Omeprazole/Bicarbonate (Page 8 of 10)

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 in Table 11.

Table 11: % Successful Symptomatic Outcome *

	Omeprazole 20 mg a.m.	Omeprazole 10 mg a.m.	Placebo a.m.
* Defined as complete resolution of heartburn † (p < 0.005) versus 10 mg ‡ (p < 0.005) versus placebo
All patients	46†, ‡(n=205)	31‡(n=199)	13(n=105)
Patients with confirmed GERD	56†, ‡(n=115)	36‡(n=109)	14(n=59)

Erosive Esophagitis — In a U.S. multicenter, double-blind, placebo controlled study of 40 mg or 20 mg of omeprazole 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 shown in Table 12.

Table 12: % Patients Healed

	Omeprazole 40 mg (n=87)	Omeprazole 20 mg (n=83)	Placebo (n=43)
* (p < 0.01) Omeprazole versus placebo.
Week 4	45*	39*	7
Week 8	75*	74*	14

In this study, the 40 mg dose was not superior to the 20 mg dose of omeprazole in the percentage healing rate. Other controlled clinical trials have also shown that omeprazole is effective in severe GERD. In comparisons with histamine H₂ -receptor antagonists in patients with erosive esophagitis, grade 2 or above, omeprazole 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 omeprazole 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%).

14.4 Long-Term Maintenance Treatment of Erosive Esophagitis

In a U.S. double-blind, randomized, multicenter, placebo-controlled study; two dose regimens of omeprazole were studied in patients with endoscopically confirmed healed esophagitis. Results to determine maintenance of healing of erosive esophagitis are shown in Table 13.

Table 13: Life Table Analysis

	Omeprazole 20 mg once daily (n=138)	Omeprazole 20 mg 3 days per week (n=137)	Placebo (n=131)
* (p < 0.01) omeprazole 20 mg once daily versus omeprazole 20 mg 3 consecutive days per week or placebo.
Percent in endoscopic remission at 6 months	70*	34	11

In an international, multicenter, double-blind study, omeprazole 20 mg daily and 10 mg daily were compared to ranitidine 150 mg twice daily in patients with endoscopically confirmed healed esophagitis. Table 14 provides the results of this study for maintenance of healing of erosive esophagitis.

Table 14: Life Table Analysis

	Omeprazole 20 mg once daily (n=131)	Omeprazole 10 mg once daily (n=133)	Ranitidine 150 mg twice daily (n=128)
* (p = 0.01) omeprazole 20 mg once daily versus omeprazole 10 mg once daily or Ranitidine. † (p = 0.03) omeprazole 10 mg once daily versus Ranitidine.
Percent in Endoscopic Remission at 12 Months	77*	58†	46

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

15 REFERENCES

1.

Friedman JM and Polifka JE. Omeprazole. In: Teratogenic Effects of Drugs: A Resource for Clinicians (TERIS). 2^nd ed. Baltimore, MD: The Johns Hopkins University Press 2000; p. 516.

2.

Källén BA. Use of omeprazole during pregnancy – no hazard demonstrated in 955 infants exposed during pregnancy. Eur J Obstet Gynecol Reprod Biol 2001 May;96(1):63-8.

3.

Ruigómez A, García Rodríquez LA, Cattaruzzi C, et al. Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol. 1999 Sep 1;150:476-81.

4.

Lalkin A, Loebstein R, Addis A, et al. The safety of omeprazole during pregnancy: a multicenter prospective controlled study. Am J Obstet Gynecol. 1998 Sep 1:179 (3 Pt 1):727-30.