Lansoprazole (lansoprazole 15 mg) Dailymed

14.1 Duodenal Ulcer

In a U.S. multicenter, double-blind, placebo-controlled, dose-response (15, 30, and 60 mg of lansoprazole once daily) study of 284 patients with endoscopically documented duodenal ulcer, the percentage of patients healed after two and four weeks was significantly higher with all doses of lansoprazole than with placebo. There was no evidence of a greater or earlier response with the two higher doses compared with lansoprazole 15 mg. Based on this study and the second study described below, the recommended dose of lansoprazole in duodenal ulcer is 15 mg per day (Table 9).

Table 9. Duodenal Ulcer Healing Rates
Week	Lansoprazole			Placebo (N=72)
	15 mg daily (N=68)	30 mg daily (N=74)	60 mg daily (N=70)
2	42.4%*	35.6%*	39.1%*	11.3%
4	89.4%*	91.7%*	89.9%*	46.1%

* (p≤0.001) versus placebo.

Lansoprazole 15 mg was significantly more effective than placebo in relieving day and nighttime abdominal pain and in decreasing the amount of antacid taken per day.

In a second U.S. multicenter study, also double-blind, placebo-controlled, dose-comparison (15 and 30 mg of lansoprazole once daily), and including a comparison with ranitidine, in 280 patients with endoscopically documented duodenal ulcer, the percentage of patients healed after four weeks was significantly higher with both doses of lansoprazole than with placebo. There was no evidence of a greater or earlier response with the higher dose of lansoprazole. Although the 15 mg dose of lansoprazole was superior to ranitidine at four weeks, the lack of significant difference at two weeks and the absence of a difference between 30 mg of lansoprazole and ranitidine leaves the comparative effectiveness of the two agents undetermined (Table 10) [see Indications and Usage ( 1.1 )]

Table 10. Duodenal Ulcer Healing Rates
Week	Lansoprazole		Ranitidine	Placebo (N=41)
	15 mg daily (N=80)	30 mg daily (N=77)	300 mg h.s. (N=82)
2	35.0%	44.2%	30.5%	34.2%
4	92.3%*	80.3%†	70.5%†	47.5%

* (p≤0.05) versus placebo and ranitidine. ^† (p≤0.05) versus placebo.

14.2 Eradication of

Randomized, double-blind clinical studies performed in the U.S. in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) evaluated the efficacy of lansoprazole in combination with amoxicillin and clarithromycin as triple 14 day therapy or in combination with amoxicillin as dual 14 day therapy for the eradication of H. pylori. Based on the results of these studies, the safety and efficacy of two different eradication regimens were established:

Triple therapy: Lansoprazole 30 mg twice daily/amoxicillin 1 g twice daily/clarithromycin 500 mg twice daily

Dual therapy: Lansoprazole 30 mg three times daily/amoxicillin 1 g three times daily

All treatments were for 14 days. H. pylori eradication was defined as two negative tests (culture and histology) at four to six weeks following the end of treatment.

Triple therapy was shown to be more effective than all possible dual therapy combinations. Dual therapy was shown to be more effective than both monotherapies. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

A randomized, double-blind clinical study performed in the U.S. in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) compared the efficacy of lansoprazole triple therapy for 10 and 14 days. This study established that the 10 day triple therapy was equivalent to the 14 day triple therapy in eradicating H. pylori (Tables 11 and 12) [see Indications and Usage (1.2)]

Table 11. H. pylori Eradication Rates – Triple Therapy (lansoprazole/amoxicillin/clarithromycin) Percent of Patients Cured [95% Confidence Interval] (Number of patients)
Study	Duration	Triple Therapy Evaluable Analysis*	Triple Therapy Intent-to-Treat Analysis†
M93-131	14 days	92‡	86‡
		[80.0–97.7]	[73.3–93.5]
		(N=48)	(N=55)
M95-392	14 days	86§	83§
		[75.7–93.6]	[72.0–90.8]
		(N=66)	(N=70)
M95-399¶	14 days	85	82
		[77.0–91.0]	[73.9–88.1]
		(N=113)	(N=126)
	10 days	84	81
		[76.0–89.8]	[73.9–87.6]
		(N=123)	(N=135)

* Based on evaluable patients with confirmed duodenal ulcer (active or within one year) 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 evaluable analysis as failures of therapy. ^† Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within one year). All dropouts were  included as failures of therapy. ^‡ (p<0.05) versus lansoprazole/amoxicillin and lansoprazole/clarithromycin dual therapy ^§ (p<0.05) versus clarithromycin/amoxicillin dual therapy. ^¶ The 95% confidence interval for the difference in eradication rates, 10-day minus 14-day  is (-10.5, 8.1) in the evaluable analysis and (-9.7, 9.1) in the intent-to-treat analysis.

