Lansoprazole Information
Lansoprazole () Dosage And Administration
Lansoprazole () delayed-release capsules are available as capsules in 15 mg and 30 mg strengths. Directions for use specific to the route and available methods of administration is presented below. Lansoprazole () delayed-release capsules should be taken before eating. Lansoprazole () delayed-release capsules SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with Lansoprazole () .
Lansoprazole () Contraindications
Lansoprazole () delayed-release capsules are contraindicated in patients with known severe hypersensitivity to any component of the formulation of Lansoprazole () . For information on contraindications for amoxicillin or clarithromycin, refer to their full prescribing information, CONTRAINDICATIONS sections.
Lansoprazole () Warnings And Precautions
Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines .
For information on warnings and precautions for amoxicillin or clarithromycin, refer to their full prescribing information, WARNINGS and PRECAUTIONS sections.
Lansoprazole () Adverse Reactions
Worldwide, over 10,000 patients have been treated with Lansoprazole () in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, Lansoprazole () treatment has been well tolerated in both short-term and long-term trials.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The following adverse reactions 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 in Table 1.
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 Lansoprazole () , but higher in the patients who received 60 mg of Lansoprazole () (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 () , misoprostol and placebo was 5%, 22% and 3%, respectively.
Another study for the same indication, where patients took either a COX-2 inhibitor or Lansoprazole () and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with Lansoprazole () included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia and renal impairment.
Additional adverse experiences occurring in less than 1% of patients or subjects who received Lansoprazole () in domestic trials are shown below:
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 reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed below by COSTART body system.
The following changes in laboratory parameters in patients who received Lansoprazole () were reported as adverse reactions:
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, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. 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% (11/2,677) patients, who received placebo and Lansoprazole () , respectively, had enzyme elevations greater than 3 times the upper limit of normal range at the final treatment visit. None of these patients who received Lansoprazole () 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 information on laboratory value changes with amoxicillin or clarithromycin, refer to their full prescribing information, ADVERSE REACTIONS sections.
Lansoprazole () Drug Interactions
Lansoprazole () causes long-lasting inhibition of gastric acid secretion. Lansoprazole () and other PPIs are likely to substantially decrease the systemic concentrations of the HIV protease inhibitor atazanavir, which is dependent upon the presence of gastric acid for absorption, and may result in a loss of therapeutic effect of atazanavir and the development of HIV resistance. Therefore, Lansoprazole () and other PPIs should not be coadministered with atazanavir.
It is theoretically possible that Lansoprazole () and other PPIs may interfere with the absorption of other drugs where gastric pH is an important determinant of oral bioavailability (e.g., ampicillin esters, digoxin, iron salts, ketoconazole).
In a study of healthy subjects, coadministration of single or multiple 60 mg doses of Lansoprazole () and warfarin did not affect the pharmacokinetics of warfarin nor prothrombin time . However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Concomitant administration of Lansoprazole () and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19.
A minor increase (10%) in the clearance of theophylline was observed following the administration of Lansoprazole () concomitantly with theophylline. Although the magnitude of the effect on theophylline clearance is small, individual patients may require additional titration of their theophylline dosage when Lansoprazole () is started or stopped to ensure clinically effective blood levels.
For information on drug interactions for amoxicillin or clarithromycin, refer to their full prescribing information, DRUG INTERACTIONS sections.
Lansoprazole () Overdosage
Lansoprazole () is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of Lansoprazole () with no adverse reaction. Oral Lansoprazole () doses up to 5000 mg/kg in rats [approximately 1,300 times the 30 mg human dose based on body surface area (BSA)] and in mice (about 675.7 times the 30 mg human dose based on BSA) did not produce deaths or any clinical signs.
Lansoprazole () Description
The active ingredient in Lansoprazole () delayed-release capsules, USP 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 molecular formula is CHFNOS with a molecular weight of 369.37. Lansoprazole () has the following structure:
Lansoprazole () , USP 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 hour at pH 5.0 and approximately 18 hours at pH 7.0.
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 pellets consisting of 15 mg or 30 mg of Lansoprazole () (active ingredient) and the following inactive ingredients: colloidal silicon dioxide, corn starch, hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, magnesium carbonate, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, sucrose, sugar spheres, talc and titanium dioxide. In addition, the 15 mg gelatin capsule contains FD&C Green No. 3 and FD&C Red No. 40; the 30 mg gelatin capsule contains FD&C Blue No. 1 and FD&C Red No 3; for both strengths the gelatin capsules contain gelatin and titanium dioxide.
The printing ink contains black iron oxide, propylene glycol, shellac and potassium hydroxide.
Lansoprazole () Clinical Pharmacology
It is theoretically possible that Lansoprazole () may interfere with the absorption of other drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).
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.
Lansoprazole () Nonclinical Toxicology
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/m) basis of a 50-kg person of average height [1.46 m body surface area (BSA)] given the recommended human dose of 30 mg/day. Lansoprazole () produced dose related gastric enterochromaffin-like (ECL) cell hyperplasia and ECL cell carcinoids in both male and female rats. It also increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes. In male rats, Lansoprazole () produced a dose related increase of testicular interstitial cell adenomas. The incidence of these adenomas in rats receiving doses of 15 to 150 mg/kg/day (4 to 40 times the recommended human dose based on BSA) exceeded the low background incidence (range = 1.4 to 10%) for this strain of rat.
