Prevacid

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 and in delayed-release orally disintegrating tablets for oral administration.

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: sugar sphere, sucrose, methacrylic acid copolymer, low substituted hydroxypropyl cellulose, starch, magnesium carbonate, talc, polyethylene glycol, titanium dioxide, polysorbate 80, hydroxypropyl cellulose, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, FD&C Green No. 3 PREVACID 15-mg capsules only. , and FD&C Red No. 40.

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: mannitol, methacrylic acid, hydroxypropyl cellulose, lactose monohydrate-microcrystalline cellulose sphere, triethyl citrate, crospovidone, polyacrylate, magnesium carbonate, aspartame Phenylketonurics : Contains Phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg Tablet. , glyceryl monostearate, hypromellose, magnesium stearate, citric acid, titanium dioxide, talc, artificial strawberry flavor, polyethylene glycol, polysorbate 80 and ferric oxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

PREVACID (lansoprazole) belongs to a class of antisecretory 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 parietal cell, lansoprazole 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 gastric acid secretion irrespective of the stimulus. Lansoprazole does not exhibit anticholinergic or histamine type-2 antagonist activity.

12.2 Pharmacodynamics

Antisecretory Activity: After oral administration, lansoprazole was shown to significantly decrease the basal acid output and significantly increase the mean gastric pH and percent of time the gastric pH was greater than 3 and greater than 4. Lansoprazole also significantly reduced meal-stimulated gastric acid output and secretion volume, as well as pentagastrin-stimulated acid output. In patients with hypersecretion of acid, lansoprazole significantly reduced basal and pentagastrin-stimulated gastric acid secretion. Lansoprazole inhibited the normal increases in secretion volume, acidity and acid output induced by insulin.

The intragastric pH results of a five-day, pharmacodynamic, crossover study of 15 mg and 30 mg of once daily lansoprazole are presented in Table 4:

After the initial dose in this study, increased gastric pH was seen within 1 to 2 hours with 30 mg of lansoprazole and 2 to 3 hours with 15 mg of lansoprazole. After multiple daily dosing, increased gastric pH was seen within the first hour post-dosing with 30 mg of lansoprazole and within 1 to 2 hours post-dosing with 15 mg of lansoprazole.

Acid suppression may enhance the effect of antimicrobials in eradicating Helicobacter pylori (H. pylori). The percentage of time gastric pH was elevated above 5 and 6 was evaluated in a crossover study of PREVACID given daily, twice daily and three times daily (Table 5).

The inhibition of gastric acid secretion as measured by intragastric pH gradually returned to normal over two to four days after multiple doses. There was no indication of rebound gastric acidity.

Enterochromaffin -like (ECL) Cell Effects

During lifetime exposure of rats with up to 150 mg/kg/day of lansoprazole dosed seven days per week, marked hypergastrinemia was observed followed by ECL cell proliferation and formation of carcinoid tumors, especially in female rats. Gastric biopsy specimens from the body of the stomach from approximately 150 patients treated continuously with lansoprazole for at least one year did not show evidence of ECL cell effects similar to those seen in rat studies. Longer term data are needed to rule out the possibility of an increased risk of the development of gastric tumors in patients receiving long-term therapy with lansoprazole [see Nonclinical Toxicology (13.1)].

Other Gastric Effects in Humans

Lansoprazole did not significantly affect mucosal blood flow in the fundus of the stomach. Due to the normal physiologic effect caused by the inhibition of gastric acid secretion, a decrease of about 17% in blood flow in the antrum, pylorus, and duodenal bulb was seen. Lansoprazole significantly slowed the gastric emptying of digestible solids. Lansoprazole increased serum pepsinogen levels and decreased pepsin activity under basal conditions and in response to meal stimulation or insulin injection. As with other agents that elevate intragastric pH, increases in gastric pH were associated with increases in nitrate-reducing bacteria and elevation of nitrite concentration in gastric juice in patients with gastric ulcer. No significant increase in nitrosamine concentrations was observed.

Serum Gastrin Effects

In over 2100 patients, median fasting serum gastrin levels increased 50% to 100% from baseline but remained within normal range after treatment with 15 to 60 mg of oral lansoprazole. These elevations reached a plateau within two months of therapy and returned to pretreatment levels within four weeks after discontinuation of therapy.