Table 12 H. pylori Eradication Rates – 14 Day Dual Therapy (lansoprazole/amoxicillin) Percent of Patients Cured [95% Confidence Interval] (Number of patients)
Study	Dual Therapy Evaluable Analysis*	Dual Therapy Intent-to-Treat Analysis†
M93-131	77‡	70‡
	[62.5–87.2]	[56.8–81.2]
	(N=51)	(N=60)
M93-125	66§	61§
	[51.9–77.5]	[48.5–72.9]
	(N=58)	(N=67)

* Based on evaluable patients with confirmed duodenal ulcer (active or within one year) 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. ^{† Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within one year). All dropouts were included as failures of therapy. ‡ (p<0.05) versus lansoprazole alone. § (p<0.05) versus lansoprazole alone or amoxicillin alone.}

14.3 Maintenance of Healed Duodenal Ulcers

Lansoprazole has been shown to prevent the recurrence of duodenal ulcers. Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed duodenal ulcers. Patients remained healed significantly longer and the number of recurrences of duodenal ulcers was significantly less in patients treated with lansoprazole than in patients treated with placebo over a 12-month period (Table 13) [see Indications and Usage ( 1.4)]

Table 13 Endoscopic Remission Rates
Trial	Drug	No. of Pts.	Percent in Endoscopic Remission
			0–3 mo.	0–6 mo.	0–12 mo.
#1	Lansoprazole 15 mg daily	86	90%*	87%*	84%*
	Placebo	83	49%	41%	39%
#2	Lansoprazole 30 mg daily	18	94%*	94%*	85%*
	Lansoprazole 15 mg daily	15	87%*	79%*	70%*
	Placebo	15	33%	0%	0%

%=Life Table Estimate *(p≤0.001) versus placebo.  

In trial #2, no significant difference was noted between lansoprazole 15 mg and 30 mg in maintaining remission.

14.4 Gastric Ulcer

In a U.S. multicenter, double-blind, placebo-controlled study of 253 patients with endoscopically documented gastric ulcer, the percentage of patients healed at four and eight weeks was significantly higher with lansoprazole 15 mg and 30 mg once a day than with placebo (Table 14) [see Indications and Usage ( 1.4)]

Table 14. Gastric Ulcer Healing Rates
	Lansoprazole			Placebo (N=64)
Week	15 mg daily (N=65)	30 mg daily (N=63)	60 mg daily (N=61)
4	64.6%*	58.1%*	53.3%*	37.5%
8	92.2%*	96.8%*	93.2%*	76.7%

* (p≤0.05) versus placebo.

Patients treated with any lansoprazole dose reported significantly less day and night abdominal pain along with fewer days of antacid use and fewer antacid tablets used per day than the placebo group.

Independent substantiation of the effectiveness of lansoprazole 30 mg was provided by a meta-analysis of published and unpublished data.

14.5 Healing of NSAID-Associated Gastric Ulcer

In two U.S. and Canadian multicenter, double-blind, active-controlled studies in patients with endoscopically confirmed NSAID-associated gastric ulcer who continued their NSAID use, the percentage of patients healed after eight weeks was statistically significantly higher with 30 mg of lansoprazole than with the active control. A total of 711 patients were enrolled in the study, and 701 patients were treated. Patients ranged in age from 18 to 88 years (median age 59 years), with 67% female patients and 33% male patients. Race was distributed as follows: 87% Caucasian, 8% Black, 5% Other. There was no statistically significant difference between lansoprazole 30 mg daily and the active control on symptom relief (i.e., abdominal pain) (Table 15) [see Indications and Usage ( 1.5)].

