PREVACID(lansoprazole)Delayed-Release CapsulesPREVACID(lansoprazole)For Delayed-Release Oral SuspensionPREVACID SoluTab(lansoprazole)Delayed-Release Orally Disintegrating Tablets Drug Inf...
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`PREVACID®
`(lansoprazole)
`Delayed-Release Capsules
`PREVACID®
`(lansoprazole)
`For Delayed-Release Oral Suspension
`PREVACID® SoluTab™
`(lansoprazole)
`Delayed-Release Orally Disintegrating Tablets
`DESCRIPTION
`
`The active ingredient in PREVACID® Delayed-Release Capsules, PREVACID® for Delayed-Release Oral Suspension and
`PREVACID® SoluTab™ Delayed-Release Orally Disintegrating Tablets is lansoprazole, a substituted benzimidazole, 2-[[[3-
`methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl] sulfinyl] benzimidazole, a compound that inhibits gastric acid secretion.
`Its empirical formula is C16H14F3N3O2S with a molecular weight of 369.37. PREVACID has the following structure:
`
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`
`Lansoprazole is a white to brownish-white odorless crystalline powder which melts with decomposition at approximately
`166°C. Lansoprazole is freely soluble in dimethylformamide; soluble in methanol; sparingly soluble in ethanol; slightly soluble
`in ethyl acetate, dichloromethane and acetonitrile; very slightly soluble in ether; and practically insoluble in hexane and water.
`
`Lansoprazole is stable when exposed to light for up to two months. The rate of degradation of the compound in aqueous
`solution increases with decreasing pH. The degradation half-life of the drug substance in aqueous solution at 25°C is
`approximately 0.5 hour at pH 5.0 and approximately 18 hours at pH 7.0.
`
`PREVACID is supplied in delayed-release capsules, in delayed-release orally disintegrating tablets for oral administration and
`in a packet for delayed-release oral suspension.
`
`The delayed-release capsules are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per capsule. Each
`delayed-release capsule contains enteric-coated granules consisting of 15 mg or 30 mg of lansoprazole (active ingredient)
`and the following inactive ingredients: hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, colloidal silicon
`dioxide, magnesium carbonate, methacrylic acid copolymer, starch, talc, sugar sphere, sucrose, polyethylene glycol,
`polysorbate 80, and titanium dioxide. Components of the gelatin capsule include gelatin, titanium dioxide, D&C Red No. 28,
`FD&C Blue No. 1, FD&C Green No. 3PREVACID 15-mg capsules only., and FD&C Red No. 40 (inactive ingredients).
`
`PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets are available in two dosage strengths: 15 mg and 30 mg
`of lansoprazole per tablet. Each delayed-release orally disintegrating tablet contains enteric-coated microgranules consisting
`of 15 mg or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: lactose monohydrate,
`microcrystalline cellulose, magnesium carbonate, hydroxypropyl cellulose, hypromellose, titanium dioxide, talc, mannitol,
`methacrylic acid, polyacrylate, polyethylene glycol, glyceryl monostearate, polysorbate 80, triethyl citrate, ferric oxide, citric
`acid, crospovidone, aspartamePhenylketonurics: Contains Phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg
`Tablet., artificial strawberry flavor and magnesium stearate.
`
`PREVACID for Delayed-Release Oral Suspension are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per
`packet. Each packet of delayed-release oral suspension contains enteric-coated granules consisting of 15 or 30 mg of
`lansoprazole (active ingredient) and the following inactive ingredients (inactive granules): confectioner's sugar, mannitol,
`docusate sodium, ferric oxide, colloidal silicon dioxide, xanthan gum, crospovidone, citric acid, sodium citrate, magnesium
`stearate, and artificial strawberry flavor. The lansoprazole granules and inactive granules, present in unit dose packets, are
`constituted with water to form a suspension and consumed orally.