Endocrine Effects

Human studies for up to one year have not detected any clinically significant effects on the endocrine system. Hormones studied include testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), prolactin, cortisol, estradiol, insulin, aldosterone, parathormone, glucagon, thyroid stimulating hormone (TSH), triiodothyronine (T₃), thyroxine (T₄), and somatotropic hormone (STH). Lansoprazole in oral doses of 15 to 60 mg for up to one year had no clinically significant effect on sexual function. In addition, lansoprazole in oral doses of 15 to 60 mg for two to eight weeks had no clinically significant effect on thyroid function. In 24-month carcinogenicity studies in Sprague-Dawley rats with daily lansoprazole dosages up to 150 mg/kg, proliferative changes in the Leydig cells of the testes, including benign neoplasm, were increased compared to control rats.

Other Effects

No systemic effects of lansoprazole on the central nervous system, lymphoid, hematopoietic, renal, hepatic, cardiovascular, or respiratory systems have been found in humans. Among 56 patients who had extensive baseline eye evaluations, no visual toxicity was observed after lansoprazole treatment (up to 180 mg/day) for up to 58 months. After lifetime lansoprazole exposure in rats, focal pancreatic atrophy, diffuse lymphoid hyperplasia in the thymus, and spontaneous retinal atrophy were seen.

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 [see Indications and Usage (1.2)].

Helicobacter pylori Pretreatment Resistance

Clarithromycin pretreatment resistance (≥2.0 mcg/mL) was 9.5% (91/960) by E-test and 11.3% (12/106) by agar dilution in the dual and triple therapy clinical trials (M93-125, M93-130, M93-131, M95-392, and M95-399).

Amoxicillin pretreatment susceptible isolates (≤0.25 mcg/mL) occurred in 97.8% (936/957) and 98.0% (98/100) of the patients in the dual and triple therapy clinical trials by E-test and agar dilution, respectively. Twenty-one of 957 patients (2.2%) by E-test, and 2 of 100 patients (2.0%) by agar dilution, had amoxicillin pretreatment MICs of greater than 0.25 mcg/mL. One patient on the 14-day triple therapy regimen had an unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of greater than 256 mcg/mL by E-test and the patient was eradicated of H. pylori (Table 6).

Table 6: Clarithromycin Susceptibility Test Results and Clinical/Bacteriological Outcomes^#

Clarithromycin Pretreatment Results		Clarithromycin Post-treatment Results
		H. pylori negative - eradicated	H. pylori positive – not eradicated Post-treatment susceptibility results
		SSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	ISusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	RSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	No MIC
#Includes only patients with pretreatment clarithromycin susceptibility results
Triple Therapy 14-Day (lansoprazole 30 mg twice daily/amoxicillin 1 g twice daily/clarithromycin 500 mg twice daily) (M95-399, M93-131, M95-392)
SusceptibleSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	112	105				7
IntermediateSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	3	3
ResistantSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	17	6			7	4
Triple Therapy 10-Day (lansoprazole 30 mg twice daily/amoxicillin 1 g twice daily/clarithromycin 500 mg twice daily) (M95-399)
SusceptibleSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	42	40	1		1
IntermediateSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL
ResistantSusceptible (S) MIC ≤0.25 mcg/mL, Intermediate (I) MIC 0.5 to 1.0 mcg/mL, Resistant (R) MIC ≥2 mcg/mL	4	1			3

Patients not eradicated of H. pylori following lansoprazole/amoxicillin/clarithromycin triple therapy will likely have clarithromycin resistant H. pylori. Therefore, for those patients who fail therapy, clarithromycin susceptibility testing should be done when possible. Patients with clarithromycin resistant H. pylori should not be treated with lansoprazole/amoxicillin/clarithromycin triple therapy or with regimens which include clarithromycin as the sole antimicrobial agent.

Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes: In the dual and triple therapy clinical trials, 82.6% (195/236) of the patients that had pretreatment amoxicillin susceptible MICs (≤0.25 mcg/mL) were eradicated of H. pylori. Of those with pretreatment amoxicillin MICs of greater than 0.25 mcg/mL, three of six had the H. pylori eradicated. A total of 30% (21/70) of the patients failed lansoprazole 30 mg three times daily/amoxicillin 1 g three times daily dual therapy and a total of 12.8% (22/172) of the patients failed the 10- and 14-day triple therapy regimens. Post-treatment susceptibility results were not obtained on 11 of the patients who failed therapy. Nine of the 11 patients with amoxicillin post-treatment MICs that failed the triple therapy regimen also had clarithromycin resistant H. pylori isolates.

Susceptibility Test for Helicobacter pylori: For susceptibility testing information about Helicobacter pylori, see Microbiology section in prescribing information for clarithromycin and amoxicillin.

12.3 Pharmacokinetics

PREVACID Delayed-Release Capsules and PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets 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 (C_max) 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.

