Prevacid Information
Prevacid (Lansoprazole) Indications And Usage
Triple Therapy: Prevacid (Lansoprazole) /amoxicillin /clarithromycin
Prevacid (Lansoprazole) in combination with amoxicillin plus clarithromycin as triple therapy is indicated for the treatment of patients with infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) to eradicate Eradication of has been shown to reduce the risk of duodenal ulcer recurrence.
Please refer to the full prescribing information for amoxicillin and clarithromycin.
Dual Therapy: Prevacid (Lansoprazole) /amoxicillin
Prevacid (Lansoprazole) in combination with amoxicillin as dual therapy is indicated for the treatment of patients with infection and duodenal ulcer disease (active or one-year history of a duodenal ulcer) (see the clarithromycin package insert, MICROBIOLOGY section). Eradication of has been shown to reduce the risk of duodenal ulcer recurrence.
Please refer to the full prescribing information for amoxicillin.
Short-Term Treatment of Symptomatic GERD
Prevacid (Lansoprazole) is indicated for the treatment of heartburn and other symptoms associated with GERD.
Short-Term Treatment of Erosive Esophagitis
Prevacid (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 Prevacid (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 Prevacid (Lansoprazole) may be considered.
Prevacid (Lansoprazole) Dosage And Administration
Prevacid (Lansoprazole) is available as a capsule, orally disintegrating tablet and oral suspension, and is available in 15 mg and 30 mg strengths. Directions for use specific to the route and available methods of administration for each of these dosage forms is presented below. Prevacid (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) .
Administration Options
Prevacid (Lansoprazole) Delayed-Release Capsules - Oral Administration
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
Prevacid (Lansoprazole) Capsules - Nasogastric Tube Administration
Prevacid (Lansoprazole) SoluTab™ Delayed-Release Orally Disintegrating Tablets
Prevacid (Lansoprazole) for Delayed-Release Oral Suspension
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. The adverse reaction profiles for Prevacid (Lansoprazole) Delayed-Release Capsules and Prevacid (Lansoprazole) for Delayed-Release Oral Suspension are similar. 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.
Triple Therapy:
The most frequently reported adverse reactions 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 reactions between the 10- and 14-day triple therapy regimens. No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than with any dual therapy regimen.
Dual Therapy:
The most frequently reported adverse reactions for patients who received Prevacid (Lansoprazole) three times daily plus amoxicillin three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse reactions were observed at significantly higher rates with Prevacid (Lansoprazole) three times daily plus amoxicillin three times daily dual therapy than with Prevacid (Lansoprazole) alone.
For information on adverse reactions with amoxicillin or clarithromycin, refer to their full prescribing information, ADVERSE REACTIONS sections.
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.
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) Use In Specific Populations
Teratogenic effects
Pregnancy Category B. Reproduction studies have been performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day [49 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 (19 times the recommended human dose based on BSA) 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.
See full prescribing information for clarithromycin before using in pregnant women.
Neonate to less than 1 year of age
The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged less than 28 days and 1 to 11 months. Compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized AUC values 2.04- and 1.88-fold higher at doses of 0.5 mg/kg/day and1 mg/kg/day, respectively). Infants aged ≤ 10 weeks had clearance and exposure values that were similar to neonates. Infants aged greater than 10 weeks who received 1 mg/kg/day had mean AUC values that were similar to adults who received a 30 mg dose.
Lansoprazole was not found to be effective in a U.S. and Polish 4 week multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic GERD based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative GERD management (i.e., non-pharmacologic intervention) for 7 to 14 days. Patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤ 10 weeks of age or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to 4 weeks of double-blind treatment.
The primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding.
There was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups).
There were no adverse events reported in pediatric clinical studies (1 month to less than 12 months of age) that were not previously observed in adults.
Based on the results of the Phase 3 efficacy study, lansoprazole was not shown to be effective. Therefore, these results do not support the use of lansoprazole in treating symptomatic GERD in infants.
