CATEGORIES: Ulcer, duodenal; Esophagitis, erosive; Gastroesophageal Reflux Disease; Ulcer, gastric; Zollinger-Ellison syndrome; Ulcer, NSAID-associated, prophylaxis; Pregnancy Category B; FDA Approved May 1995
Drug Classes: Gastrointestinals; Proton pump inhibitors
BRAND NAMES: Prevacid; Prevacid SoluTab
FOREIGN BRAND AVAILABILITY:
Agopton (Austria, Germany, Switzerland);
Betalans (Indonesia);
Compraz (Indonesia);
Digest (Indonesia);
Ilsatec (Mexico);
Keval (Mexico);
Lancid (Korea);
Lancopen (Colombia);
Lanpraz (Colombia);
Lanprol (Israel);
Lanproton (Colombia);
Lansazol (Israel);
Lansopep (Colombia);
Lanston (Korea);
Lanvell (Indonesia);
Lanximed (Colombia);
Lanz (Philippines);
Lanzol-30 (India);
Lanzopral (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama, Peru);
Lanzor (France, Germany, South Africa);
Lapraz (Indonesia);
Laproton (Indonesia);
Laz (Indonesia);
Lopral (Colombia, Peru);
Neutron (Colombia);
Ogast (France);
Ogastro (Colombia, Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Peru);
Prolanz (Indonesia);
Prosogan (Indonesia);
Suprecid (Philippines);
Takepron (South Africa, China, Hong Kong, Japan, Taiwan);
Ulpax (Mexico);
Zoton (England, Ireland, Israel)
COST OF THERAPY:
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The active ingredient in Prevacid delayed-release capsules, delayed-release oral suspension, and delayed-release orally disintegrating tablets is 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.
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 2 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 hours 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.
Prevacid Delayed-Release Capsules
The delayed-release capsules contain the active ingredient, lansoprazole, in the form of enteric-coated granules and are available in two dosage strengths: 15 and 30 mg of lansoprazole per capsule. Each delayed-release capsule contains enteric-coated granules consisting of lansoprazole, 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. 3 (Prevacid 15-mg capsules only), and FD&C red no. 40.
Pravacid for Delayed-Release Orally Disintegrating Tablets
Prevacid for delayed-release orally disintegrating tablets contain the active ingredient, lansoprazole in the form of enteric-coated microgranules. The tablets are available in 15 and 30 mg dosage strengths. Each tablet contains lansoprazole and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, magnesium carbonate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, titanium dioxide, talc, mannitol, methacrylic acid, polyacrylate, polyethylene glycol, glyceryl monostearate, polysorbate 80, triethyl citrate, ferric oxide, citric acid, crospovidone, aspartame,* strawberry flavor and magnesium stearate.
*Phenylketonurics: Contains phenylalanine 2.5 mg/15-mg tablet and 5.1 mg/30-mg tablet.
Prevacid for Delayed-Release Oral Suspension
Prevacid for delayed-release oral suspension is composed of the active ingredient, lansoprazole, in the form of enteric-coated granules and also contains inactive granules. The packets contain lansoprazole granules which are identical to those contained in Prevacid delayed-release capsules and are available in 15 and 30 mg strengths. Inactive granules are composed of the following ingredients: 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.
Pharmacokinetics and Metabolism
Prevacid delayed-release capsules, delayed-release orally disintegrating tablets and 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. Peak plasma concentrations of lansoprazole (Cmax) and the area under the plasma concentration curve (AUC) of lansoprazole are approximately proportional in doses from 15-60 mg after single-oral administration. Lansoprazole does not accumulate and its pharmacokinetics are unaltered by multiple dosing.
Absorption
The absorption of lansoprazole is rapid, with mean Cmax occurring approximately 1.7 hours after oral dosing, and relatively complete with absolute bioavailability over 80%. In healthy subjects, the mean (±SD) plasma half-life was 1.5 (±1.0) hours. Both Cmax and AUC are diminished by about 50-70% if the drug is given 30 minutes after food as opposed to the fasting condition. There is no significant food effect if the drug is given before meals.
