Lansoprazole

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.

Lansoprazole is supplied in delayed-release capsule form, for oral administration in two strengths 15 mg and 30 mg.

Lansoprazole delayed-release capsules are available in two strengths: 15 mg and 30 mg of lansoprazole per capsule. Each delayed-release capsule contains lansoprazole delayed-release pellets 8.5% consisting of 15 mg or 30 mg of lansoprazole (active ingredient) and the following inactive ingredients: acetone, hypromellose, isopropyl alcohol, light magnesium carbonate, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, sugar spheres, talc and titanium dioxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Lansoprazole delayed-release capsules belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the (H⁺, K⁺)-ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the parietal cell, lansoprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus. Lansoprazole does not exhibit anticholinergic or histamine type-2 antagonist activity.

12.2 Pharmacodynamics

Antisecretory Activity: After oral administration, lansoprazole was shown to significantly decrease the basal acid output and significantly increase the mean gastric pH and percent of time the gastric pH was greater than 3 and greater than 4. Lansoprazole also significantly reduced meal-stimulated gastric acid output and secretion volume, as well as pentagastrin-stimulated acid output. In patients with hypersecretion of acid, lansoprazole significantly reduced basal and pentagastrin-stimulated gastric acid secretion. Lansoprazole inhibited the normal increases in secretion volume, acidity and acid output induced by insulin.

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

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 Helicobacter pylori in vitro and in clinical infections as described in the INDICATIONS AND USAGE section [see Indications and Usage (1.2)].

Helicobacter pylori Pretreatment Resistance

Clarithromycin pretreatment resistance (≥2.0 mcg/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).

Patients not eradicated of H. pylori following lansoprazole/amoxicillin/clarithromycin triple therapy will likely have clarithromycin resistant H. pylori. Therefore, for those patients who fail therapy, clarithromycin susceptibility testing should be done when possible. Patients with clarithromycin resistant H. pylori should not be treated with lansoprazole/amoxicillin/clarithromycin triple therapy or with regimens which include clarithromycin as the sole antimicrobial agent.

Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes: In the dual and triple therapy clinical trials, 82.6% (195/236) of the patients that had pretreatment amoxicillin susceptible MICs (≤0.25 mcg/mL) were eradicated of H. pylori. Of those with pretreatment amoxicillin MICs of greater than 0.25 mcg/mL, three of six had the H. pylori eradicated. A total of 30% (21/70) of the patients failed lansoprazole 30 mg three times daily/amoxicillin 1 g three times daily dual therapy and a total of 12.8% (22/172) of the patients failed the 10- and 14-day triple therapy regimens. Post-treatment susceptibility results were not obtained on 11 of the patients who failed therapy. Nine of the 11 patients with amoxicillin post-treatment MICs that failed the triple therapy regimen also had clarithromycin resistant H. pylori isolates.

Susceptibility Test for Helicobacter pylori: For susceptibility testing information about Helicobacter pylori, see Microbiology section in prescribing information for clarithromycin and amoxicillin.

12.3 Pharmacokinetics

Lansoprazole delayed-release capsules contain an enteric-coated granule formulation of lansoprazole. Absorption of lansoprazole begins only after the granules leave the stomach. Absorption is rapid, with mean peak plasma levels of lansoprazole occurring after approximately 1.7 hours. After a single-dose administration of 15 mg to 60 mg of oral lansoprazole, the peak plasma concentrations (C_max) of lansoprazole and the area under the plasma concentration curves (AUCs) of lansoprazole were approximately proportional to the administered dose. Lansoprazole does not accumulate and its pharmacokinetics are unaltered by multiple dosing.

Absorption: The absorption of lansoprazole is rapid, with the mean C_max occurring approximately 1.7 hours after oral dosing, and the absolute bioavailability is over 80%. In healthy subjects, the mean (±SD) plasma half-life was 1.5 (±1.0) hours. Both the C_max and AUC are diminished by about 50% to 70% if lansoprazole is given 30 minutes after food, compared to the fasting condition. There is no significant food effect if lansoprazole is given before meals.

Distribution: Lansoprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 0.05 to 5.0 mcg/mL.

Specific Populations

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 C_max and 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_max and AUC values of lansoprazole were not affected by body weight or age; and nearly dose-proportional increases in mean C_max 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: The clearance of lansoprazole is decreased in the elderly, with elimination half-life increased approximately 50% to 100%. Because the mean half-life in the elderly remains between 1.9 to 2.9 hours, repeated once daily dosing does not result in accumulation of lansoprazole. Peak plasma levels were not increased in the elderly. No dosage adjustment is necessary in the elderly [see Use in Specific Populations (8.5)].

