Prevacid Information
Prevacid (Lansoprazole) Dosage And Administration
Prevacid (Lansoprazole) is available as a capsule and an orally disintegrating tablet, and is available in 15 mg and 30 mg strengths. Directions for use specific to the route and available methods of administration for each of these dosage forms is presented below. Prevacid (Lansoprazole) should be taken before eating. Prevacid (Lansoprazole) products SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with Prevacid (Lansoprazole) .
Prevacid (Lansoprazole) Contraindications
Prevacid (Lansoprazole) is contraindicated in patients with known severe hypersensitivity to any component of the formulation of Prevacid (Lansoprazole) .
For information on contraindications for amoxicillin or clarithromycin, refer to their full prescribing information, CONTRAINDICATIONS sections.
Prevacid (Lansoprazole) Warnings And Precautions
Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.
For information on warnings and precautions for amoxicillin or clarithromycin, refer to their full prescribing information, WARNINGS and PRECAUTIONS sections.
Prevacid (Lansoprazole) Adverse Reactions
Worldwide, over 10,000 patients have been treated with Prevacid (Lansoprazole) in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, Prevacid (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 Prevacid (Lansoprazole) -treated patients and occurred at a greater rate in Prevacid (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 Prevacid (Lansoprazole) , but higher in the patients who received 60 mg of Prevacid (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 Prevacid (Lansoprazole) for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with Prevacid (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 Prevacid (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 Prevacid (Lansoprazole) in domestic trials are shown below:
Body as a Whole
Cardiovascular System –
Digestive System –
Endocrine System –
Hemic and Lymphatic System –
Metabolic and Nutritional Disorders –
Musculoskeletal System –
Nervous System –
Respiratory System –
Skin and Appendages –
Special Senses –
Urogenital System –
Additional adverse experiences have been reported since Prevacid (Lansoprazole) has been marketed. The majority of these cases are foreign-sourced and a relationship to Prevacid (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 Prevacid (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% (11/2677) patients, who received placebo and Prevacid (Lansoprazole) , 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 (Lansoprazole) reported jaundice at any time during the study.
In clinical trials using combination therapy with Prevacid (Lansoprazole) plus amoxicillin and clarithromycin, and Prevacid (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.
Prevacid (Lansoprazole) Drug Interactions
Drugs with pH-Dependent Absorption Kinetics
Prevacid (Lansoprazole) causes long-lasting inhibition of gastric acid secretion. Prevacid (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, Prevacid (Lansoprazole) and other PPIs should not be co-administered with atazanavir .
It is theoretically possible that Prevacid (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).
Warfarin
In a study of healthy subjects, co-administration of single or multiple 60 mg doses of Prevacid (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 .
Tacrolimus
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.
Theophylline
A minor increase (10%) in the clearance of theophylline was observed following the administration of Prevacid (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 Prevacid (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.
Prevacid (Lansoprazole) Overdosage
Prevacid (Lansoprazole) is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of Prevacid (Lansoprazole) with no adverse reaction. Oral Prevacid (Lansoprazole) doses up to 5000 mg/kg in rats [approximately 1300 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.
Prevacid (Lansoprazole) Description
The active ingredient in Prevacid (Lansoprazole) Delayed-Release Capsulesand Prevacid (Lansoprazole) 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 CHFNOS with a molecular weight of 369.37. Prevacid (Lansoprazole) 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 (Lansoprazole) is supplied in delayed-release capsules and in delayed-release orally disintegrating tablets for oral administration.
The delayed-release capsules are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per capsule. Each delayed-release capsule contains enteric-coated granules consisting of 15 mg or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: sugar sphere, sucrose, methacrylic acid copolymer, low substituted hydroxypropyl cellulose, starch, magnesium carbonate, talc, polyethylene glycol, titanium dioxide, polysorbate 80, hydroxypropyl cellulose, colloidal silicon dioxide, D&C Red No. 28, FD&C Blue No. 1, FD&C Green No. 3, and FD&C Red No. 40.
Prevacid (Lansoprazole) SoluTab Delayed-Release Orally Disintegrating Tablets are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per tablet. Each delayed-release orally disintegrating tablet contains enteric-coated microgranules consisting of 15 mg or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: mannitol, methacrylic acid, hydroxypropyl cellulose, lactose monohydrate-microcrystalline cellulose sphere, triethyl citrate, crospovidone, polyacrylate, magnesium carbonate, aspartame, glyceryl monostearate, hypromellose, magnesium stearate, citric acid, titanium dioxide, talc, artificial strawberry flavor, polyethylene glycol, polysorbate 80 and ferric oxide.
Prevacid (Lansoprazole) Clinical Pharmacology
It is theoretically possible that Prevacid (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).
Prevacid (Lansoprazole) is metabolized through the cytochrome P system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that Prevacid (Lansoprazole) does not have clinically significant interactions with other drugs metabolized by the cytochrome P system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A.
Prevacid (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.
Prevacid (Lansoprazole) Clinical Studies
Duodenal Ulcer
In a U.S. multicenter, double-blind, placebo-controlled, dose-response (15, 30, and 60 mg of Prevacid (Lansoprazole) 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 (Lansoprazole) than with placebo. There was no evidence of a greater or earlier response with the two higher doses compared with Prevacid (Lansoprazole) 15 mg. Based on this study and the second study described below, the recommended dose of Prevacid (Lansoprazole) in duodenal ulcer is 15 mg per day (Table 9).