`CLINICAL PHARMACOLOGY
`
`Pharmacokinetics and Metabolism
`
`PREVACID Delayed-Release Capsules, PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets and PREVACID for
`Delayed-Release Oral Suspension contain an enteric-coated granule formulation of lansoprazole. Absorption of lansoprazole
`begins only after the granules leave the stomach. Absorption is rapid, with mean peak plasma levels of lansoprazole
`occurring after approximately 1.7 hours. After a single-dose administration of 15 mg to 60 mg of oral lansoprazole, the peak
`plasma concentrations (Cmax) of lansoprazole and the area under the plasma concentration curves (AUCs) of lansoprazole
`were approximately proportional to the administered dose. Lansoprazole does not accumulate and its pharmacokinetics are
`unaltered by multiple dosing.
`Bass and Spangenberg
`Exhibit 1004
`http://www.medicineonline.com/...REVACID-lansoprazole-For-Delayed-Release-Oral-SuspensionPREVACID-SoluTab-lansoprazole-Delayed-Release-Orally-Disintegrating-Tablets.html[10/5/2015 1:50:42 PM]
`
`

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`PREVACID(lansoprazole)Delayed-Release CapsulesPREVACID(lansoprazole)For Delayed-Release Oral SuspensionPREVACID SoluTab(lansoprazole)Delayed-Release Orally Disintegrating Tablets Drug Inf...
`
`Special Populations
`
`Pharmacodynamics
`
`Microbiology
`
`Lansoprazole, clarithromycin and/or amoxicillin 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.
`
`CLINICAL STUDIES
`
`Duodenal Ulcer
`
`In a U.S. multicenter, double-blind, placebo-controlled, dose-response (15, 30, and 60 mg of PREVACID 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 PREVACID than with placebo. There was no evidence of a greater or earlier
`response with the two higher doses compared with PREVACID 15 mg. Based on this study and the second study described
`below, the recommended dose of PREVACID in duodenal ulcer is 15 mg per day (Table 4).
`
`Table 4: Duodenal Ulcer Healing Rates
`
`PREVACID
`15 mg daily
`(N=68)
`42.4%(p≤0.001) versus placebo.
`89.4%
`
`Week
`2
`4
`
`30 mg daily
`(N=74)
`35.6%
`91.7%
`
`60 mg daily
`(N=70)
`39.1%
`89.9%
`
`Placebo
`
`(N=72)
`11.3%
`46.1%
`
`PREVACID 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 PREVACID
`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 PREVACID than with placebo.
`There was no evidence of a greater or earlier response with the higher dose of PREVACID. Although the 15 mg dose of
`PREVACID was superior to ranitidine at 4 weeks, the lack of significant difference at 2 weeks and the absence of a difference
`between 30 mg of PREVACID and ranitidine leaves the comparative effectiveness of the two agents undetermined (Table 5).
`
`Table 5: Duodenal Ulcer Healing Rates
`
`PREVACID
`15 mg daily
`Week (N=80)
`2
`35.0%
`4
`92.3%(p≤0.05) versus placebo and ranitidine.
`
`30 mg daily
`(N=77)
`44.2%
`80.3%(p≤0.05) versus placebo.
`
`Ranitidine
`300 mg h.s.
`(N=82)
`30.5%
`70.5%
`
`Placebo
`
`(N=41)
`34.2%
`47.5%
`
`H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
`
`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 PREVACID in combination with amoxicillin
`capsules and clarithromycin tablets as triple 14-day therapy or in combination with amoxicillin capsules 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:
`
`Dual therapy:
`
`PREVACID 30 mg b.i.d./
`amoxicillin 1 gm b.i.d./
`clarithromycin 500 mg b.i.d.
`PREVACID 30 mg t.i.d./
`amoxicillin 1 gm t.i.d.
`
`All treatments were for 14 days. H. pylori eradication was defined as two negative tests (culture and histology) at 4-6 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 PREVACID 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 6 and 7).
`
`Table 6
`H. pylori Eradication Rates – Triple Therapy
`(PREVACID/amoxicillin/clarithromycin)
`Percent of Patients Cured
`[95% Confidence Interval]
`(Number of patients)
`Triple Therapy
`Evaluable AnalysisBased
`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,
`
`Triple Therapy
`Intent-to-Treat
`AnalysisPatients 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.