Distribution
Lansoprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 0.05-5.0 μg/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 2 active species which inhibit acid secretion by (H+,K+)-ATPase within the parietal cell canaliculus, but are not present in the systemic circulation. The plasma elimination half-life of lansoprazole does not reflect its duration of suppression of gastric acid secretion. Thus, the plasma elimination half-life is less than 2 hours, while the acid inhibitory effect lasts more than 24 hours.
Elimination
Following single-dose oral administration of lansoprazole, 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 metabolites of lansoprazole.
Special Populations
Geriatric
The clearance of lansoprazole is decreased in the elderly, with elimination half-life increased approximately 50-100%. Because the mean half-life in the elderly remains between 1.9-2.9 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.
Pediatric
The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged 1-11 years, with lansoprazole doses of 15 mg qd for subjects weighing ≤30 kg and 30 mg qd for subjects weighing >30 kg. Lansoprazole pharmacokinetics in these pediatric patients were similar to that observed in healthy adult subjects. The mean Cmax and AUC values were similar between the 2-dose groups and were not affected by weight or age within each weight-adjusted dose group used in this study.
Gender
In a study comparing 12 male and 6 female human subjects, no gender differences were found in pharmacokinetics and intragastric pH results. (Also see PRECAUTIONS, Use in Women.)
Renal Insufficiency
In patients with severe renal insufficiency, plasma protein binding decreased by 1.0-1.5% after administration of 60 mg of lansoprazole. Patients with renal insufficiency had a shortened elimination half-life and decreased total AUC (free and bound). AUC for free lansoprazole in plasma, however, was not related to the degree of renal impairment, and Cmax and Tmax were not different from subjects with healthy kidneys. No dosage adjustment is necessary in patients with renal insufficiency.
Hepatic Insufficiency
In patients with various degrees of chronic hepatic disease, the mean plasma half-life of the drug was prolonged from 1.5 hours to 3.2-7.2 hours. An increase in mean AUC of up to 500% was observed at steady-state in hepatically-impaired patients compared to healthy subjects. Dose reduction in patients with severe hepatic disease should be considered.
Race
The pooled mean pharmacokinetic parameters of lansoprazole from twelve US Phase 1 studies (n=513) were compared to the mean pharmacokinetic parameters from two Asian studies (n=20). The mean AUCs of lansoprazole in Asian subjects were approximately twice those seen in pooled US data; however, the inter-individual variability was high. The Cmax values were comparable.
Pharmacodynamics
Mechanism of Action
Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but 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.
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 >3 and >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.
In a crossover study that included lansoprazole 15 and 30 mg for 5 days, the following effects on intragastric pH were noted (see TABLE 1).
After the initial dose in this study, increased gastric pH was seen within 1-2 hours with lansoprazole 30 mg and 2-3 hours with lansoprazole 15 mg. After multiple daily dosing, increased gastric pH was seen within the first hour postdosing with lansoprazole 30 mg and within 1-2 hours postdosing with lansoprazole 15 mg.
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 lansoprazole given qd, bid, and tid.
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| * (p <0.05) versus lansoprazole 30 mg qd. | |||||||||||||||||||||
| † (p <0.05) versus lansoprazole 30 mg qd, 15 mg bid, and 30 mg bid. | |||||||||||||||||||||
The inhibition of gastric acid secretion as measured by intragastric pH returns gradually to normal over 2-4 days after multiple doses. There is 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 7 days/week, marked hypergastrinemia was observed followed by ECL cell proliferation and formation of carcinoid tumors, especially in female rats. (See PRECAUTIONS, Carcinogenesis, Mutagenesis, and Impairment of Fertility.)
Gastric biopsy specimens from the body of the stomach from approximately 150 patients treated continuously with lansoprazole for at least 1 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.
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 50-100% from baseline but remained within normal range after treatment with lansoprazole given orally in doses of 15-60 mg. These elevations reached a plateau within 2 months of therapy and returned to pretreatment levels within 4 weeks after discontinuation of therapy.
Endocrine Effects
Human studies for up to 1 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 15-60 mg for up to 1 year had no clinically significant effect on sexual function. In addition, lansoprazole in oral doses of 15-60 mg for 2-8 weeks had no clinically significant effect on thyroid function.
In 24-month carcinogenicity studies in Sprague-Dawley rats with daily dosages up to 150 mg/kg, proliferative changes in the Leydig cells of the testes, including benign neoplasm, were increased compared to control rates.