In a 24-month carcinogenicity study, CD-1 mice were treated with oral Lansoprazole () doses of 15 to 600 mg/kg/day, 2 to 80 times the recommended human dose based on BSA. Lansoprazole () produced a dose related increased incidence of gastric ECL cell hyperplasia. It also produced an increased incidence of liver tumors (hepatocellular adenoma plus carcinoma). The tumor incidences in male mice treated with 300 and 600 mg/kg/day (40 to 80 times the recommended human dose based on BSA) and female mice treated with 150 to 600 mg/kg/day (20 to 80 times the recommended human dose based on BSA) exceeded the ranges of background incidences in historical controls for this strain of mice. Lansoprazole () treatment produced adenoma of rete testis in male mice receiving 75 to 600 mg/kg/day (10 to 80 times the recommended human dose based on BSA).
A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive.
Lansoprazole () was not genotoxic in the Ames test, the rat hepatocyte unscheduled DNA synthesis (UDS) test, the mouse micronucleus test, or the rat bone marrow cell chromosomal aberration test. It was positive in 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.
Reproductive Toxicology Studies
Reproduction studies have been performed in pregnant rats at oral Lansoprazole () doses up to 150 mg/kg/day [40 times the recommended human dose (30 mg/day) based on body surface area (BSA)] and pregnant rabbits at oral Lansoprazole () doses up to 30 mg/kg/day (16 times the recommended human dose based on BSA) and have revealed no evidence of impaired fertility or harm to the fetus due to Lansoprazole () .
Lansoprazole () Clinical Studies
In a U.S. multicenter, double-blind, placebo-controlled, dose-response (15 mg, 30 mg 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 below, the recommended dose of Lansoprazole () in duodenal ulcer is 15 mg per day (Table 9).
Lansoprazole () 15 mg was significantly more effective than placebo in relieving day and nighttime abdominal pain and in decreasing the amount of antacid taken per day.
In a second U.S. multicenter study, also double-blind, placebo-controlled, dose-comparison (15 mg 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 (Table 10).
Randomized, double-blind clinical studies performed in the U.S. in patients with and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) evaluated the efficacy of Lansoprazole () in combination with amoxicillin capsules and clarithromycin tablets as triple 14-day therapy or in combination with amoxicillin capsules as dual 14-day therapy for the eradication of Based on the results of these studies, the safety and efficacy of two different eradication regimens were established:
Triple therapy: Lansoprazole () 30 mg twice daily/amoxicillin 1 gram twice daily/clarithromycin 500 mg twice daily
Dual therapy: Lansoprazole () 30 mg 3 times daily/amoxicillin 1 gram 3 times daily
All treatments were for 14 days. eradication was defined as two negative tests (culture and histology) at 4 to 6 weeks following the end of treatment.
Triple therapy was shown to be more effective than all possible dual therapy combinations. Dual therapy was shown to be more effective than both monotherapies. Eradication of . 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 . and duodenal ulcer disease (defined as an active ulcer or history of an ulcer within one year) compared the efficacy of Lansoprazole () triple therapy for 10 and 14 days. This study established that the 10-day triple therapy was equivalent to the 14-day triple therapy in eradicating (Tables 11 and 12)
Lansoprazole () has been shown to prevent the recurrence of duodenal ulcers. Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed duodenal ulcers. Patients remained healed significantly longer and the number of recurrences of duodenal ulcers was significantly less in patients treated with Lansoprazole () than in patients treated with placebo over a 12 month period (Table 13).
In trial #2, no significant difference was noted between Lansoprazole () 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 4 and 8 weeks was significantly higher with Lansoprazole () 15 mg and 30 mg once a day than with placebo (Table 14).
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.
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 Lansoprazole () than with the active control. A total of 711 patients were enrolled in the study, and 701 patients were treated. Patients ranged in age from 18 to 88 years (median age 59 years), with 67% female patients and 33% male patients. Race was distributed as follows: 87% Caucasian, 8% Black, 5% Other. There was no statistically significant difference between Lansoprazole () 30 mg daily and the active control on symptom relief (i.e., abdominal pain) (Table 15).
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 mg or 30 mg of Lansoprazole () than placebo. A total of 537 patients were enrolled in the study, and 535 patients were treated. Patients ranged in age from 23 to 89 years (median age 60 years), with 65% female patients and 35% male patients. Race was distributed as follows: 90% Caucasian, 6% Black, 4% other. The 30 mg dose of Lansoprazole () demonstrated no additional benefit in risk reduction of the NSAID-associated gastric ulcer than the 15 mg dose (Table 16).
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 17 and in Figures 1 and 2:
In two U.S., multicenter double-blind, ranitidine-controlled studies of 925 total patients with frequent GERD symptoms, but no esophageal erosions by endoscopy, Lansoprazole () 15 mg was superior to ranitidine 150 mg (twice daily) in decreasing the frequency and severity of day and night heartburn associated with GERD for the 8-week treatment period. No significant additional benefit from Lansoprazole () 30 mg once daily was observed.
