PREVACID^®
(lansoprazole)
Delayed-Release Capsules
PREVACID^®
(lansoprazole)
For Delayed-Release Oral Suspension
PREVACID^® SoluTab^™
(lansoprazole)
Delayed-Release Orally Disintegrating Tablets

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:

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.

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 (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.

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.

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).

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).

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 4-6 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).

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).

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

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).

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.

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 10).

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).

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:

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.

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).

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.

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.

PREVACID Delayed-Release Capsules, PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets and PREVACID For Delayed-Release Oral Suspension are indicated for:

PREVACID is indicated for short-term treatment (for 4 weeks) for healing and symptom relief of active duodenal ulcer.

PREVACID is indicated to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months.

PREVACID is indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of active benign 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.

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.

PREVACID is indicated to maintain healing of erosive esophagitis. Controlled studies did not extend beyond 12 months.

PREVACID is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

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.

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.

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.

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.

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).

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 10%) for this strain of rat. In addition, in a one-year toxicity study, testicular interstitial cell adenoma occurred in 1 of 30 rats treated with 50 mg/kg/day of lansoprazole (13 times the recommended human dose based on BSA).

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).

Lansoprazole was not genotoxic in the Ames test, 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. It was positive in in vitro human lymphocyte chromosomal aberration assays.

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.

Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue lansoprazole, taking into account the importance of lansoprazole to the mother.

The safety and effectiveness of PREVACID have been established in pediatric patients 1 to 17 years of age for short-term treatment of symptomatic GERD and erosive esophagitis. Use of PREVACID in this population is supported by evidence from adequate and well-controlled studies of PREVACID in adults with additional clinical, pharmacokinetic, and pharmacodynamic studies performed in pediatric patients. The adverse events profile in pediatric patients is similar to that of adults. There were no adverse events reported in U.S. clinical studies that were not previously observed in adults. The safety and effectiveness of PREVACID in patients less than 1 year of age have not been established.

Over 4,000 women were treated with PREVACID. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse events in females were similar to those seen in males.

The incidence rates of PREVACID-associated adverse events and laboratory test abnormalities are similar to those seen in younger patients. For geriatric patients, dosage and administration of PREVACID need not be altered.

Worldwide, over 10,000 patients have been treated with PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. The adverse reaction profiles for PREVACID Delayed-Release Capsules and PREVACID for Delayed-Release Oral Suspension are similar. In general, PREVACID treatment has been well-tolerated in both short-term and long-term trials.

The following adverse events were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated patients than placebo-treated patients in Table 19.

Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhea was similar between patients who received placebo and patients who received 15 mg and 30 mg of PREVACID, but higher in the patients who received 60 mg of PREVACID (2.9%, 1.4%, 4.2%, and 7.4%, respectively).

The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.

In the risk reduction study of PREVACID for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with PREVACID, misoprostol, and placebo was 5%, 22%, and 3%, respectively.

Additional adverse experiences occurring in less than 1% of patients or subjects who received PREVACID in domestic trials are shown below:

Body as a Whole — abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain; Cardiovascular System - angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation; Digestive System — abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation, melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea, oral moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis; Endocrine System - diabetes mellitus, goiter, hypothyroidism; Hemic and Lymphatic System - anemia, hemolysis, lymphadenopathy; Metabolic and Nutritional Disorders - gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss; Musculoskeletal System - arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, synovitis; Nervous System — abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo; Respiratory System - asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor; Skin and Appendages - acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria; Special Senses — abnormal vision, blurred vision, conjunctivitis, deafness, dry eyes, ear disorder, eye pain, otitis media, parosmia, photophobia, retinal degeneration, taste loss, taste perversion, tinnitus, visual field defect; Urogenital System - abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary tract infection, urinary urgency, urination impaired, vaginitis.

Additional adverse experiences have been reported since PREVACID has been marketed. The majority of these cases are foreign-sourced and a relationship to PREVACID has not been established. Because these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are uled below by COSTART body system.

Body as a Whole - anaphylactic/anaphylactoid reactions; Digestive System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Musculoskeletal System - myositis; Skin and Appendages – severe dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal); Special Senses - speech disorder; Urogenital System – interstitial nephritis, urinary retention.

In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with PREVACID, amoxicillin, or clarithromycin.

The following changes in laboratory parameters in patients who received PREVACID were reported as adverse events:

Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, eosinophilia, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, and increased gastrin levels. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported.

In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who received placebo and PREVACID, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received PREVACID reported jaundice at any time during the study.

In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed.

For more information on laboratory value changes with amoxicillin or clarithromycin, refer to their package inserts, ADVERSE REACTIONS section.

PREVACID is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of PREVACID with no adverse reaction.

Oral PREVACID doses up to 5000 mg/kg in rats (approximately 1300 times the 30 mg human dose based on BSA) and in mice (about 675.7 times the 30 mg human dose based on BSA) did not produce deaths or any clinical signs.

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. In the clinical trials, antacids were used concomitantly with PREVACID.

Renal insufficiency patients and geriatric patients do not require dosage adjustment. However, dose adjustment should be considered in patients with severe liver disease.

• PREVACID Delayed-Release Capsules

PREVACID 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 spans swallowed immediately.

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

PREVACID Capsules - Nasogastric Tube 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.

• 2.PREVACID SoluTab Delayed-Release Orally Disintegrating Tablets

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 approximately 4 mL of water, or place a 30 mg tablet in oral syringe and draw up approximately 10 mL of water.
• Shake gently to allow for a quick dispersal.
• After the tablet has dispersed, administer the spans 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 spans.

PREVACID SoluTab — Nasogastric Tube Administration (≥ 8 French)

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.

• 3.PREVACID for Delayed-Release Oral Suspension

PREVACID for Delayed-Release Oral Suspension should be administered as follows:

• Open packet.
• To prepare a dose, empty the packet spans into a container containing 2 tablespoons of WATER. DO NOT USE OTHER LIQUIDS OR FOODS.
• Stir well, and drink immediately.
• If any material remains after drinking, add more water, stir, and drink immediately.
• This product should not be given through enteral administration tubes.

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

PREVACID for Delayed-Release Oral Suspension contains white to pale brownish lansoprazole granules and inactive pink granules in a unit dose packet. 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]