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. No visual toxicity was observed among 56 patients who had extensive baseline eye evaluations, were treated with up to 180 mg/day of lansoprazole and were observed for up to 58 months. Other rat-specific findings after lifetime exposure included focal pancreatic atrophy, diffuse lymphoid hyperplasia in the thymus, and spontaneous retinal atrophy.
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 INDICATIONS AND USAGE.
Helicobacter — Helicobacter pylori
Pretreatment Resistance
Clarithromycin pretreatment resistance (≥2.0 μg/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 μg/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 (21) of 957 patients (2.2%) by E-test and 2 of 100 patients (2.0%) by agar dilution had amoxicillin pretreatment MICs of >0.25 μg/ml. One patient on the 14-day triple therapy regimen had an unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of >256 μg/ml by E-test and the patient was eradicated of H. pylori.
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| * Includes only patients with pretreatment clarithromycin susceptibility test results. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| † Susceptible (S) MIC ≤0.25 μg/ml, Intermediate (I) MIC 0.5-1.0 μg/ml, Resistant (R) MIC ≥2 μg/ml. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 μg/ml) were eradicated of H. pylori. Of those with pretreatment amoxicillin MICs of >0.25 μg/ml, 3 of 6 had the H. pylori eradicated. A total of 30% (21/70) of the patients failed lansoprazole 30 mg tid/amoxicillin 1 g tid 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 (9) 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
The reference methodology for susceptibility testing of H. pylori is agar dilution MICs. 1 One to three microliters (1-3 μl) of an inoculum equivalent to a no. 2 McFarland standard (1 × 107 to 1 × 108 CFU/ml for H. pylori) are inoculated directly onto freshly prepared antimicrobial-containing Mueller-Hinton agar plates with 5% aged defibrinated sheep blood (≥2 weeks old). The agar dilution plates are incubated at 35°C in a microaerobic environment produced by a gas generating system suitable for campylobacters. After 3 days of incubation, the MICs are recorded as the lowest concentration of antimicrobial agent required to inhibit growth of the organism. The clarithromycin and amoxicillin MIC values should be interpreted according to the criteria in TABLE 4.
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| * These are tentative breakpoints for the agar dilution methodology and they should not be used to interpret results obtained using alternative methods. | ||||||||||||||||
| † There were not enough organisms with MICs >0.25 μg/ml to determine a resistance breakpoint. | ||||||||||||||||
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard clarithromycin and amoxicillin powders should provide the MIC values in TABLE 5.
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| * These are quality control ranges for the agar dilution methodology and they should not be used to control test results obtained using alternative methods. | ||||||||||||
Duodenal Ulcer
In a US multicenter, double-blind, placebo-controlled, dose-response (15, 30, and 60 mg of lansoprazole once daily) study of 284 patients with endoscopically documented duodenal ulcer, the percentage of patients healed after 2 and 4 weeks was significantly higher with all doses of lansoprazole than with placebo. There was no evidence of a greater or earlier response with the two higher doses compared with lansoprazole 15 mg. Based on this study and the second study described in TABLE 6, the recommended dose of lansoprazole in duodenal ulcer is 15 mg/day.
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| * (p ≤0.001) versus placebo. | ||||||||||||||||||||||||||||||
Lansoprazole 15 mg was significantly more effective than placebo in relieving day and nighttime abdominal pain and in decreasing the amount of antacid taken per day.
In a second US multicenter study, also double-blind, placebo-controlled, dose-comparison (15 and 30 mg of lansoprazole once daily), and including a comparison with ranitidine, in 280 patients with endoscopically documented duodenal ulcer, the percentage of patients healed after 4 weeks was significantly higher with both doses of lansoprazole than with placebo. There was no evidence of a greater or earlier response with the higher dose of lansoprazole. Although the 15-mg dose of lansoprazole was superior to ranitidine at 4 weeks, the lack of significant difference at 2 weeks and the absence of a difference between 30 mg of lansoprazole and ranitidine leaves the comparative effectiveness of the two agents undetermined.