One to 11 years of age
In an uncontrolled, open-label, U.S. multicenter study, 66 pediatric patients (1 to 11 years of age) with GERD were assigned, based on body weight, to receive an initial dose of either Prevacid (Lansoprazole) 15 mg daily if ≤ 30 kg or Prevacid (Lansoprazole) 30 mg daily if greater than 30 kg administered for 8 to 12 weeks. The Prevacid (Lansoprazole) dose was increased (up to 30 mg twice daily) 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 non-erosive GERD and 42% had erosive esophagitis (assessed by endoscopy).
After 8 to 12 weeks of Prevacid (Lansoprazole) treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of GERD symptoms.
Twenty-one of 27 erosive esophagitis patients were healed at 8 weeks and 100% of patients were healed at 12 weeks by endoscopy (Table 2).
In a study of 66 pediatric patients in the age group 1 year to 11 years old after treatment with Prevacid (Lansoprazole) given orally in doses of 15 mg daily to 30 mg twice daily, 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 (25-75 percentile) of 71-130 pg/ mL] at the final visit.
The pediatric safety of Prevacid (Lansoprazole) Delayed-Release Capsules has been assessed in 66 pediatric patients aged 1 to 11 years of age. Of the 66 patients with GERD 85% (56/66) took Prevacid (Lansoprazole) for 8 weeks and 15% (10/66) took it for 12 weeks.
The most frequently reported (2 or more patients) treatment-related adverse reactions in patients 1 to 11 years of age (N=66) were constipation (5%) and headache (3%).
Twelve to 17 years of age
In an uncontrolled, open-label, U.S. multicenter study, 87 adolescent patients (12 to 17 years of age) with symptomatic GERD were treated with Prevacid (Lansoprazole) for 8 to 12 weeks. Baseline upper endoscopies classified these patients into two groups: 64 (74%) nonerosive GERD and 23 (26%) erosive esophagitis (EE). The nonerosive GERD patients received Prevacid (Lansoprazole) 15 mg daily for 8 weeks and the EE patients received Prevacid (Lansoprazole) 30 mg daily for 8 to 12 weeks. At baseline, 89% of these patients had mild to moderate overall GERD symptoms (assessed by investigator interviews). During 8 weeks of Prevacid (Lansoprazole) treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of GERD symptoms based on diary results.
Twenty-one of 22 (95.5%) adolescent erosive esophagitis patients were healed after 8 weeks of Prevacid (Lansoprazole) treatment. One patient remained unhealed after 12 weeks of treatment (Table 3).
In these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/mL at baseline to 64 pg/mL [interquartile range (25 – 75 percentile) of 44 – 88 pg/mL] at the final visit. (Normal serum gastrin levels are 25 to 111 pg/mL).
The safety of Prevacid (Lansoprazole) Delayed-Release Capsules has been assessed in these 87 adolescent patients. Of the 87 adolescent patients with GERD, 6% (5/87) took Prevacid (Lansoprazole) for less than 6 weeks, 93% (81/87) for 6-10 weeks, and 1% (1/87) for greater than 10 weeks.
The most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). Treatment-related dizziness, reported in this package insert as occurring in less than 1% of adult patients, was reported in this study by 3 adolescent patients with nonerosive GERD, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting).
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 1600 times the 30 mg human dose based on BSA) and in mice (about 800 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 Capsules, Prevacid (Lansoprazole) for Delayed-Release Oral Suspension and 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, in delayed-release orally disintegrating tablets for oral administration and in a packet for delayed-release oral suspension.
The delayed-release capsules are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per capsule. Each delayed-release capsule contains enteric-coated granules consisting of 15 mg or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: 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) for Delayed-Release Oral Suspension are available in two dosage strengths: 15 mg and 30 mg of lansoprazole per packet. Each packet of delayed-release oral suspension contains enteric-coated granules consisting of 15 or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients (inactive granules): mannitol, confectioner's sugar, xanthan gum, crospovidone, citric acid, magnesium stearate, sodium citrate, artificial strawberry flavor, colloidal silicon dioxide, ferric oxide and docusate sodium. The lansoprazole granules and inactive granules, present in unit dose packets, are constituted with water to form a suspension and consumed orally.