Table 15. NSAID-Associated Gastric Ulcer Healing Rates*
Study #1
	Lansoprazole 30 mg daily	Active Control†
Week 4	60% (53/88) ‡	28% (23/83)
Week 8	79% (62/79) ‡	55% (41/74)
Study #2
	Lansoprazole 30 mg daily	Active Control†
Week 4	53% (40/75)	38% (31/82)
Week 8	77% (47/61) ‡	50% (33/66)

* Actual observed ulcer(s) healed at time points ± 2 days ^† Dose for healing of gastric ulcer ^‡ (p≤0.05) versus the active control

14.6 Risk Reduction of NSAID-Associated Gastric Ulcer

In one large U.S., multicenter, double-blind, placebo- and misoprostol-controlled (misoprostol blinded only to the endoscopist) study in patients who required chronic use of an NSAID and who had a history of an endoscopically documented gastric ulcer, the proportion of patients remaining free from gastric ulcer at four, eight, and 12 weeks was significantly higher with 15 or 30 mg of lansoprazole than placebo. A total of 537 patients were enrolled in the study, and 535 patients were treated. Patients ranged in age from 23 to 89 years (median age 60 years), with 65% female patients and 35% male patients. Race was distributed as follows: 90% Caucasian, 6% Black, 4% other. The 30 mg dose of lansoprazole demonstrated no additional benefit in risk reduction of the NSAID-associated gastric ulcer than the 15 mg dose (Table 16) [see Indications and Usage ( 1.6)].

Table 16. Proportion of Patients Remaining Free of Gastric Ulcers*
Week	Lansoprazole 15 mg daily	Lansoprazole 30 mg daily	Misoprostol 200 mcg four times daily	Placebo
	(N=121)	(N=116)	(N=106)	(N=112)
4	90%	92%	96%	66%
8	86%	88%	95%	60%
12	80%	82%	93%	51%

* % = Life Table Estimate (p<0.001) lansoprazole 15 mg daily versus placebo; lansoprazole 30 mg daily versus placebo; and misoprostol 200 mcg four times daily versus placebo. (p<0.05) Misoprostol 200 mcg four times daily versus lansoprazole 15 mg daily; and misoprostol 200 mcg four times daily versus lansoprazole 30 mg daily.

14.7 Symptomatic Gastroesophageal Reflux Disease (GERD)

Symptomatic GERD: In a U.S. multicenter, double-blind, placebo-controlled study of 214 patients with frequent GERD symptoms, but no esophageal erosions by endoscopy, significantly greater relief of heartburn associated with GERD was observed with the administration of lansoprazole 15 mg once daily up to eight weeks than with placebo. No significant additional benefit from lansoprazole 30 mg once daily was observed.

The intent-to-treat analyses demonstrated significant reduction in frequency and severity of day and night heartburn. Data for frequency and severity for the eight week treatment period are presented in Table 17 and in Figures 1 and 2:

Table 17. Frequency of Heartburn
	Placebo	Lansoprazole 15 mg	Lansoprazole 30 mg
Variable	(n=43)	(n=80)	(n=86)
	Median
% of Days without Heartburn
Week 1	0%	71%*	46%*
Week 4	11%	81%*	76%*
Week 8	13%	84%*	82%*
% of Nights without Heartburn
Week 1	17%	86%*	57%*
Week 4	25%	89%*	73%*
Week 8	36%	92%*	80%*

*(p<0.01) versus placebo.

Figure 1



Figure 2



In two U.S., multicenter double-blind, ranitidine-controlled studies of 925 total patients with frequent GERD symptoms, but no esophageal erosions by endoscopy, lansoprazole 15 mg was superior to ranitidine 150 mg (twice daily) in decreasing the frequency and severity of day and night heartburn associated with GERD for the eight week treatment period. No significant additional benefit from lansoprazole 30 mg once daily was observed [see Indications and Usage (1.7)]

14.8 Erosive Esophagitis

In a U.S. multicenter, double-blind, placebo-controlled study of 269 patients entering with an endoscopic diagnosis of esophagitis with mucosal grading of two or more and grades three and four signifying erosive disease, the percentages of patients with healing are presented in Table 18:

Table 18. Erosive Esophagitis Healing Rates
Week	Lansoprazole			Placebo
	15 mg daily	30 mg daily	60 mg daily
	(N=69)	(N=65)	(N=72)	(N=63)
4	67.6%*	81.3%*†	80.6%*†	32.8%
6	87.7%*	95.4%*	94.3%*	52.5%
8	90.9%*	95.4%*	94.4%*	52.5%

*(p≤0.001) versus placebo. ^†(p≤0.05) versus lansoprazole 15 mg.

In this study, all lansoprazole groups reported significantly greater relief of heartburn and less day and night abdominal pain along with fewer days of antacid use and fewer antacid tablets taken per day than the placebo group. Although all doses were effective, the earlier healing in the higher two doses suggests 30 mg daily as the recommended dose.

Lansoprazole was also compared in a U.S. multicenter, double-blind study to a low dose of ranitidine in 242 patients with erosive reflux esophagitis. Lansoprazole at a dose of 30 mg was significantly more effective than ranitidine 150 mg twice daily as shown below (Table 19).