In a U.S. multicenter, double-blind, placebo-controlled study of 269 patients entering with an endoscopic diagnosis of esophagitis with mucosal grading of 2 or more and grades 3 and 4 signifying erosive disease, the percentages of patients with healing are presented in Table 18:
In this study, all Lansoprazole () groups reported significantly greater relief of heartburn and less day and night abdominal pain along with fewer days of antacid use and fewer antacid tablets taken per day than the placebo group. Although all doses were effective, the earlier healing in the higher two doses suggests 30 mg daily as the recommended dose.
Lansoprazole () was also compared in a U.S. multicenter, double-blind study to a low dose of ranitidine in 242 patients with erosive reflux esophagitis. Lansoprazole () at a dose of 30 mg was significantly more effective than ranitidine 150 mg twice daily as shown below (Table 19).
In addition, patients treated with Lansoprazole () reported less day and nighttime heartburn and took less antacid tablets for fewer days than patients taking ranitidine 150 mg twice daily.
Although this study demonstrates effectiveness of Lansoprazole () in healing erosive esophagitis, it does not represent an adequate comparison with ranitidine because the recommended ranitidine dose for esophagitis is 150 mg 4 times daily, twice the dose used in this study.
In the two trials described and in several smaller studies involving patients with moderate to severe erosive esophagitis, Lansoprazole () produced healing rates similar to those shown above.
In a U.S. multicenter, double-blind, active-controlled study, 30 mg of Lansoprazole () was compared with ranitidine 150 mg twice daily in 151 patients with erosive reflux esophagitis that was poorly responsive to a minimum of 12 weeks of treatment with at least one H-receptor antagonist given at the dose indicated for symptom relief or greater, namely, cimetidine 800 mg/day, ranitidine 300 mg/day, famotidine 40 mg/day or nizatidine 300 mg/day. Lansoprazole () 30 mg was more effective than ranitidine 150 mg twice daily in healing reflux esophagitis, and the percentage of patients with healing were as follows. This study does not constitute a comparison of the effectiveness of histamine H-receptor antagonists with Lansoprazole () , as all patients had demonstrated unresponsiveness to the histamine H-receptor antagonist mode of treatment. It does indicate, however, that Lansoprazole () may be useful in patients failing on a histamine H-receptor antagonist (Table 20).
Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed esophagitis. Patients remained in remission significantly longer and the number of recurrences of erosive esophagitis was significantly less in patients treated with Lansoprazole () than in patients treated with placebo over a 12-month period (Table 21).
Regardless of initial grade of erosive esophagitis, Lansoprazole () 15 mg and 30 mg were similar in maintaining remission.
In a U.S., randomized, double-blind, study, Lansoprazole () 15 mg daily (n = 100) was compared with ranitidine 150 mg twice daily (n = 106), at the recommended dosage, in patients with endoscopically-proven healed erosive esophagitis over a 12-month period. Treatment with Lansoprazole () resulted in patients remaining healed (Grade 0 lesions) of erosive esophagitis for significantly longer periods of time than those treated with ranitidine (p
In open studies of 57 patients with pathological hypersecretory conditions, such as Zollinger-Ellison syndrome (ZES) with or without multiple endocrine adenomas, Lansoprazole () significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia and pain. Doses ranging from 15 mg every other day to 180 mg per day maintained basal acid secretion below 10 mEq/hr in patients without prior gastric surgery and below 5 mEq/hr in patients with prior gastric surgery.
Initial doses were titrated to the individual patient need, and adjustments were necessary with time in some patients. Lansoprazole () was well tolerated at these high dose levels for prolonged periods (greater than 4 years in some patients). In most ZES patients, serum gastrin levels were not modified by Lansoprazole () . However, in some patients, serum gastrin increased to levels greater than those present prior to initiation of Lansoprazole () therapy.
Lansoprazole () References
1. National Committee for Clinical Laboratory Standards. Summary Minutes, Subcommittee on Antimicrobial Susceptibility Testing, Tampa, FL, January 11-13, 1998.
Lansoprazole () How Supplied/storage And Handling
Lansoprazole () delayed release capsules USP, 15 mg are white to pale yellow colored enteric coated pellets filled in size ‘3’ hard gelatin capsules with opaque pink colored cap and opaque green colored body, imprinted ‘RDY’ on cap and ‘398’ on body with white ink. They are supplied in unit dose packages of 100 (10x10) NDC 68084-467-01.
Lansoprazole () delayed release capsules USP, 30 mg are white to pale yellow colored enteric coated pellets filled in size ‘1’ hard gelatin capsules with opaque pink colored cap and opaque black colored body, imprinted ‘RDY’ on cap and ‘399’ on body with white ink. They are supplied in unit dose packages of 100 (10x10) NDC 68084-468-01.
Lansoprazole () Patient Counseling Information
Patient should be informed of the following:
Lansoprazole ()
Lansoprazole ()
Lansoprazole ()