`
`http://www.medicineonline.com/...REVACID-lansoprazole-For-Delayed-Release-Oral-SuspensionPREVACID-SoluTab-lansoprazole-Delayed-Release-Orally-Disintegrating-Tablets.html[10/5/2015 1:50:42 PM]
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`PREVACID(lansoprazole)Delayed-Release CapsulesPREVACID(lansoprazole)For Delayed-Release Oral SuspensionPREVACID SoluTab(lansoprazole)Delayed-Release Orally Disintegrating Tablets Drug Inf...
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`Study
`
`M93-131
`
`M95-392
`
`M95-399The 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.
`
`Study
`
`M93-131
`
`M93-125
`
`Duration
`
`14 days
`
`14 days
`
`14 days
`
`10 days
`
`they were included in the
`evaluable analysis as
`failures of therapy.
`92(p<0.05) versus
`PREVACID/amoxicillin and
`PREVACID/clarithromycin dual
`therapy
`[80.0-97.7]
`(N=48)
`86(p<0.05) versus
`clarithromycin/amoxicillin dual
`therapy
`[75.7-93.6]
`(N=66)
`85
`[77.0-91.0]
`(N=113)
`84
`[76.0-89.8]
`(N=123)
`Table 7
`H. pylori Eradication Rates – 14-Day Dual Therapy
`(PREVACID/amoxicillin)
`Percent of Patients Cured
`[95% Confidence Interval]
`(Number of patients)
`Dual Therapy
`Evaluable AnalysisBased 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.
`77(p<0.05) versus PREVACID alone.
`[62.5-87.2]
`(N=51)
`66 (p<0.05) versus PREVACID alone or
`amoxicillin alone.
`[51.9-77.5]
`(N=58)
`
`86
`[73.3-93.5]
`(N=55)
`
`83
`[72.0-90.8]
`(N=70)
`
`82
`[73.9-88.1]
`(N=126)
`81
`[73.9-87.6]
`(N=135)
`
`Dual Therapy
`Intent-to-Treat AnalysisPatients
`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.
`
`70
`[56.8-81.2]
`(N=60)
`
`61
`[48.5-72.9]
`(N=67)
`
`Long-Term Maintenance Treatment of Duodenal Ulcers
`
`PREVACID 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 PREVACID
`than in patients treated with placebo over a 12-month period (Table 8).
`
`Trial Drug
`#1
`PREVACID 15 mg daily
`Placebo
`PREVACID 30 mg daily
`PREVACID 15 mg daily
`Placebo
`%=Life Table Estimate
`
`#2
`
`Table 8: Endoscopic Remission Rates
`Percent in Endoscopic Remission
`0-3 mo.
`90%(p≤0.001) versus placebo.
`49%
`94%
`87%
`33%
`
`No. of Pts.
`86
`83
`18
`15
`15
`
`0-6 mo.
`87%
`41%
`94%
`79%
`0%
`
`0-12 mo.
`84%
`39%
`85%
`70%*
`0%
`
`In trial #2, no significant difference was noted between PREVACID 15 mg and 30 mg in maintaining remission.
`
`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 PREVACID 15 mg and 30 mg once a
`day than with placebo (Table 9).
`
`Table 9: Gastric Ulcer Healing Rates
`
`PREVACID
`15 mg daily
`(N=65)
`64.6%(p≤0.05) versus
`placebo.
`92.2%
`
`30 mg daily
`(N=63)
`
`58.1%
`
`96.8%
`
`Week
`
`4
`
`8
`
`60 mg daily
`(N=61)
`
`53.3%
`
`93.2%
`
`Placebo
`
`(N=64)
`
`37.5%
`
`76.7%
`
`Patients treated with any PREVACID 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 PREVACID 30 mg was provided by a meta-analysis of published and
`unpublished data.
`
`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 8 weeks was
`statistically significantly higher with 30 mg of PREVACID 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%
`
`http://www.medicineonline.com/...REVACID-lansoprazole-For-Delayed-Release-Oral-SuspensionPREVACID-SoluTab-lansoprazole-Delayed-Release-Orally-Disintegrating-Tablets.html[10/5/2015 1:50:42 PM]
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`PREVACID(lansoprazole)Delayed-Release CapsulesPREVACID(lansoprazole)For Delayed-Release Oral SuspensionPREVACID SoluTab(lansoprazole)Delayed-Release Orally Disintegrating Tablets Drug Inf...