Absorption: The absorption of lansoprazole is rapid, with the mean C_max occurring approximately 1.7 hours after oral dosing, and the absolute bioavailability is over 80%. In healthy subjects, the mean (±SD) plasma half-life was 1.5 (±1.0) hours. Both the C_max and AUC are diminished by about 50% to 70% if lansoprazole is given 30 minutes after food, compared to the fasting condition. There is no significant food effect if lansoprazole is given before meals.

Distribution: Lansoprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 0.05 to 5.0 mcg/mL.

Metabolism: Lansoprazole is extensively metabolized in the liver. Two metabolites have been identified in measurable quantities in plasma (the hydroxylated sulfinyl and sulfone derivatives of lansoprazole). These metabolites have very little or no antisecretory activity. Lansoprazole is thought to be transformed into two active species which inhibit acid secretion by blocking the proton pump [(H⁺, K⁺)-ATPase enzyme system] at the secretory surface of the gastric parietal cell. The two active species are not present in the systemic circulation. The plasma elimination half-life of lansoprazole is less than 2 hours while the acid inhibitory effect lasts more than 24 hours. Therefore, the plasma elimination half-life of lansoprazole does not reflect its duration of suppression of gastric acid secretion.

Elimination: Following single-dose oral administration of PREVACID, virtually no unchanged lansoprazole was excreted in the urine. In one study, after a single oral dose of ¹⁴C-lansoprazole, approximately one-third of the administered radiation was excreted in the urine and two-thirds was recovered in the feces. This implies a significant biliary excretion of the lansoprazole metabolites.

Specific Populations

Pediatric Use:

One to 17 years of age

The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged 1 to 11 years and 12 to 17 years in two separate clinical studies. In children aged 1 to 11 years, lansoprazole was dosed 15 mg daily for subjects weighing ≤30 kg and 30 mg daily for subjects weighing greater than 30 kg. Mean C_max and AUC values observed on Day 5 of dosing were similar between the two dose groups and were not affected by weight or age within each weight-adjusted dose group used in the study. In adolescent subjects aged 12 to 17 years, subjects were randomized to receive lansoprazole at 15 mg or 30 mg daily. Mean C_max and AUC values of lansoprazole were not affected by body weight or age; and nearly dose-proportional increases in mean C_max and AUC values were observed between the two dose groups in the study. Overall, lansoprazole pharmacokinetics in pediatric patients aged 1 to 17 years were similar to those observed in healthy adult subjects.

Neonate to less than one year of age

Refer to Section 8.4 for the pharmacokinetics of lansoprazole in pediatric patients with GERD aged less than 28 days and 1 to 11 months.

Geriatric Use: The clearance of lansoprazole is decreased in the elderly, with elimination half-life increased approximately 50% to 100%. Because the mean half-life in the elderly remains between 1.9 to 2.9 hours, repeated once daily dosing does not result in accumulation of lansoprazole. Peak plasma levels were not increased in the elderly. No dosage adjustment is necessary in the elderly [see Use in Specific Populations (8.5)].

Renal Impairment: In patients with severe renal impairment, plasma protein binding decreased by 1.0% to 1.5% after administration of 60 mg of lansoprazole. Patients with renal impairment had a shortened elimination half-life and decreased total AUC (free and bound). The AUC for free lansoprazole in plasma, however, was not related to the degree of renal impairment; and the C_max and T_max (time to reach the maximum concentration) were not different than the C_max and T_max from subjects with normal renal function. No dosage adjustment is necessary in patients with renal impairment [see Use in Specific Populations (8.6)].

Hepatic Impairment: In patients with various degrees of chronic hepatic impairment, the mean plasma half-life of lansoprazole was prolonged from 1.5 hours to 3.2 to 7.2 hours. An increase in the mean AUC of up to 500% was observed at steady state in hepatically-impaired patients compared to healthy subjects. Consider dose reduction in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

Gender: In a study comparing 12 male and 6 female human subjects who received lansoprazole, no gender differences were found in pharmacokinetics and intragastric pH results [see Use in Specific Populations (8.8)].

Drug-Drug Interactions

PREVACID may interfere with the absorption of other drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).

PREVACID is metabolized through the cytochrome P₄₅₀ system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that PREVACID 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.

Atazanavir : PREVACID causes long-lasting inhibition of gastric acid secretion. PREVACID substantially decreases the systemic concentrations of the HIV protease inhibitor atazanavir, which is dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir and the development of HIV resistance. Therefore, PREVACID, or other proton pump inhibitors, should not be co-administered with atazanavir.