Renal Impairment: In patients with severe renal impairment, plasma protein binding decreased by 1.0% to1.5% after administration of 60 mg of lansoprazole. Patients with renal impairment had a shortened elimination half-life and decreased total AUC (free and bound). The AUC for free lansoprazole in plasma, however, was not related to the degree of renal impairment; and the C_max and T_max (time to reach the maximum concentration) were not different than the C_max and T_max from subjects with normal renal function. No dosage adjustment is necessary in patients with renal impairment [see Use in Specific Populations (8.6)].

Hepatic Impairment: In patients with various degrees of chronic hepatic impairment, the mean plasma half-life of lansoprazole was prolonged from 1.5 hours to 3.2 to 7.2 hours. An increase in the mean AUC of up to 500% was observed at steady state in hepatically-impaired patients compared to healthy subjects. Consider dose reduction in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

Gender: In a study comparing 12 male and 6 female human subjects who received lansoprazole, no gender differences were found in pharmacokinetics and intragastric pH results [see Use in Specific Populations (8.8)].

Drug-Drug Interactions

Lansoprazole delayed-release capsules 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 delayed-release capsules are metabolized through the cytochrome P₄₅₀ system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole delayed-release capsules do 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.

Atazanavir: Lansoprazole delayed-release capsule causes long-lasting inhibition of gastric acid secretion. Lansoprazole delayed-release capsules substantially decreases 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 delayed-release capsules, or other proton pump inhibitors, should not be co-administered with atazanavir.

Theophylline: When lansoprazole delayed-release capsules were administered concomitantly with theophylline (CYP1A2, CYP3A), a minor increase (10%) in the clearance of theophylline was seen. Because of the small magnitude and the direction of the effect on theophylline clearance, this interaction is unlikely to be of clinical concern. Nonetheless, individual patients may require additional titration of their theophylline dosage when lansoprazole delayed-release capsules are started or stopped to ensure clinically effective blood levels.

Warfarin: In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased International Normalized Ratio (INR) and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole delayed-release capsules, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.

Methotrexate and 7-hydromethotrexate: In an open-label, single-arm, eight-day, pharmacokinetic study of 28 adult rheumatoid arthritis patients (who required the chronic use of 7.5 to 15 mg of methotrexate given weekly), administration of 7 days of naproxen 500 mg twice daily and lansoprazole delayed-release capsules 30 mg daily had no effect on the pharmacokinetics of methotrexate and 7-hydroxymethotrexate. While this study was not designed to assess the safety of this combination of drugs, no major adverse reactions were noted. However, this study was conducted with low doses of methotrexate. A drug interaction study with high doses of methotrexate has not been conducted.

Amoxicillin: Lansoprazole delayed-release capsules have also been shown to have no clinically significant interaction with amoxicillin. 

Sucralfate: In a single-dose crossover study examining lansoprazole delayed-release capsules 30 mg and omeprazole 20 mg each administered alone and concomitantly with sucralfate 1 gram, absorption of the proton pump inhibitors was delayed and their bioavailability was reduced by 17% and 16%, respectively, when administered concomitantly with sucralfate. Therefore, proton pump inhibitors should be taken at least 30 minutes prior to sucralfate. In clinical trials, antacids were administered concomitantly with lansoprazole delayed-release capsules and there was no evidence of a change in the efficacy of lansoprazole delayed-release capsules.

Clopidogrel: Clopidogrel is metabolized to its active metabolite in part by CYP2C19. A study of healthy subjects who were CYP2C19 extensive metabolizers, receiving once daily administration of clopidogrel 75 mg alone or concomitantly with lansoprazole delayed-release capsules 30mg (n=40), for 9 days was conducted. The mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (mean AUC ratio was 86%, with 90% Cl of 80 to 92%) when lansoprazole delayed-released capsules was coadministered compared to administration of clopidogrel alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 mcM ADP) was related to the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

In two 24-month carcinogenicity studies, Sprague-Dawley rats were treated with oral lansoprazole doses of 5 to 150 mg/kg/day, about 1 to 40 times the exposure on a body surface (mg/m²) basis of a 50 kg person of average height [1.46 m² body surface area (BSA)] given the recommended human dose of 30 mg/day. 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.

Lansoprazole was positive in the Ames test and the in vitro human lymphocyte chromosomal aberration assays. Lansoprazole was not genotoxic in the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo mouse micronucleus test, or the rat bone marrow cell chromosomal aberration test

13.2 Animal Toxicology and/or Pharmacology

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.