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`female patients and 33% male patients. Race was distributed as follows: 87% Caucasian, 8% Black, 5% other. There was no
`statistically significant difference between PREVACID 30 mg daily and the active control on symptom relief (i.e., abdominal
`pain) (Table 10).
`
`Table 10: NSAID-Associated Gastric Ulcer Healing RatesActual observed ulcer(s) healed at time points ± 2 days
`Study #1
`PREVACID
`30 mg daily
`Week 4 60% (53/88) (p≤0.05) versus the active control
`Week 8 79% (62/79)
`Study #2
`PREVACID
`30 mg daily
`Week 4 53% (40/75)
`Week 8 77% (47/61)
`
`28% (23/83)
`55% (41/74)
`
`Active Control
`
`38% (31/82)
`50% (33/66)
`
`Active Control Dose for healing of gastric ulcer
`
`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 4, 8, and 12 weeks was significantly higher with
`15 or 30 mg of PREVACID 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 PREVACID demonstrated no additional
`benefit in risk reduction of the NSAID-associated gastric ulcer than the 15 mg dose (Table 11).
`
`Table 11: Proportion of Patients Remaining Free of Gastric Ulcers% = Life Table
`Estimate
`(p<0.001) PREVACID 15 mg daily versus placebo; PREVACID 30 mg daily versus
`placebo; and misoprostol 200 µg q.i.d. versus placebo.
`(p<0.05) Misoprostol 200 µg q.i.d. versus PREVACID 15 mg daily; and misoprostol 200
`µg q.i.d. versus PREVACID 30 mg daily
`PREVACID
`PREVACID
`Misoprostol
`15 mg daily
`30 mg daily
`200 µg q.i.d.
`(N=121)
`(N=116)
`(N=106)
`90%
`92%
`96%
`86%
`88%
`95%
`80%
`82%
`93%
`
`Placebo
`
`(N=112)
`66%
`60%
`51%
`
`Week
`4
`8
`12
`
`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 8 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 8-week treatment period are presented in Table 12 and in Figures 1 and 2:
`
`Table 12: Frequency of Heartburn
`PREVACID 15 mg
`(n=80)
`
`PREVACID 30 mg
`(n=86)
`
`71%(p<0.01) versus
`placebo.
`81%
`84%
`
`86%
`89%
`92%
`
`46%
`
`76%
`82%
`
`57%
`73%
`80%
`
`Variable
`
`Placebo
`(n=43)
`
` Median
`
`% of Days without Heartburn
`
`Week 1
`
`Week 4
`Week 8
`% of Nights without Heartburn
`Week 1
`Week 4
`Week 8
`
`0%
`
`11%
`13%
`
`17%
`25%
`36%
`
`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 (b.i.d.) in decreasing the
`frequency and severity of day and night heartburn associated with GERD for the 8-week treatment period. No significant
`additional benefit from lansoprazole 30 mg once daily was observed.
`
`Long-Term Maintenance Treatment 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 PREVACID than in patients treated with placebo over a 12-month period (Table
`16).
`
`Trial
`
`Drug
`
`Table 16: Endoscopic Remission Rates
`Percent in Endoscopic Remission
`0-3 mo.
`0-6 mo.
`83%(p≤0.001)
`
`No. of Pts.
`
`0-12 mo.
`
`http://www.medicineonline.com/...REVACID-lansoprazole-For-Delayed-Release-Oral-SuspensionPREVACID-SoluTab-lansoprazole-Delayed-Release-Orally-Disintegrating-Tablets.html[10/5/2015 1:50:42 PM]
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`PREVACID(lansoprazole)Delayed-Release CapsulesPREVACID(lansoprazole)For Delayed-Release Oral SuspensionPREVACID SoluTab(lansoprazole)Delayed-Release Orally Disintegrating Tablets Drug Inf...