Table 19. Erosive Esophagitis Healing Rates
Week	Lansoprazole 30 mg daily (N=115)	Ranitidine 150 mg twice daily (N=127)
2	66.7%*	38.7%
4	82.5%*	52.0%
6	93.0%*	67.8%
8	92.1%*	69.9%

*(p≤0.001) versus ranitidine.

In addition, patients treated with lansoprazole reported less day and nighttime heartburn and took less antacid tablets for fewer days than patients taking ranitidine 150 mg twice daily.

Although this study demonstrates effectiveness of lansoprazole in healing erosive esophagitis, it does not represent an adequate comparison with ranitidine because the recommended ranitidine dose for esophagitis is 150 mg four times daily, twice the dose used in this study.

In the two trials described and in several smaller studies involving patients with moderate to severe erosive esophagitis, lansoprazole produced healing rates similar to those shown above. In a U.S. multicenter, double-blind, active-controlled study, 30 mg of lansoprazole was compared with ranitidine 150 mg twice daily in 151 patients with erosive reflux esophagitis that was poorly responsive to a minimum of 12 weeks of treatment with at least one H₂-receptor antagonist given at the dose indicated for symptom relief or greater, namely, cimetidine 800 mg/day, ranitidine 300 mg/day, famotidine 40 mg/day or nizatidine 300 mg/day. Lansoprazole 30 mg was more effective than ranitidine 150 mg twice daily in healing reflux esophagitis, and the percentage of patients with healing were as follows. This study does not constitute a comparison of the effectiveness of histamine H₂-receptor antagonists with lansoprazole, as all patients had demonstrated unresponsiveness to the histamine H₂-receptor antagonist mode of treatment. It does indicate, however, that lansoprazole may be useful in patients failing on a histamine H₂-receptor antagonist (Table 20) [see Indications and Usage ( 1.7)]

Table 20. Reflux Esophagitis Healing Rates in Patients Poorly Responsive to Histamine H2-Receptor Antagonist Therapy
Week	Lansoprazole 30 mg daily (N=100)	Ranitidine 150 mg twice daily (N=51)
4	74.7%*	42.6%
8	83.7%*	32.0%

*(p≤0.001) versus ranitidine.

14.9 Maintenance of Healing of Erosive Esophagitis

Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed esophagitis. Patients remained in remission significantly longer and the number of recurrences of erosive esophagitis was significantly less in patients treated with lansoprazole than in patients treated with placebo over a 12-month period (Table 21).

Table 21. Endoscopic Remission Rates
			Percent in Endoscopic Remission
Trial	Drug	No. of Pts.	0–3 mo.	0–6 mo.	0–12 mo.
#1	Lansoprazole 15 mg daily	59	83%*	81%*	79%*
	Lansoprazole 30 mg daily	56	93%*	93%*	90%*
	Placebo	55	31%	27%	24%
#2	Lansoprazole 15 mg daily	50	74%*	72%*	67%*
	Lansoprazole 30 mg daily	49	75%*	72%*	55%*
	Placebo	47	16%	13%	13%

%=Life Table Estimate *(p≤0.001) versus placebo.

Regardless of initial grade of erosive esophagitis, lansoprazole 15 mg and 30 mg were similar in maintaining remission.

In a U.S., randomized, double-blind study, lansoprazole 15 mg daily (n = 100) was compared with ranitidine 150 mg twice daily (n = 106), at the recommended dosage, in patients with endoscopically-proven healed erosive esophagitis over a 12-month period. Treatment with lansoprazole resulted in patients remaining healed (Grade 0 lesions) of erosive esophagitis for significantly longer periods of time than those treated with ranitidine (p<0.001). In addition, lansoprazole was significantly more effective than ranitidine in providing complete relief of both daytime and nighttime heartburn. Patients treated with lansoprazole remained asymptomatic for a significantly longer period of time than patients treated with ranitidine [see Indications and Usage ( 1.9)].

14.10 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

In open studies of 57 patients with pathological hypersecretory conditions, such as Zollinger-Ellison syndrome (ZES) with or without multiple endocrine adenomas, lansoprazole significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia and pain. Doses ranging from 15 mg every other day to 180 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 ( 2.1)]. Lansoprazole was well tolerated at these high dose levels for prolonged periods (greater than four years in some patients). In most ZES patients, serum gastrin levels were not modified by lansoprazole. However, in some patients, serum gastrin increased to levels greater than those present prior to initiation of lansoprazole therapy [see Indications and Usage ( 1.10)]