Prevacid (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 and 30 mg of Prevacid (Lansoprazole) 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 (Lansoprazole) than with placebo. There was no evidence of a greater or earlier response with the higher dose of Prevacid (Lansoprazole) . Although the 15 mg dose of Prevacid (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 Prevacid (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 Prevacid (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:
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 Prevacid (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).
Long-Term Maintenance Treatment of Duodenal Ulcers
Prevacid (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 Prevacid (Lansoprazole) than in patients treated with placebo over a 12-month period (Table 13) .
In trial #2, no significant difference was noted between Prevacid (Lansoprazole) 15 mg and 30 mg in maintaining remission.
Gastric Ulcer
In a U.S. multicenter, double-blind, placebo-controlled study of 253 patients with endoscopically documented gastric ulcer, the percentage of patients healed at four and eight weeks was significantly higher with Prevacid (Lansoprazole) 15 mg and 30 mg once a day than with placebo (Table 14) .
Patients treated with any Prevacid (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 Prevacid (Lansoprazole) 30 mg was provided by a meta-analysis of published and unpublished data.
Healing of NSAID-Associated Gastric Ulcer
In two U.S. and Canadian multicenter, double-blind, active-controlled studies in patients with endoscopically confirmed NSAID-associated gastric ulcer who continued their NSAID use, the percentage of patients healed after 8 weeks was statistically significantly higher with 30 mg of Prevacid (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 Prevacid (Lansoprazole) 30 mg daily and the active control on symptom relief (i.e., abdominal pain) (Table 15) .
Risk Reduction of NSAID-Associated Gastric Ulcer
In one large U.S., multicenter, double-blind, placebo- and misoprostol-controlled (misoprostol blinded only to the endoscopist) study in patients who required chronic use of an NSAID and who had a history of an endoscopically documented gastric ulcer, the proportion of patients remaining free from gastric ulcer at 4, 8, and 12 weeks was significantly higher with 15 or 30 mg of Prevacid (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 Prevacid (Lansoprazole) demonstrated no additional benefit in risk reduction of the NSAID-associated gastric ulcer than the 15 mg dose (Table 16) .
Gastroesophageal Reflux Disease (GERD)
Erosive Esophagitis
In a U.S. multicenter, double-blind, placebo-controlled study of 269 patients entering with an endoscopic diagnosis of esophagitis with mucosal grading of 2 or more and grades 3 and 4 signifying erosive disease, the percentages of patients with healing are presented in Table 18:
In this study, all Prevacid (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.
Prevacid (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. Prevacid (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 Prevacid (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 Prevacid (Lansoprazole) in healing erosive esophagitis, it does not represent an adequate comparison with ranitidine because the recommended ranitidine dose for esophagitis is 150 mg q.i.d., twice the dose used in this study.
In the two trials described and in several smaller studies involving patients with moderate to severe erosive esophagitis, Prevacid (Lansoprazole) produced healing rates similar to those shown above.
In a U.S. multicenter, double-blind, active-controlled study, 30 mg of Prevacid (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.
Prevacid (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 Prevacid (Lansoprazole) , as all patients had demonstrated unresponsiveness to the histamine H-receptor antagonist mode of treatment. It does indicate, however, that Prevacid (Lansoprazole) may be useful in patients failing on a histamine H-receptor antagonist (Table 20) .
Long-Term Maintenance Treatment of Erosive Esophagitis
Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed esophagitis. Patients remained in remission significantly longer and the number of recurrences of erosive esophagitis was significantly less in patients treated with Prevacid (Lansoprazole) than in patients treated with placebo over a 12-month period (Table 21).
Regardless of initial grade of erosive esophagitis, Prevacid (Lansoprazole) 15 mg and 30 mg were similar in maintaining remission.
In a U.S., randomized, double-blind, study, Prevacid (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 Prevacid (Lansoprazole) resulted in patients remaining healed (Grade 0 lesions) of erosive esophagitis for significantly longer periods of time than those treated with ranitidine (p
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
In open studies of 57 patients with pathological hypersecretory conditions, such as Zollinger-Ellison syndrome (ZES) with or without multiple endocrine adenomas, Prevacid (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 Prevacid (Lansoprazole) was well tolerated at these high dose levels for prolonged periods (greater than four years in some patients). In most ZES patients, serum gastrin levels were not modified by Prevacid (Lansoprazole) . However, in some patients, serum gastrin increased to levels greater than those present prior to initiation of lansoprazole therapy .
Prevacid (Lansoprazole) How Supplied/storage And Handling
Prevacid (Lansoprazole) Delayed-Release Capsules, 15 mg, are opaque, hard gelatin, colored pink and green with "TAP" and "Prevacid (Lansoprazole) 15" imprinted on the capsules. The 30 mg capsules are opaque, hard gelatin, colored pink and black with "TAP" and "Prevacid (Lansoprazole) 30" imprinted on the capsules. They are available as follows:
Prevacid (Lansoprazole) 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:
Prevacid (Lansoprazole) Patient Counseling Information
Patient should be informed of the following:
Prevacid (Lansoprazole)
Prevacid (Lansoprazole) Principal Display Panel - Bag
Prevacid (Lansoprazole) Solutab 30 mg
Lansoprazole
Delayed-Release Orally Disintegrating Tablets
10 Tablets