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| * (p ≤0.05) versus placebo and ranitidine. | ||||||||||||||||||||||||||||||
| † (p ≤0.05) versus placebo. | ||||||||||||||||||||||||||||||
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
Randomized, double-blind clinical studies performed in the US in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within 1 year) evaluated the efficacy of lansoprazole 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 US in patients with H. pylori and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within 1 year) compared the efficacy of lansoprazole triple therapy for 10 and 14 days. This study established that the 10-day triple therapy was equivalent to the 14-day triple therapy in eradicating H. pylori.
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| * Based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H. pylori infection at baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest, histology and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the evaluable analysis as failures of therapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| † Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within 1 year). All dropouts were included as failures of therapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ‡ (p <0.05) versus lansoprazole/amoxicillin and lansoprazole/clarithromycin dual therapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| § (p <0.05) versus clarithromycin/amoxicillin dual therapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ¤ The 95% confidence interval for the difference in eradication rates, 10-day minus 14-day is (-10.5, 8.1) in the evaluable analysis and (-9.7, 9.1) in the intent-to-treat analysis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| * Based on evaluable patients with confirmed duodenal ulcer (active or within 1 year) and H. pylori infection at baseline defined as at least 2 of 3 positive endoscopic tests from CLOtest, histology and/or culture. Patients were included in the analysis if they completed the study. Additionally, if patients dropped out of the study due to an adverse event related to the study drug, they were included in the analysis as failures of therapy. | |||||||||||||||||||||||||||
| † Patients were included in the analysis if they had documented H. pylori infection at baseline as defined above and had a confirmed duodenal ulcer (active or within 1 year). All dropouts were included as failures of therapy. | |||||||||||||||||||||||||||
| ‡ (p <0.05) versus lansoprazole alone. | |||||||||||||||||||||||||||
| § (p <0.05) versus lansoprazole alone or amoxicillin alone. | |||||||||||||||||||||||||||
Long-Term Maintenance Treatment of Duodenal Ulcers
Lansoprazole has been shown to prevent the recurrence of duodenal ulcers. Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed duodenal ulcers. Patients remained healed significantly longer and the number of recurrences of duodenal ulcers was significantly less in patients treated with lansoprazole than in patients treated with placebo over a 12-month period.
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| % = Life Table Estimate. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| * (p ≤0.001) versus placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
In trial no. 2, no significant difference was noted between lansoprazole 15 and 30 mg in maintaining remission.
Gastric Ulcer
In a US multicenter, double-blind, placebo-controlled study of 253 patients with endoscopically documented gastric ulcer, the percentage of patients healed at 4 and 8 weeks was significantly higher with lansoprazole 15 and 30 mg once a day than with placebo.
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| * (p ≤0.05) versus placebo. | ||||||||||||||||||||||||||||||
Patients treated with any lansoprazole dose reported significantly less day and night abdominal pain along with fewer days of antacid use and fewer antacid tablets used per day than the placebo group.
Independent substantiation of the effectiveness of lansoprazole 30 mg was provided by a meta-analysis of published and unpublished data.
Healing of NSAID-Associated Gastric Ulcer
In two US 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 lansoprazole than with the active control. A total of 711 patients were enrolled in the study, and 701 patients were treated. Patients ranged in age from 18-88 years (median age 59 years), with 67% female patients and 33% male patients. Race was distributed as follows: 87% Caucasian, 8% black, 5% other. There was no statistically significant difference between lansoprazole 30 mg qd and the active control on symptom relief (i.e., abdominal pain).
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| * Actual observed ulcer(s) healed at time points ±2 days. | ||||||||||||||||||||||||||||||||
| † Dose for healing of gastric ulcer. | ||||||||||||||||||||||||||||||||
| ‡ (p ≤0.05) versus the active control. | ||||||||||||||||||||||||||||||||
Risk Reduction of NSAID-Associated Gastric Ulcer
In one large US, 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 lansoprazole than placebo. A total of 537 patients were enrolled in the study, and 535 patients were treated. Patients ranged in age from 23-89 years (median age 60 years), with 65% female patients and 35% male patients. Race was distributed as follows: 90% Caucasian, 6% black, 4% other. The 30-mg dose of lansoprazole demonstrated no additional benefit in risk reduction of the NSAID-associated gastric ulcer than the 15-mg dose.
