has not been evaluated).
What important safety information do healthcare professionals need to know?1
The most frequently reported adverse events with ZEGERID are headache, diarrhea, and abdominal pain. In 178 critically ill patients treated with ZEGERID Powder for Oral Suspension, adverse events generally reflected the serious, underlying medical condition of the patients, but some adverse events occurred with more frequency in patients treated with ZEGERID Powder for Oral Suspension than in those treated with the comparator (acid-controlling) drug. For more information about these and other events, please see Table 13 of the full Prescribing Information. Symptomatic response to therapy does not preclude the presence of gastric malignancy. Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long term with omeprazole.
ZEGERID Capsules contain 304 mg of sodium per dose. ZEGERID Powder for Oral Suspension contains 460 mg of sodium per dose. This should be taken into consideration for patients on a sodium-restricted diet.
Sodium bicarbonate is contraindicated in patients with metabolic alkalosis and hypocalcemia. ZEGERID is contraindicated in patients with known hypersensitivity to any component of the formulation.
Since both 20 mg and 40 mg ZEGERID contain the same amount of sodium bicarbonate (1100 mg in capsules, 1680 mg in packets of powder for oral suspension), two 20 mg capsules are not equivalent to, and should not be substituted for, one 40 mg capsule, and two 20 mg packets are not equivalent to, and should not be substituted for, one 40 mg packet.
Please see accompanying full Prescribing Information for additional information.
*The correlation of pharmacodynamic data to clinical effect has not been established.
Next: There is No Substitute for ZEGERID
Prilosec and Prilosec OTC are registered trademarks of the AstraZeneca group of companies.
References
- ZEGERID Prescribing Information. Santarus, Inc. January 2008
- Castell D. Review of immediate-release omeprazole for the treatment of gastric acid-related disorders. Expert Opin Pharmacother. 2005;6:2501-2510.
- FDA Web site. Electronic Orange Book. http://www.fda.gov/cder/ob/default.htm. Accessed June 13, 2008.
- Gunaratnam NT, Jessup TP, Inadomi J, Lascewski DP. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006;23:1473-1477
- Katz PO, Koch FK, Ballard ED, et al. Comparison of the effects of immediate-release omeprazole oral suspension, delayed-release lansoprazole capsules and delayed-release esomeprazole capsules on nocturnal gastric acidity after bedtime dosing in patients with night-time GERD symptoms. Aliment Pharmacol Ther. 2007;25:197-205.
- Hila A, Castell DO. Nighttime reflux is primarily an early event. J Clin Gastroenterol. 2005;39:579-583
- Castell D, Bagin R, Goldlust B, Major J, Hepburn B. Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2005;21:1467-1474.
- Howden CW, Ballard ED, Koch FK, et al. Control of 24–hour intragastric acidity with morning dosing of immediate-release and delayed-release proton pump inhibitors in patients with GERD. Poster presented at: Digestive Disease Week; May 17–22, 2008; San Diego, CA.
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