Theophylline : When PREVACID 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 PREVACID is started or stopped to ensure clinically effective blood levels.

Warfarin: 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 PREVACID, 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.

Methotrexate and 7-hydromethotrexate: 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 twice daily and PREVACID 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 reactions were noted. However, this study was conducted with low doses of methotrexate. A drug interaction study with high doses of methotrexate has not been conducted.

Amoxicillin: PREVACID has also been shown to have no clinically significant interaction with amoxicillin.

Sucralfate: In a single-dose crossover study examining PREVACID 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.

Clopidogrel : Clopidogrel is metabolized to its active metabolite in part by CYP2C19. A study of healthy subjects who were CYP2C19 extensive metabolizers, receiving once daily administration of clopidogrel 75 mg alone or concomitantly with PREVACID 30 mg (n=40), for 9 days was conducted. The mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (mean AUC ratio was 86%, with 90% CI of 80 to 92%) when PREVACID was coadministered compared to administration of clopidogrel alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 mcM ADP) was related to the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.

13 NONCLINICAL TOXICOLOGY

13.1 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. 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 10%) for this strain of rat.

In a 24-month carcinogenicity study, CD-1 mice were treated with oral lansoprazole doses of 15 to 600 mg/kg/day, 2 to 80 times the recommended human dose based on BSA. Lansoprazole produced a dose-related increased incidence of gastric ECL cell hyperplasia. It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 and 600 mg/kg/day (40 to 80 times the recommended human dose based on BSA) and female mice treated with 150 to 600 mg/kg/day (20 to 80 times the recommended human dose based on BSA) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg/kg/day (10 to 80 times the recommended human dose based on BSA).

A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive.

Lansoprazole was positive in the Ames test and the in vitro human lymphocyte chromosomal aberration assay. Lansoprazole was not genotoxic in the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo mouse micronucleus test, or the rat bone marrow cell chromosomal aberration test.

Lansoprazole at oral doses up to 150 mg/kg/day (40 times the recommended human dose based on BSA) was found to have no effect on fertility and reproductive performance of male and female rats.

13.2 Animal Toxicology and/or Pharmacology

Reproductive Toxicology Studies

Reproduction studies have been performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day [40 times the recommended human dose (30 mg/day) based on body surface area (BSA)] and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on BSA) and have revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole.

14 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 7).

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 8) [see Indications and Usage (1.1)].

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:

All treatments were for 14 days. H. pylori eradication was defined as two negative tests (culture and histology) at 4 to 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 9 and 10) [see Indications and Usage (1.2)].

Table 9 H. pylori Eradication Rates – Triple Therapy (PREVACID/amoxicillin/clarithromycin) Percent of Patients Cured [95% Confidence Interval] (Number of patients)

Study	Duration	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, they were included in the evaluable analysis as failures of therapy.	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.
M93-131	14 days	92(p<0.05) versus PREVACID/amoxicillin and PREVACID/clarithromycin dual therapy. [80.0-97.7] (N=48)	86(p<0.05) versus PREVACID/amoxicillin and PREVACID/clarithromycin dual therapy. [73.3-93.5] (N=55)
M95-392	14 days	86(p<0.05) versus clarithromycin/amoxicillin dual therapy. [75.7-93.6] (N=66)	83(p<0.05) versus clarithromycin/amoxicillin dual therapy. [72.0-90.8] (N=70)
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.	14 days	85 [77.0-91.0] (N=113)	82 [73.9-88.1] (N=126)
	10 days	84 [76.0-89.8] (N=123)	81 [73.9-87.6] (N=135)

Table 10 H. pylori Eradication Rates – 14-Day Dual Therapy (PREVACID/amoxicillin) Percent of Patients Cured [95% Confidence Interval] (Number of patients)

Study	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.	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.
M93-131	77(p<0.05) versus PREVACID alone. [62.5-87.2] (N=51)	70(p<0.05) versus PREVACID alone. [56.8-81.2] (N=60)
M93-125	66(p<0.05) versus PREVACID alone or amoxicillin alone. [51.9-77.5] (N=58)	61(p<0.05) versus PREVACID alone or amoxicillin alone. [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 11) [see Indications and Usage (1.3)].

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 12) [see Indications and Usage (1.4)].

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% 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 13) [see Indications and Usage (1.5)].