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| * % = Life Table Estimate. | |||||||||||||||||||||||||||||||||||
| (p <0.001) Lansoprazole 15 mg qd versus placebo; lansoprazole 30 mg qd versus placebo; and misoprostol 200 μg qid versus placebo. | |||||||||||||||||||||||||||||||||||
| (p <0.05) Misoprostol 200 μg qid versus lansoprazole 15 mg qd; and misoprostol 200 μg qid versus lansoprazole 30 mg qd. | |||||||||||||||||||||||||||||||||||
Gastroesophageal Reflux Disease (GERD)
Symptomatic GERD
In a US 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 were as shown in TABLE 14.
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| * (p <0.01) versus placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
In two US, 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 (bid) 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.
Erosive Esophagitis
In a US 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 were as shown in TABLE 15.
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| * (p ≤0.001) versus placebo. | |||||||||||||||||||||||||||||||||||
| † (p ≤0.05) versus lansoprazole 15 mg and placebo. | |||||||||||||||||||||||||||||||||||
In this study, all lansoprazole groups reported significantly greater relief of heartburn and less day and night abdominal pain along with fewer days of antacid use and fewer antacid tablets taken per day than the placebo group.
Although all doses were effective, the earlier healing in the higher two doses suggests 30 mg qd as the recommended dose.
Lansoprazole was also compared in a US multicenter, double-blind study to a low dose of ranitidine in 242 patients with erosive reflux esophagitis. Lansoprazole at a dose of 30 mg was significantly more effective than ranitidine 150 mg bid as shown in TABLE 16.
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| * (p ≤0.001) versus ranitidine. | |||||||||||||||||||||
In addition, patients treated with lansoprazole reported less day and nighttime heartburn and took less antacid tablets for fewer days than patients taking ranitidine 150 mg bid.
Although this study demonstrates effectiveness of lansoprazole in healing erosive esophagitis, it does not represent an adequate comparison with ranitidine because the recommended ranitidine dose for esophagitis is 150 mg qid, twice the dose used in this study.
In the two trials described and in several smaller studies involving patients with moderate to severe erosive esophagitis, lansoprazole produced healing rates similar to those shown above.
In a US multicenter, double-blind, active-controlled study, 30 mg of lansoprazole was compared with ranitidine 150 mg bid in 151 patients with erosive reflux esophagitis that was poorly responsive to a minimum of 12 weeks of treatment with at least one H2-receptor antagonist given at the dose indicated for symptom relief or greater, namely, cimetidine 800 mg/day, ranitidine 300 mg/day, famotidine 40 mg/day or nizatidine 300 mg/day. Lansoprazole 30 mg was more effective than ranitidine 150 mg bid in healing reflux esophagitis, and the percentage of patients with healing is shown in TABLE 17. This study does not constitute a comparison of the effectiveness of histamine H2-receptor antagonists with lansoprazole, as all patients had demonstrated unresponsiveness to the histamine H2-receptor antagonist mode of treatment. It does indicate, however, that lansoprazole may be useful in patients failing on a histamine H2-receptor antagonist.
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| * (p ≤0.001) versus ranitidine. | |||||||||||||||
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 lansoprazole than in patients treated with placebo over a 12-month period.
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| % = Life Table Estimate. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| * (p ≤0.001) versus placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Regardless of initial grade of erosive esophagitis, lansoprazole 15 and 30 mg were similar in maintaining remission.
In a US, randomized, double-blind, study, lansoprazole 15 mg qd (n=100) was compared with ranitidine 150 mg bid (n=106), at the recommended dosage, in patients with endoscopically-proven healed erosive esophagitis over a 12-month period. Treatment with lansoprazole resulted in patients remaining healed (Grade 0 lesions) of erosive esophagitis for significantly longer periods of time than those treated with ranitidine (p <0.001). In addition, lansoprazole was significantly more effective than ranitidine in providing complete relief of both daytime and nighttime heartburn. Patients treated with lansoprazole remained asymptomatic for a significantly longer period of time than patients treated with ranitidine.
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
In open studies of 57 patients with pathological hypersecretory conditions, such as Zollinger-Ellison (ZE) syndrome with or without multiple endocrine adenomas, lansoprazole significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia and pain. Doses ranging from 15 mg every other day to 180 mg/day maintained basal acid secretion below 10 mEq/h in patients without prior gastric surgery and below 5 mEq/h 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.) Lansoprazole was well-tolerated at these high dose levels for prolonged periods (greater than 4 years in some patients). In most ZE patients, serum gastrin levels were not modified by lansoprazole. However, in some patients, serum gastrin increased to levels greater than those present prior to initiation of lansoprazole therapy.