Prevacid (Lansoprazole) Clinical Pharmacology
Antisecretory Activity:
The intragastric pH results of a five-day, pharmacodynamic, crossover study of 15 mg and 30 mg of once daily lansoprazole are presented in Table 4:
After the initial dose in this study, increased gastric pH was seen within 1-2 hours with 30 mg of lansoprazole and 2-3 hours with 15 mg of lansoprazole. After multiple daily dosing, increased gastric pH was seen within the first hour post-dosing with 30 mg of lansoprazole and within 1-2 hours post-dosing with 15 mg of lansoprazole.
Acid suppression may enhance the effect of antimicrobials in eradicating (). The percentage of time gastric pH was elevated above 5 and 6 was evaluated in a crossover study of Prevacid (Lansoprazole) given daily, twice daily and three times daily (Table 5).
The inhibition of gastric acid secretion as measured by intragastric pH gradually returned to normal over two to four days after multiple doses. There was no indication of rebound gastric acidity.
Enterochromaffin-like (ECL) Cell Effects
During lifetime exposure of rats with up to 150 mg/kg/day of lansoprazole dosed seven days per week, marked hypergastrinemia was observed followed by ECL cell proliferation and formation of carcinoid tumors, especially in female rats. Gastric biopsy specimens from the body of the stomach from approximately 150 patients treated continuously with lansoprazole for at least one year did not show evidence of ECL cell effects similar to those seen in rat studies. Longer term data are needed to rule out the possibility of an increased risk of the development of gastric tumors in patients receiving long-term therapy with lansoprazole.
Other Gastric Effects in Humans
Lansoprazole did not significantly affect mucosal blood flow in the fundus of the stomach. Due to the normal physiologic effect caused by the inhibition of gastric acid secretion, a decrease of about 17% in blood flow in the antrum, pylorus, and duodenal bulb was seen. Lansoprazole significantly slowed the gastric emptying of digestible solids. Lansoprazole increased serum pepsinogen levels and decreased pepsin activity under basal conditions and in response to meal stimulation or insulin injection. As with other agents that elevate intragastric pH, increases in gastric pH were associated with increases in nitrate-reducing bacteria and elevation of nitrite concentration in gastric juice in patients with gastric ulcer. No significant increase in nitrosamine concentrations was observed.
Serum Gastrin Effects
In over 2100 patients, median fasting serum gastrin levels increased 50% to 100% from baseline but remained within normal range after treatment with 15 to 60 mg of oral lansoprazole. These elevations reached a plateau within two months of therapy and returned to pretreatment levels within four weeks after discontinuation of therapy.
Endocrine Effects
Human studies for up to one year have not detected any clinically significant effects on the endocrine system. Hormones studied include testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), prolactin, cortisol, estradiol, insulin, aldosterone, parathormone, glucagon, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and somatotropic hormone (STH). Lansoprazole in oral doses of 15 to 60 mg for up to one year had no clinically significant effect on sexual function. In addition, lansoprazole in oral doses of 15 to 60 mg for two to eight weeks had no clinically significant effect on thyroid function. In 24-month carcinogenicity studies in Sprague-Dawley rats with daily lansoprazole dosages up to 150 mg/kg, proliferative changes in the Leydig cells of the testes, including benign neoplasm, were increased compared to control rats.
Other Effects
No systemic effects of lansoprazole on the central nervous system, lymphoid, hematopoietic, renal, hepatic, cardiovascular, or respiratory systems have been found in humans. Among 56 patients who had extensive baseline eye evaluations, no visual toxicity was observed after lansoprazole treatment (up to 180 mg/day) for up to 58 months. After lifetime lansoprazole exposure in rats, focal pancreatic atrophy, diffuse lymphoid hyperplasia in the thymus, and spontaneous retinal atrophy were seen.