Table 13: NSAID-Associated Gastric Ulcer Healing RatesActual observed ulcer(s) healed at time points ± 2 days

Study #1
	PREVACID 30 mg daily	Active ControlDose for healing of gastric ulcer
Week 4	60% (53/88) (p≤0.05) versus the active control	28% (23/83)
Week 8	79% (62/79) (p≤0.05) versus the active control	55% (41/74)
Study #2
	PREVACID 30 mg daily	Active ControlDose for healing of gastric ulcer
Week 4	53% (40/75)	38% (31/82)
Week 8	77% (47/61) (p≤0.05) versus the active control	50% (33/66)

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 14) [see Indications and Usage (1.6)].

Table 14: Proportion of Patients Remaining Free of Gastric Ulcers% = Life Table Estimate

Week	PREVACID 15 mg daily (N=121)	PREVACID 30 mg daily (N=116)	Misoprostol 200 mcg four times daily (N=106)	Placebo (N=112)
4	90%	92%	96%	66%
8	86%	88%	95%	60%
12	80%	82%	93%	51%
(p<0.001) PREVACID 15 mg daily versus placebo; PREVACID 30 mg daily versus placebo; and misoprostol 200 mcg four times daily versus placebo.
(p<0.05) Misoprostol 200 mcg four times daily versus PREVACID 15 mg daily; and misoprostol 200 mcg four times daily versus PREVACID 30 mg daily.

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 15 and in Figures 1 and 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 8-week treatment period. No significant additional benefit from lansoprazole 30 mg once daily was observed [see Indications and Usage (1.7)].

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 2 or more and grades 3 and 4 signifying erosive disease, the percentages of patients with healing are presented in Table 16:

In this study, all PREVACID 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.

PREVACID was also compared in a U.S. multicenter, double-blind study to a low dose of ranitidine in 242 patients with erosive reflux esophagitis. PREVACID at a dose of 30 mg was significantly more effective than ranitidine 150 mg twice daily as shown below (Table 17).

In addition, patients treated with PREVACID 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 PREVACID 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, PREVACID produced healing rates similar to those shown above.

In a U.S. multicenter, double-blind, active-controlled study, 30 mg of PREVACID 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. PREVACID 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 PREVACID, as all patients had demonstrated unresponsiveness to the histamine H₂-receptor antagonist mode of treatment. It does indicate, however, that PREVACID may be useful in patients failing on a histamine H₂-receptor antagonist (Table 18) [see Indications and Usage (1.7)].

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 19).

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 twice daily (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 [see Indications and Usage (1.8)].

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, 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 (2.1)]. PREVACID 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 PREVACID. However, in some patients, serum gastrin increased to levels greater than those present prior to initiation of lansoprazole therapy [see Indications and Usage (1.9)].

15 REFERENCES

1. National Committee for Clinical Laboratory Standards. Summary Minutes, Subcommittee on Antimicrobial Susceptibility Testing, Tampa, FL, January 11-13, 1998.

16 HOW SUPPLIED/STORAGE AND HANDLING

PREVACID Delayed-Release Capsules, 15 mg, are opaque, hard gelatin, colored pink and green with "TAP" and "PREVACID 15" imprinted on the capsules. The 30 mg capsules are opaque, hard gelatin, colored pink and black with "TAP" and "PREVACID 30" imprinted on the capsules. They are available as follows:

PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets, 15 mg, are white to yellowish white uncoated tablets with orange to dark brown speckles, with "15" debossed on one side of the tablet. The 30 mg are white to yellowish white uncoated tablets with orange to dark brown speckles, with "30" debossed on one side of the tablet. The tablets are available as follows:

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)[see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

[See FDA-Approved Medication Guide and Patient Instructions for Use]

Patient should be informed of the following:

• •Advise patients to immediately report and seek care for diarrhea that does not improve. This may be a sign of Clostridium difficile associated diarrhea [see Warnings and Precautions (5.2)].
• •Advise patients to immediately report and seek care for any cardiovascular or neurological symptoms including palpitations, dizziness, seizures, and tetany as these may be signs of hypomagnesemia [see Warnings and Precautions (5.4) ].

Information for Patients

PREVACID is available as a capsule and an orally disintegrating tablet, 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 [see Dosage and Administration (2.3)].

• • 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.

Administration Options

1. PREVACID Delayed-Release Capsules – Oral Administration

• •PREVACID Delayed-Release Capsules should be swallowed whole.
• •Alternatively, for patients who have difficulty swallowing capsules, PREVACID Delayed-Release Capsules can be opened and administered as follows:
  • ∘Open capsule.
  • ∘Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
  • ∘Swallow immediately.
• •PREVACID Delayed-Release Capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows:
  • ∘Open capsule.
  • ∘Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately 2 ounces).
  • ∘Mix briefly.
  • ∘Swallow immediately.
  • ∘To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.