Lansoprazole delayed-release capsules, delayed-release orally disintegrating tablets and delayed-release oral suspension are indicated for:
Short-Term Treatment of Active Duodenal Ulcer
Lansoprazole is indicated for short-term treatment (up to 4 weeks) for healing and symptom relief of active duodenal ulcer.
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence
Triple Therapy: Lansoprazole/Amoxicillin/Clarithromycin
Lansoprazole in combination with amoxicillin plus clarithromycin as triple therapy is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. (See CLINICAL STUDIES and DOSAGE AND ADMINISTRATION.)
Dual Therapy: Lansoprazole/Amoxicillin
Lansoprazole in combination with amoxicillin as dual therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. (See the clarithromycin package insert, Microbiology.) Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. (See CLINICAL STUDIES and DOSAGE AND ADMINISTRATION.)
Maintenance of Healed Duodenal Ulcers
Lansoprazole is indicated to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months.
Short-Term Treatment of Active Benign Gastric Ulcer
Lansoprazole is indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of active benign gastric ulcer.
Healing of NSAID-Associated Gastric Ulcer
Lansoprazole is indicated for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled studies did not extend beyond 8 weeks.
Risk Reduction of NSAID-Associated Gastric Ulcer
Lansoprazole is indicated for reducing the risk of NSAID-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an NSAID. Controlled studies did not extend beyond 12 weeks.
Gastroesophageal Reflux Disease (GERD)
Short-Term Treatment of Symptomatic GERD
Lansoprazole is indicated for the treatment of heartburn and other symptoms associated with GERD.
Short-Term Treatment of Erosive Esophagitis
Lansoprazole is indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of all grades of erosive esophagitis.
For patients who do not heal with lansoprazole for 8 weeks (5-10%), it may be helpful to give an additional 8 weeks of treatment.
If there is a recurrence of erosive esophagitis an additional 8-week course of lansoprazole may be considered.
Maintenance of Healing of Erosive Esophagitis
Lansoprazole is indicated to maintain healing of erosive esophagitis. Controlled studies did not extend beyond 12 months.
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
Lansoprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.
Prevacid is contraindicated in patients with known 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 with cisapride, pimozide, astemizole, or terfenadine is contraindicated. There have been postmarketing reports of drug interactions when clarithromycin and/or erythromycin are coadministered 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.
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 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.
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, IV STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.
General
Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.
Information for the Patient
Lansoprazole is available as a capsule, orally disintegrating tablet and oral suspension, and is available in 15- 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. Lansoprazole should be taken before eating. Lansoprazole products SHOULD NOT BE CRUSHED OR CHEWED.
Phenylketonurics: Contains phenylalanine 2.5-mg/15-mg tablet and 5.1-mg/30-mg tablet.
Administration Options
Lansoprazole Delayed-Release Capsules
Lansoprazole delayed-release capsules should be swallowed whole.
Alternatively, for patients who have difficulty swallowing capsules, lansoprazole delayed-release capsules can be opened and administered as follows:
Lansoprazole delayed-release capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows:
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
Lansoprazole Delayed-Release Orally Disintegrating Tablets
Lansoprazole delayed-release orally disintegrating tablets are not designed to be swallowed intact or chewed. The tablet typically disintegrates in less than 1 minute.
Lansoprazole for Delayed-Release Oral Suspension
Lansoprazole for delayed-release oral suspension should be administered as follows:
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated orally with doses of 5-150 mg/kg/day, about 1-40 times the exposure on a body surface (mg/m2) basis, of a 50-kg person of average height (1.46 m2 body surface area) 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 15-150 mg/kg/day (4-40 times the recommended human dose based on body surface area) exceeded the low background incidence (range = 1.4-10%) for this strain of rat. Testicular interstitial cell adenoma also occurred in 1 of 30 rats treated with 50 mg/kg/day (13 times the recommended human dose based on body surface area) in a 1-year toxicity study.