14 CLINICAL STUDIES

Duodenal Ulcer

Lansoprazole delayed-release capsules 15 mg were significantly more effective than placebo in relieving day and nighttime abdominal pain and in decreasing the amount of antacid taken per day.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Triple therapy was shown to be more effective than all possible dual therapy combinations. Dual therapy was shown to be more effective than both monotherapies. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Long-Term Maintenance Treatment of Duodenal Ulcers

In trial #2, no significant difference was noted between lansoprazole delayed-release capsules 15 mg and 30 mg in maintaining remission. 

Gastric Ulcer

Patients treated with any lansoprazole delayed-release capsules 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.

Risk Reduction of NSAID-Associated Gastric Ulcer

(p<0.001) Lansoprazole delayed-release capsules15 mg daily versus placebo; Lansoprazole delayed-release capsules30 mg daily versus placebo; and misoprostol 200 mcg four times daily versus placebo.

Gastroesophageal Reflux Disease (GERD)

Symptomatic GERD: In a U.S. multicenter, double-blind, placebo-controlled study of 214 patients with frequent GERD symptoms, but no esophageal erosions by endoscopy, significantly greater relief of heartburn associated with GERD was observed with the administration of lansoprazole 15 mg once daily up to 8 weeks than with placebo. No significant additional benefit from lansoprazole 30 mg once daily was observed. 

In this study, all lansoprazole delayed-release capsules 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 delayed-release capsules were also compared in a U.S. multicenter, double-blind study to a low dose of ranitidine in 242 patients with erosive reflux esophagitis.

In addition, patients treated with lansoprazole delayed-release capsules reported less day and nighttime heartburn and took less antacid tablets for fewer days than patients taking ranitidine 150 mg twice daily.

In the two trials described and in several smaller studies involving patients with moderate to severe erosive esophagitis, lansoprazole delayed-release capsules produced healing rates similar to those shown above.

Regardless of initial grade of erosive esophagitis, lansoprazole delayed-release capsules 15 mg and 30 mg were similar in maintaining remission.

In open studies of 57 patients with pathological hypersecretory conditions, such as Zollinger-Ellison syndrome (ZES) with or without multiple endocrine adenomas, lansoprazole delayed-release capsules significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia and pain. Doses ranging from 15 mg every other day to 180 mg per day maintained basal acid secretion below 10 mEq/hr in patients without prior gastric surgery and below 5 mEq/hr in patients with prior gastric surgery.

Initial doses were titrated to the individual patient need, and adjustments were necessary with time in some patients [see Dosage and Administration (2.1)]. Lansoprazole delayed-release capsules were 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 lansoprazole delayed-release capsules. However, in some patients, serum gastrin increased to levels greater than those present prior to initiation of lansoprazole therapy [see Indications and Usage (1.9)].

15 REFERENCES

1.  National Committee for Clinical Laboratory Standards. Summary Minutes, Subcommittee on Antimicrobial Susceptibility Testing, Tampa, FL, January 11-13, 1998.

16 HOW SUPPLIED/STORAGE AND HANDLING

Lansoprazole delayed-release capsules 15 mg, contains white to off white coloured spherical shaped pellets filled in size '3’ capsules with green colour body and pink colour cap, printed NATCO on cap and 15 on body with white ink.

Lansoprazole delayed-release capsules 30 mg, contains white to off white coloured spherical shaped pellets filled in size '1’ capsules with dark blue colour body and pink colour cap, printed NATCO on cap and 30 on body with white ink.

NDC-51991-772-33 Bottle of 30-30 mg capsules

NDC-51991-772-90 Bottle of 90-30 mg capsules

NDC-51991-772-01 Bottle of 100-30 mg capsules

NDC-51991-772-05 Bottle of 500-30 mg capsules

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

[See FDA-Approved Medication Guide and Patient Instructions for Use]

Patient should be informed of the following:

·      Advise patients to immediately report and seek care for diarrhea that does not improve. This may be sign of Clostridium difficile associated diarrhea [see Warnings and Precautions (5.2)].

·      Advise patients to immediately report and seek care for any cardiovascular or neurological symptoms including palpitations, dizziness, seizures, and tetany as these may be signs of hypomagnesemia [see Warnings and Precautions (5.4)].

Information for Patients

Lansoprazole delayed-release capsules are available as a capsule, and are 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 [see Dosage and Administration (2.3)].

·            Lansoprazole delayed-release capsules should be taken before eating.

·            Lansoprazole delayed-release capsules SHOULD NOT BE CRUSHED OR CHEWED. 

Administration Options

Lansoprazole Delayed-Release Capsules – Oral Administration

·                        Lansoprazole delayed-release capsules should be swallowed whole.