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`#1
`
`PREVACID 15 mg daily
`
`#2
`
`PREVACID 30 mg daily
`Placebo
`PREVACID 15 mg daily
`PREVACID 30 mg daily
`Placebo
`%=Life Table Estimate
`
`59
`
`56
`55
`50
`49
`47
`
`versus placebo.
`93%
`31%
`74%
`75%
`16%
`
`81%
`
`93%
`27%
`72%
`72%
`13%
`
`79%
`
`90%
`24%
`67%
`55%
`13%
`
`Regardless of initial grade of erosive esophagitis, PREVACID 15 mg and 30 mg were similar in maintaining remission.
`
`In a U.S., randomized, double-blind, study, PREVACID 15 mg daily (n = 100) was compared with ranitidine 150 mg b.i.d. (n
`= 106), at the recommended dosage, in patients with endoscopically-proven healed erosive esophagitis over a 12-month
`period. Treatment with PREVACID 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, PREVACID was significantly
`more effective than ranitidine in providing complete relief of both daytime and nighttime heartburn. Patients treated with
`PREVACID remained asymptomatic for a significantly longer period of time than patients treated with ranitidine.
`
`Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
`
`In open studies of 57 patients with pathological hypersecretory conditions, such as Zollinger-Ellison (ZE) syndrome with or
`without multiple endocrine adenomas, PREVACID 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). PREVACID was well tolerated at these high dose levels for prolonged periods (greater
`than four years in some patients). In most ZE patients, serum gastrin levels were not modified by PREVACID. However, in
`some patients, serum gastrin increased to levels greater than those present prior to initiation of lansoprazole therapy.
`
`INDICATIONS AND USAGE
`
`PREVACID Delayed-Release Capsules, PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets and PREVACID For
`Delayed-Release Oral Suspension are indicated for:
`
`Short-Term Treatment of Active Duodenal Ulcer
`
`PREVACID is indicated for short-term treatment (for 4 weeks) for healing and symptom relief of active duodenal ulcer.
`
`H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
`
`Maintenance of Healed Duodenal Ulcers
`
`PREVACID is indicated to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months.
`
`Short-Term Treatment of Active Benign Gastric Ulcer
`
`PREVACID is indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of active benign gastric ulcer.
`
`Healing of NSAID-Associated Gastric Ulcer
`
`PREVACID is indicated for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled
`studies did not extend beyond 8 weeks.
`
`Risk Reduction of NSAID-Associated Gastric Ulcer
`
`PREVACID is indicated for reducing the risk of NSAID-associated gastric ulcers in patients with a history of a documented
`gastric ulcer who require the use of an NSAID. Controlled studies did not extend beyond 12 weeks.
`
`Gastroesophageal Reflux Disease (GERD)
`
`Maintenance of Healing of Erosive Esophagitis
`
`PREVACID is indicated to maintain healing of erosive esophagitis. Controlled studies did not extend beyond 12 months.
`
`Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
`
`PREVACID is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison
`syndrome.
`
`CONTRAINDICATIONS
`
`PREVACID is contraindicated in patients with known severe hypersensitivity to any component of the formulation of
`PREVACID.
`
`Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin.
`
`Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, and any of the
`macrolide antibiotics.
`
`Concomitant administration of clarithromycin and any of the following drugs is contraindicated: cisapride, pimozide,
`astemizole, terfenadine, ergotamine or dihydroergotamine. There have been post-marketing reports of drug interactions
`when clarithromycin and/or erythromycin are co-administered with cisapride, pimozide, astemizole, or terfenadine resulting
`in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely
`due to inhibition of metabolism of these drugs by erythromycin and clarithromycin. Fatalities have been reported.
`
`For information about contraindications of other drugs that may be used in combination with amoxicillin or clarithromycin,
`refer to the CONTRAINDICATIONS section of their package inserts.
`
`Please refer to full prescribing information for amoxicillin and clarithromycin before prescribing.
`
`WARNINGS
`
`http://www.medicineonline.com/...REVACID-lansoprazole-For-Delayed-Release-Oral-SuspensionPREVACID-SoluTab-lansoprazole-Delayed-Release-Orally-Disintegrating-Tablets.html[10/5/2015 1:50:42 PM]
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`PREVACID(lansoprazole)Delayed-Release CapsulesPREVACID(lansoprazole)For Delayed-Release Oral SuspensionPREVACID SoluTab(lansoprazole)Delayed-Release Orally Disintegrating Tablets Drug Inf...