PREVACID Delayed-Release Capsules – Nasogastric Tube (≥16 French) Administration

• •For patients who have a nasogastric tube in place, PREVACID Delayed-Release Capsules can be administered as follows:
  • ∘Open capsule.
  • ∘Mix intact granules into 40 mL of apple juice. DO NOT USE OTHER LIQUIDS.
  • ∘Inject through the nasogastric tube into the stomach.
  • ∘Flush with additional apple juice to clear the tube.

USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.

2. PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets

• •PREVACID SoluTab should not be broken or cut.
• •PREVACID SoluTab should not be chewed.
  • ∘Place the tablet on the tongue and allow it to disintegrate, with or without water, until the particles can be swallowed.
  • ∘The tablet typically disintegrates in less than 1 minute.
  • ∘Alternatively, for children or other patients who have difficulty swallowing tablets, PREVACID SoluTab can be delivered in two different ways.
•   PREVACID SoluTab – Oral Syringe
  •  For administration via oral syringe, PREVACID SoluTab can be administered as follows:
    • ▪Place a 15 mg tablet in oral syringe and draw up 4 mL of water, or place a 30 mg tablet in oral syringe and draw up 10 mL of water.
    • ▪Shake gently to allow for a quick dispersal.
    • ▪After the tablet has dispersed, administer the contents within 15 minutes.
    • ▪Refill the syringe with approximately 2 mL (5 mL for the 30 mg tablet) of water, shake gently, and administer any remaining contents.
•   PREVACID SoluTab – Nasogastric Tube (≥8 French) Administration
  •  For administration via a nasogastric tube, PREVACID SoluTab can be administered as follows:
    • ▪Place a 15 mg tablet in a syringe and draw up 4 mL of water, or place a 30 mg tablet in a syringe and draw up 10 mL of water.
    • ▪Shake gently to allow for a quick dispersal.
    • ▪After the tablet has dispersed, inject through the nasogastric tube into the stomach within 15 minutes.
    • ▪Refill the syringe with approximately 5 mL of water, shake gently, and flush the nasogastric tube.

MEDICATION GUIDE

PREVACID ( prev -a- sid )
( lansoprazole )
Delayed-Release Capsules
and
PREVACID SoluTab ( prev -a- sid sol-u-tab)
( lansoprazole )
Delayed-Release Orally Disintegrating Tablets

Read this Medication Guide before you start taking PREVACID and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information that I should know about PREVACID?

PREVACID may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

PREVACID can cause serious side effects, including:

• • Diarrhea. PREVACID may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection (Clostridium difficile) in your intestines.

Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.

• • Bone fractures. People who take multiple daily doses of proton pump inhibitor medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist or spine. You should take PREVACID exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take PREVACID.

PREVACID can have other serious side effects. See “What are the possible side effects of PREVACID?”

What is PREVACID?

PREVACID is a prescription medicine called a proton pump inhibitor (PPI). PREVACID reduces the amount of acid in your stomach.

PREVACID is used in adults:

• •for 4 weeks for the healing and symptom relief of duodenal ulcers. The duodenal area is the area where food passes when it leaves the stomach.
• •with certain antibiotics to treat an infection called H. pylori. Sometimes H. pylori bacteria can cause duodenal ulcers. The infection needs to be treated to prevent ulcers from coming back.
• •for continued healing of duodenal ulcers.
• •for up to 8 weeks to heal stomach ulcers.
• •for up to 8 weeks to heal stomach ulcers in some people taking pain medicines called non-steroidal anti-inflammatory drugs (NSAIDs).
• •for reducing the risk of stomach ulcers in some people taking NSAIDs.
• •for up to 8 weeks for the relief of heartburn and other symptoms of gastroesophageal reflux disease (GERD).
  GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour taste or burping.
• •for 8 weeks to heal the acid-related damage to the lining of the esophagus (called erosive esophagitis) and to relieve symptoms. If needed, your doctor may prescribe another 8 weeks of PREVACID.
• •for continued healing of erosive esophagitis.
• •for the long-term treatment of conditions where your stomach makes too much acid. This includes a condition called Zollinger-Ellison syndrome.

PREVACID is used in children and adolescents (ages 1 to 17):

• •for up to 12 weeks to treat GERD and erosive esophagitis in children 1 to 11 years old.
• •for up to 8 weeks to treat GERD and erosive esophagitis in adolescents 12 to 17 years old.