Microbiology
Lansoprazole, clarithromycin and/or amoxicillin have been shown to be active against most strains of and in clinical infections as described in the INDICATIONS AND USAGE section.
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 of 957 patients (2.2%) by E-test and 2 of 100 patients (2.0%) by agar dilution had amoxicillin pretreatment MICs of greater than 0.25 µg/mL. One patient on the 14-day triple therapy regimen had an unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of greater than 256 µg/mL by E-test and the patient was eradicated of (Table 6)
Patients not eradicated of following lansoprazole/amoxicillin/clarithromycin triple therapy will likely have clarithromycin resistant Therefore, for those patients who fail therapy, clarithromycin susceptibility testing should be done when possible. Patients with clarithromycin resistant 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:
H. pylori
H. pylori
H. pylori
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 following criteria (Table 7):
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 following MIC values (Table 8):
Absorption:
max
max
Distribution:
Metabolism:
+
+
Elimination:
14
Pediatric Use:
One to 17 years of age
The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged 1 to 11 years and 12 to 17 years in two separate clinical studies. In children aged 1 to 11 years, lansoprazole was dosed 15 mg daily for subjects weighing ≤ 30 kg and 30 mg daily for subjects weighing greater than 30 kg. Mean Cand AUC values observed on Day 5 of dosing were similar between the two dose groups and were not affected by weight or age within each weight-adjusted dose group used in the study. In adolescent subjects aged 12 to 17 years, subjects were randomized to receive lansoprazole at 15 mg or 30 mg daily. Mean C and AUC values of lansoprazole were not affected by body weight or age; and nearly dose-proportional increases in mean C and AUC values were observed between the two dose groups in the study. Overall, lansoprazole pharmacokinetics in pediatric patients aged 1 to 17 years were similar to those observed in healthy adult subjects.
Neonate to less than one year of age
Refer to Section 8.4 for the pharmacokinetics of lansoprazole in pediatric patients with GERD aged less than 28 days and 1 to 11 months.
Geriatric Use:
[See Use in Specific Populations (8.5)].
Renal Impairment:
[See Use in Specific Populations (8.6])
max
max
max
max
Hepatic Impairment:
[See Use in Specific Populations (8.7)].
Gender
[See Use in Specific Populations (8.5)]
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.
Atazanavir:
Theophylline:
Warfarin:
Methotrexate and 7-hydromethotrexate:
Amoxicillin:
Sucralfate:
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 4-6 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)
Symptomatic GERD:
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.
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<0.001). In addition, Prevacid (Lansoprazole) was significantly more effective than ranitidine in providing complete relief of both daytime and nighttime heartburn. Patients treated with Prevacid (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 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) for Delayed-Release Oral Suspension contains white to pale brownish lansoprazole granules and inactive pink granules in a unit dose packet.
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.
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:
They are supplied as follows:
Prevacid (Lansoprazole) Patient Counseling Information
Patient should be informed of the following:
Administration Options
USE IN OTHER FOODS AND LIQUIDS HAS NOT BEEN STUDIED CLINICALLY AND IS THEREFORE NOT RECOMMENDED.
Prevacid (Lansoprazole) Label Image For Mg Count Bottle
Prevacid (Lansoprazole) Manufacturer Information
Manufactured By:
TAKEDA PHARMACEUTICALS AMERICA, INC.DISTRIBUTED BY: TAKEDA PHARMACEUTICALS AMERICA, INC.DEERFIELD, IL 60015
64764-046-19 For 0339-6489-11 Prevacid (Lansoprazole) 30 mg
64764-046-19 For 0339-6489-06 Prevacid (Lansoprazole) 30 mg
Repackaged By:
Caremark L.L.C.
1100 Lakeside Drive
Gurnee, Illinois 60031
United States