·      Alternatively, for patients who have difficulty swallowing capsules, lansoprazole delayed-release capsules can be opened and administered as follows:

o  Open capsule.

o  Sprinkle intact granules on one tablespoon of applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.

o  Swallow immediately.

·      Lansoprazole delayed-release capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice and administered as follows:

o  Open capsule.

o  Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately 2 ounces).

o  Mix briefly.

o  Swallow immediately.

o  To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.  

Lansoprazole Delayed-Release Capsules – Nasogastric Tube (≥16 French) Administration

·      For patients who have a nasogastric tube in place,lansoprazole delayed-release capsules can be administered as follows:

o  Open capsule.

o  Mix intact granules into 40 ml of apple juice. DO NOT USE OTHER LIQUIDS.

o  Inject through the nasogastric tube into the stomach.

o  Flush with additional apple juice to clear the tube.

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

MEDICATION GUIDE

Read this Medication Guide before you start taking lansoprazole delayed-release capsules and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information that I should know about lansoprazole delayed-release capsules ?

Lansoprazole delayed-release capsulesmay help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

Lansoprazole delayed-release capsules can cause serious side effects, including:

· Diarrhea. Lansoprazole delayed-release capsulesmay increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection (Clostridium difficile) in your intestines.

Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.

· Bone fractures. People who take multiple daily doses of proton pump inhibitor medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist or spine. You should take lansoprazole delayed-release capsulesexactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take lansoprazole delayed-release capsules.

Lansoprazole delayed-release capsulescan have other serious side effects. See “What are the possible side effects of Lansoprazole delayed-release capsules?”

What are lansoprazole delayed-release capsules?

Lansoprazole delayed-release capsule is a prescription medicine called a proton pump inhibitor (PPI). Lansoprazole delayed-release capsules reduce the amount of acid in your stomach.

Lansoprazole delayed-release capsules are used in adults:

·  for 4 weeks for the healing and symptom  relief of duodenal ulcers. The duodenal area is the area where food passes when it leaves the stomach.

·  with certain antibiotics to treat an infection called H. pylori. Sometimes H. pylori bacteria can cause duodenal ulcers. The infection needs to be treated to prevent ulcers from coming back.

· for continued healing of duodenal ulcers.

· for up to 8 weeks to heal stomach ulcers.

· for up to 8 weeks to heal stomach  ulcers in some people taking pain medicines called non-steroidal anti-inflammatory drugs (NSAIDs).

· for reducing the risk of stomach ulcers in some people taking NSAIDs.

· for up to 8 weeks for the relief of heartburn and other symptoms of gastroesophageal reflux disease (GERD).

GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour taste or burping.

· for 8 weeks to heal the acid-related damage to the lining of the esophagus (called erosive esophagitis) and to relieve symptoms. If needed, your doctor may prescribe another 8 weeks of lansoprazole delayed-release capsules.

· for continued healing of erosive esophagitis.

· for the long-term treatment of conditions where your stomach makes too much acid. This includes a condition called Zollinger-Ellison syndrome.

Lansoprazole delayed-release capsules are used in children and adolescents (ages 1 to 17):

· for up to 12 weeks to treat GERD and erosive esophagitis in children 1 to 11 years old.

·for up to 8 weeks to treat GERD and erosive esophagitis in adolescents 12 to17 years old.

Lansoprazole delayed-release capsules are not effective for symptoms of GERD in children under the age of 1 year.

Who should not take lansoprazole delayed-release capsules?

· Do not take lansoprazole delayed-release capsules if you are allergic to lansoprazole or any of the other ingredients in lansoprazole delayed-release capsules. See the end of this Medication Guide for a complete list of ingredients in lansoprazole delayed-release capsules.

What should I tell my doctor before taking lansoprazole delayed-release capsules?

Before you take lansoprazole delayed-release capsules, tell your doctor if you:

· have been told that you have low magnesium levels in your blood.

· have liver problems

· have any other medical conditions

·are pregnant or plan to become pregnant. It is not known if lansoprazole delayed-release capsules will harm your unborn baby.

· are breastfeeding or plan to breastfeed. It is not known if lansoprazole delayed-release capsules passes into your breast milk. You and your doctor should decide if you will take lansoprazole delayed-release capsulesor breastfeed. You should not do both. Talk to your doctor about the best way to feed your baby if you take lansoprazole delayed-release capsules.

Tell your doctor about all the medicines you take,including prescription and non-prescription medicines, vitamins, and herbal supplements. Lansoprazole delayed-release capsules may affect how other medicines work, and other medicines may affect how lansoprazole delayed-release capsules works.