PREVACID is not effective for symptoms of GERD in children under the age of 1 year.

Who should not take PREVACID?

• •Do not take PREVACID if you are allergic to lansoprazole or any of the other ingredients in PREVACID. See the end of this Medication Guide for a complete list of ingredients in PREVACID.

What should I tell my doctor before taking PREVACID?

Before you take PREVACID, tell your doctor if you:

• •have been told that you have low magnesium levels in your blood.
• •have liver problems
• •have phenylketonuria. PREVACID SoluTab contains aspartame.
• •have any other medical conditions
• •are pregnant or plan to become pregnant. It is not known if PREVACID will harm your unborn baby.
• •are breastfeeding or plan to breastfeed. It is not known if PREVACID passes into your breast milk. You and your doctor should decide if you will take PREVACID or breastfeed. You should not do both. Talk to your doctor about the best way to feed your baby if you take PREVACID.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

PREVACID may affect how other medicines work, and other medicines may affect how PREVACID works.

Especially tell your doctor if you take:

• •atazanavir (Reyataz)
• •digoxin (Lanoxin)
• •a product that contains iron
• •ketoconazole (Nizoral)
• •warfarin (Coumadin, Jantoven)
• •tacrolimus (Prograf)
• •theophylline (Theo-24, Elixophyllin, Theochron, Theolair)
• •an antibiotic that contains ampicillin or clarithromycin
• •methotrexate

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take PREVACID?

• •Take PREVACID exactly as prescribed by your doctor.
• •Do not change your dose or stop taking PREVACID without talking to your doctor.
• •You should take PREVACID before eating.
• • PREVACID Delayed-Release Capsules:
  • ∘You should swallow PREVACID Delayed-Release Capsules whole.
  • ∘ Do not crush or chew PREVACID Delayed-Release Capsules.
  • ∘If you have trouble swallowing a whole capsule, you can open the capsule and take the contents with certain foods or juices. See the "Instructions for Use" at the end of this Medication Guide for instructions on how to take PREVACID capsules with certain foods and juices.
  • ∘See the "Instructions for Use" at the end of this Medication Guide for instructions on how to mix and give PREVACID capsules through a nasogastric tube.
• • PREVACID SoluTab :
  • ∘is a tablet that melts in your mouth with or without water.
  • ∘ Do not break, cut or chew the tablets.
  • ∘See the "Instructions for Use" at the end of this Medication Guide for instructions on how to mix and give PREVACID SoluTab tablets through a syringe and nasogastric tube.
• •If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Just take the next dose at your regular time. Do not take 2 doses at the same time.
• •If you take too much PREVACID, call your doctor right away.

What are the possible side effects of PREVACID?

PREVACID can cause serious side effects, including:

• • See “What is the most important information that I should know about PREVACID?”
• • Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in some people who take a proton pump inhibitor medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment. You may or may not have symptoms of low magnesium.

Tell your doctor right away if you develop any of these symptoms:

• •seizures
• •dizziness
• •abnormal or fast heartbeat
• •jitteriness
• •jerking movements or shaking (tremors)
• •muscle weakness
• •spasms of the hands and feet
• •cramps or muscle aches
• •spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking PREVACID, or during treatment; if you will be taking PREVACID for a long period of time.

The most common side effects of PREVACID in adults and children include:

• •diarrhea
• •stomach pain
• •nausea
• •constipation
• •headache

Other side effects:

• • Serious allergic reactions. Tell your doctor if you get any of the following symptoms with PREVACID.
  • ∘rash
  • ∘face swelling
  • ∘throat tightness
  • ∘difficulty breathing

Your doctor may stop PREVACID if these symptoms happen.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of PREVACID. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088.

How should I store PREVACID?

• •Store PREVACID at room temperature between 68°F to 77°F (20°C to 25°C).

Keep PREVACID and all medicines out of the reach of children.

General information about PREVACID

Medicines are sometimes prescribed for conditions other than those listed in a Medication Guide. Do not use PREVACID for conditions for which it was not prescribed. Do not give PREVACID to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about PREVACID. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about PREVACID that is written for healthcare professionals.

For more information go to www.PREVACID.com or call 1-877-825-3327.

What are the ingredients in PREVACID?

Active ingredient: lansoprazole.

Inactive ingredients in PREVACID Delayed-Release Capsules:

Sugar sphere, sucrose, methacrylic acid copolymer, low substituted hydroxypropyl cellulose, starch, magnesium carbonate, talc, polyethylene glycol, titanium dioxide, polysorbate 80, hydroxypropyl cellulose, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, and FD&C Red No. 40.