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`CLARITHROMYCIN SHOULD NOT BE USED IN PREGNANT WOMEN EXCEPT IN CLINICAL CIRCUMSTANCES WHERE NO
`ALTERNATIVE THERAPY IS APPROPRIATE. IF PREGNANCY OCCURS WHILE TAKING CLARITHROMYCIN, THE PATIENT
`SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS (see WARNINGS in the prescribing information for
`clarithromycin).
`
`Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin and amoxicillin,
`and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who
`present with diarrhea subsequent to the administration of antibacterial agents.
`
`Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies
`indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis."
`
`After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases
`of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases,
`consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an
`antibacterial drug clinically effective against Clostridium difficile colitis.
`
`There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine,
`especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such
`patients.
`
`Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy.
`These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity
`to multiple allergens.
`
`There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have
`experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with any penicillin,
`careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other
`allergens. If an allergic reaction occurs, amoxicillin should be discontinued and the appropriate therapy instituted.
`
`SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN,
`INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS
`INDICATED.
`
`For information about warnings of other drugs that may be used in combination with amoxicillin or clarithromycin, refer to
`the WARNINGS section of their package inserts.
`PRECAUTIONS
`
`General
`
`Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.
`
`For information about precautions of other drugs that may be used in combination with amoxicillin or clarithromycin, refer to
`the PRECAUTIONS section of their package inserts.
`
`Information For Patients
`
`PREVACID is available as a capsule, orally disintegrating tablet and oral suspension, and is available in 15 mg and 30 mg
`strengths. Directions for use specific to the route and available methods of administration for each of these dosage forms is
`presented below. PREVACID should be taken before eating. PREVACID products SHOULD NOT BE CRUSHED OR CHEWED.
`
`Phenylketonurics: Contains Phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg Tablet.
`
`Drug Interactions
`
`Lansoprazole is metabolized through the cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes.
`Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the
`cytochrome P450 system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone,
`diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P450
`isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. When lansoprazole was administered concomitantly with
`theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small
`magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern.
`Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole is started or
`stopped to ensure clinically effective blood levels.
`
`In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected
`following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International
`Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and
`warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients
`treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and
`prothrombin time.
`
`In an open-label, single-arm, eight-day, pharmacokinetic study of 28 adult rheumatoid arthritis patients (who required the
`chronic use of 7.5 to 15 mg of methotrexate given weekly), administration of 7 days of naproxen 500 mg BID and
`lansoprazole 30 mg daily had no effect on the pharmacokinetics of methotrexate and 7-hydroxymethotrexate. While this
`study was not designed to assess the safety of this combination of drugs, no major adverse events were noted.
`
`Lansoprazole has also been shown to have no clinically significant interaction with amoxicillin.
`
`In a single-dose crossover study examining lansoprazole 30 mg and omeprazole 20 mg each administered alone and
`concomitantly with sucralfate 1 gram, absorption of the proton pump inhibitors was delayed and their bioavailability was
`reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors
`should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with
`PREVACID and there was no evidence of a change in the efficacy of PREVACID.
`
`Lansoprazole causes a profound and long-lasting inhibition of gastric acid secretion; therefore, it is theoretically possible that
`lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g.,
`ketoconazole, ampicillin esters, iron salts, digoxin).
`
`Carcinogenesis, Mutagenesis, Impairment Of Fertility
`
`In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated with oral lansoprazole doses of 5 to 150
`mg/kg/day - about 1 to 40 times the exposure on a body surface (mg/m2) basis, of a 50-kg person of average height [1.46
`m2 body surface area (BSA)] given the recommended human dose of 30 mg/day (22.2 mg/m2). Lansoprazole produced
`dose-related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. It also
`increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats, lansoprazole produced a
`dose-related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15
`to 150 mg/kg/day (4 to 40 times the recommended human dose based on BSA) exceeded the low background incidence
`(range = 1.4 to