In a 24-month carcinogenicity study, CD-1 mice were treated orally with doses of 15-600 mg/kg/day, 2-80 times the recommended human dose based on body surface area. 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 (40-80 times the recommended human dose based on body surface area) and female mice treated with 150-600 mg/kg/day (20-80 times the recommended human dose based on body surface area) 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 75-600 mg/kg/day (10-80 times the recommended human dose based on body surface area).
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 body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.
Pregnancy, Teratogenic Effects
Pregnancy Category B — Lansoprazole
Teratology studies have been performed in pregnant rats at oral doses up to 150 mg/kg/day (40 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to lansoprazole.
There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category C — Clarithromycin
See WARNINGS and full prescribing information for clarithromycin before using in pregnant women.
Nursing Mothers
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 the drug, taking into account the importance of the drug to the mother.
Pediatric Use
The safety and effectiveness of lansoprazole have been established in the age group 1-11 years for short-term treatment of symptomatic GERD and erosive esophagitis. Safety and effectiveness have not been established in patients <1 year or 12-17 years of age.
Use of lansoprazole in the age group 1-11 years is supported by evidence from adequate and well controlled studies of lansoprazole in adults with additional clinical, pharmacokinetic, pharmacodynamic, and safety studies performed in pediatric patients.
In an uncontrolled, open-label, US multicenter study, 66 pediatric patients (1-11 years of age) with GERD were assigned, based on body weight, to receive an initial dose of either lansoprazole 15 mg qd if ≤30 kg or lansoprazole 30 mg qd if >30 kg administered for 8-12 weeks. The lansoprazole dose was increased (up to 30 mg bid) in 24 of 66 pediatric patients after 2 or more weeks of treatment if they remained symptomatic. At baseline 85% of patients had mild to moderate overall GERD symptoms (assessed by investigator interview), 58% had nonerosive GERD and 42% had erosive esophagitis (assessed by endoscopy).
After 8-12 weeks of lansoprazole treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of GERD symptoms.
Twenty-one (21) of 27 erosive esophagitis patients were healed at 8 weeks and 100% of patients were healed at 12 weeks by endoscopy.
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| * At Week 8 or Week 12. | |||||||||||||||||||||
| † Symptoms assessed by patients diary kept by caregiver. | |||||||||||||||||||||
| ‡ No data were available for 4 pediatric patients. | |||||||||||||||||||||
In a study of 66 pediatric patients in the age group 1-11 years old after treatment with lansoprazole given orally in doses of 15 mg qd to 30 mg bid, increases in serum gastrin levels were similar to those observed in adult studies. Median fasting serum gastrin levels increased 89% from 51 pg/ml at baseline to 97 pg/ml [interquartile range (25th-75th percentile) of 71-130 pg/ml] at the final visit.
The pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged 1-11 years of age. Of the 66 patients with GERD 85% (56/66) took lansoprazole for 8 weeks and 15% (10/66) took it for 12 weeks.
The adverse event profile in these pediatric patients resembled that of adults taking lansoprazole. The most frequently reported (2 or more patients) treatment-related adverse events in patients 1-11 years of age (n=66) were constipation (5%) and headache (3%). There were no adverse events reported in this US clinical study that were not previously observed in adults.
Use in Women
Over 4000 women were treated with lansoprazole. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse events were also similar to those seen in males.
Use in Geriatric Patients
Ulcer healing rates in elderly patients are similar to those in a younger age group. The incidence rates of adverse events and laboratory test abnormalities are also similar to those seen in younger patients. For elderly patients, dosage and administration of lansoprazole need not be altered for a particular indication.
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.
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 g, 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 lansoprazole delayed-release capsules; this did not interfere with its effect.
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).
Clinical
Worldwide, over 10,000 patients have been treated with lansoprazole in Phase 2-3 clinical trials involving various dosages and durations of treatment. The adverse reaction profiles for lansoprazole delayed-release capsules and delayed-release oral suspension are similar. In general, lansoprazole 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 lansoprazole-treated patients and occurred at a greater rate in lansoprazole-treated patients than placebo-treated patients (see TABLE 20).
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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 lansoprazole 15 and 30 mg, but higher in the patients who received lansoprazole 60 mg (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 lansoprazole for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with lansoprazole was 5%, misoprostol 22%, and placebo 3%.
Additional adverse experiences occurring in <1% of patients or subjects in domestic trials are shown below. Refer to Postmarketing for adverse reactions occurring since the drug was marketed.