In addition PREVACID 15 mg Capsule only: FD&C Green No. 3.

Inactive ingredients in PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets:

Mannitol, methacrylic acid, hydroxypropyl cellulose, lactose monohydrate-microcrystalline cellulose sphere, triethyl citrate, crospovidone, polyacrylate, magnesium carbonate, aspartame, glyceryl monostearate, hypromellose, magnesium stearate, citric acid, titanium dioxide, talc, artificial strawberry flavor, polyethylene glycol, polysorbate 80 and ferric oxide.

PREVACID SoluTab contains phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg Tablet.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: September 2012

PRV012 R43

Instructions for Use

PREVACID ( prev -a- sid )
( lansoprazole )
Delayed-Release Capsules
and
PREVACID SoluTab ( prev -a- sid sol-u-tab)
( lansoprazole )
Delayed-Release Orally Disintegrating Tablets

PREVACID Delayed-Release Capsules

• •Swallow PREVACID Delayed-Release Capsules whole. Do not crush or chew them.
• •You should take PREVACID before eating.
• • PREVACID Delayed-Release Capsule with certain food :
  You can only use applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
•  1 Open the capsule.
•  2 Sprinkle the granules on 1 tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
•  3 Swallow right away.

• • PREVACID Delayed-Release Capsule with certain juices :
  You can only use apple juice, orange juice or tomato juice.
•  1 Open the capsule.
•  2 Sprinkle the granules into 60 mL (about ¼ cup) of either apple juice, orange juice or tomato juice.
•  3 Stir.
•  4 Swallow right away.
•  5 To make sure that the entire dose is taken, rinse the glass with 1/2 cup or more of juice to get out any leftover granules. Swallow the juice right away.

• • PREVACID Delayed-Release Capsules through a nasogastric tube (NG tube) 16 French or larger, as prescribed by your doctor :
  You can only use apple juice.
•  1 Open the capsule and empty the granules into a syringe.
•  2 Do not break or crush the granules.
•  3 Mix with 40 mL of apple juice. Do not use other liquids.
•  4 Attach the syringe to the NG tube and give the medicine in the syringe through the NG tube into the stomach.
•  5 After giving the granules, flush the NG tube with more apple juice to clear the tube.

PREVACID should not be used in foods or liquids not listed above.

• • PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets
•  1 Do not chew, crush, cut or break tablets.
•  2 Put the tablet on the tongue and let it dissolve, with or without water.
•  3 Swallow after the tablet dissolves.
•  4 The tablet usually dissolves in less than 1 minute.

• • PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets with an oral syringe:
•  1 Put a 15 mg tablet in an oral syringe and add 4 mL of water, or put a 30 mg tablet in an oral syringe and add 10 mL of water.
•  2 Shake the syringe gently to dissolve the tablet quickly.
•  3 After the tablet has dissolved, give the mixture within 15 minutes.
•  4 To make sure that the entire dose is taken, refill the syringe with about 2 mL (5 mL for the 30 mg tablet) of water, shake gently, and give the water in the syringe.

• • PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets through a nasogastric tube (NG tube) 8 French or larger, as prescribed by your doctor:
•  1 Put a 15 mg tablet in a syringe and add 4 mL of water, or put a 30 mg tablet in a syringe and add 10 mL of water.
•  2 Shake the syringe gently to dissolve the tablet quickly.
•  3 After the tablet has dissolved, give the mixture in the syringe through the NG tube into the stomach within 15 minutes.
•  4 Refill the syringe with about 5 mL of water, shake gently, and flush the NG tube.

How should I store PREVACID?

• •Store PREVACID at room temperature between 68°F to 77°F (20°C to 25°C).

Keep PREVACID and all medicines out of the reach of children.

This Instruction for Use has been approved by the U.S. Food and Drug Administration.

Distributed by:
Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015

Revised: September 2012

PREVACID is a trademark registered in the U.S. Patent and Trademark Office and SoluTab is a trademark of Takeda Pharmaceuticals U.S.A., Inc. and used under license by Takeda Pharmaceuticals America, Inc.

All other trademark names are the property of their respective owners.

©1995 - 2012 Takeda Pharmaceuticals America, Inc.

PRV012 R43

PRINCIPAL DISPLAY PANEL - 15 mg Capsule Bottle Label

NDC 64764-541-19
1000 Capsules

PREVACID ^®
LANSOPRAZOLE
DELAYED-RELEASE CAPSULES

15 mg

Rx only

Dispense the accompanying Medication Guide to each patient

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