Postmarketing
On-Going Safety Surveillance
Additional adverse experiences have been reported since lansoprazole has been marketed. The majority of these cases are foreign-sourced and a relationship to lansoprazole 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 listed below by COSTART body system.
Combination Therapy With Amoxicillin and Clarithromycin
In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole 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 lansoprazole, amoxicillin, or clarithromycin.
Triple Therapy: Lansoprazole/Amoxicillin/Clarithromycin
The most frequently reported adverse events for patients who received triple therapy for 14 days were diarrhea (7%), headache (6%), and taste perversion (5%). There were no statistically significant differences in the frequency of reported adverse events between the 10- and 14-day triple therapy regimens. No treatment-emergent adverse events were observed at significantly higher rates with triple therapy than with any dual therapy regimen.
Dual Therapy: Lansoprazole/Amoxicillin
The most frequently reported adverse events for patients who received lansoprazole tid plus amoxicillin tid dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher rates with lansoprazole tid plus amoxicillin tid dual therapy than with lansoprazole alone.
For more information on adverse reactions with amoxicillin or clarithromycin, refer to their package inserts, ADVERSE REACTIONS sections.
Laboratory Values
The following changes in laboratory parameters for lansoprazole were reported as adverse events:
In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) placebo patients and 0.4% (11/2677) lansoprazole patients had enzyme elevations greater than 3 times the upper limit of normal range at the final treatment visit. None of these lansoprazole patients reported jaundice at any time during the study.
In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole 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.
Oral doses up to 5000 mg/kg in rats (approximately 1300 times the recommended human dose based on body surface area) and mice (about 675.7 times the recommended human dose based on body surface area) did not produce deaths or any clinical signs.
Lansoprazole is not removed from the circulation by hemodialysis. In one reported case of overdose, the patient consumed 600 mg of lansoprazole with no adverse reaction.
Lansoprazole is available as a capsule, orally disintegrating tablet and oral suspension, and is available in 15- 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. Lansoprazole should be taken before eating. Lansoprazole products SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with lansoprazole.
No dosage adjustment is necessary in patients with renal insufficiency or the elderly. For patients with severe liver disease, dosage adjustment should be considered.
Duodenal Ulcers
Short-Term Treatment:
Maintenance of Healed:
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence*
Triple Therapy:
Dual Therapy:
*Please refer to amoxicillin and clarithromycin full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally-impaired patients.
Benign Gastric Ulcer
Short-Term Treatment:
NSAID-Associated Gastric Ulcer
Healing:
Risk Reduction:
Gastroesophageal Reflux Disease (GERD)
Short-Term Treatment of Symptomatic GERD:
Short-Term Treatment of Erosive Esophagitis:
Pediatric (short-term treatment of symptomatic GERD, short-term treatment of erosive esophagitis) (1-11 years of age)
≤30 kg:
>30 kg:
Maintenance of Healing of Erosive Esophagitis
Pathological Hypersecretory Conditions Including Zollinger-Ellision Syndrome
Administration Options
Lansoprazole Delayed-Release Capsules
Oral Administration
Lansoprazole delayed-release capsules should be swallowed whole.
Alternatively, for patients who have difficulty swallowing capsules, lansoprazole delayed-release capsules can be opened and administered as follows:
Lansoprazole delayed-release capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows:
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
Nasogastric Tube Administration
For patients who have a nasogastric tube in place, lansoprazole delayed-release capsules can be adminsitered as follows:
Lansoprazole Delayed-Release Orally Disintegrating Tablets
Lansoprazole delayed-release orally disintegrating tablets are not designed to be swallowed intact or chewed. The tablet typically disintegrates in less than 1 minute.
Prevacid for Delayed-Release Oral Suspension
Prevacid for delayed-release oral suspension should be administered as follows:
References
1.Prevacid Delayed-Release Capsules
Storage: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
Prevacid Delayed-Release Oral Suspension
Prevacid for delayed-release oral suspension contains white to pale brownish lansoprazole granules and inactive pink granules in a unit dose packet containing 15 or 30 mg of lansoprazole.
Storage: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
Prevacid SoluTab Delayed-Release Orally Disintegrating Tablets
Storage: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).
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