Especially tell your doctor if you take:

· atazanavir (Reyataz)

· digoxin (Lanoxin)

· a product that contains iron

· ketoconazole (Nizoral)

· warfarin (Coumadin, Jantoven)

· tacrolimus (Prograf)

· theophylline (Theo-24, Elixophyllin, Theochron, Theolair)

· an antibiotic that contains ampicillin or clarithromycin

· methotrexate

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Know the medicines that you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take lansoprazole delayed-release capsules?

· Take lansoprazole delayed-release capsules exactly as prescribed by your doctor.

· Do not change your dose or stop taking lansoprazole delayed-release capsules without talking to your doctor.

· You should take lansoprazole delayed-release capsules before eating.

· Lansoprazole delayed-release capsules:

o   You shouldswallow lansoprazole delayed-release capsules whole.

o   Do not crush or chew lansoprazole delayed-release capsules.

o   If you have trouble swallowing a whole capsule, you can open the capsule and take the contents with certain foods or juices. See the “Instructions for Use” at the end of this Medication Guide for instructions on how to take lansoprazole delayed-release capsules with certain foods and juices.

o   See the “Instructions for Use” at the end of this Medication Guide for instructions on how to mix and give lansoprazole delayed-release capsules through a nasogastric tube.

·  If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Just take the next dose at your regular time. Do not take 2 doses at the same time.

· If you take too much lansoprazole delayed-release capsules, call your doctor right away.

What are the possible side effects of lansoprazole delayed-release capsules?

Lansoprazole delayed-release capsules can cause serious side effects, including:

·         See “What is the most important information that I should know about lansoprazole delayed-release capsules ?”

·         Low magnesium levels in your body. This problem can be serious. Low magnesium can happen  in some people who take a proton pump inhibitor medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment. You may or may not have symptoms of low magnesium.

Tell your doctor right away if you develop any of these symptoms:

·         seizures

·         dizziness

·         abnormal or fast heartbeat

·         jitteriness

·         jerking movements or shaking (tremors)

·         muscle weakness

·         spasms of the hands and feet

·         cramps or muscle aches

·         spasm of the voice box

Your doctor may check the level of magnesium in your body before you start taking lansoprazole delayed-release capsules, or during treatment; if you will be taking lansoprazole delayed-release capsulesfor a long period of time.

The most common side effects of lansoprazole delayed-release capsules in adults and children include:

· diarrhea

· stomach pain

· nausea

· constipation

· headache                                                                      

 Other side effects:

· Serious allergic reactions.Tell your doctor if you get any of the following symptoms with lansoprazole delayed-release capsules.

·   rash

·   face swelling

·   throat tightness

·   difficulty breathing

Your doctor may stop lansoprazole delayed-release capsules if these symptoms happen.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of lansoprazole delayed-release capsules. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How should I store lansoprazole delayed-release capsule?

· Store lansoprazole delayed-release capsules at room temperature between 68°F to 77°F (20°C to 25°C).

Keep lansoprazole delayed-release capsules and all medicines out of the reach of children.

General information about lansoprazole delayed-release capsules

Medicines are sometimes prescribed for conditions other than those listed in a Medication Guide. Do not use lansoprazole delayed-release capsules for conditions for which it was not prescribed. Do not give lansoprazole delayed-release capsules to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about lansoprazole delayed-release capsules. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about lansoprazole delayed-release capsules that is written for healthcare professionals.

For more information, call 1-800-367-3395 or go to www.bpirx.com.

What are ingredients in lansoprazole delayed-release capsules?

Active ingredient:lansoprazole.

Inactive ingredients in lansoprazole delayed-release capsules:

Acetone, hypromellose, isopropyl alcohol, light magnesium carbonate, methacrylic acid copolymer, polyethylene glycol, polysorbate 80, sugar spheres, talc and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

NATCO PHARMA LIMITED,

Kothur- 509228,

AP, India.

Distributed by:

Breckenridge Pharmaceutical, Inc.,

Boca Raton, FL 33487.

Lansoprazole delayed-release capsules

·         Swallow lansoprazole delayed-release capsules whole. Do not crush or chew them.

·         You should take lansoprazole delayed-release capsules before eating

·         Lansoprazole delayed-release capsules with certain food:

You can only use applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.

1        Open the capsule.

2        Sprinkle the granules on 1 tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.

3        Swallow right away.

·         Lansoprazole delayed-release capsules with certain juices:

You can only use apple juice, orange juice or tomato juice.

1        Open the capsule.

2        Sprinkle the granules into 60 mL (about ¼ cup) of either apple juice, orange juice or tomato juice.

3        Stir.

4        Swallow right away.

5        To make sure that the entire dose is taken, rinse the glass with 1/2 cup or more of juice to get out any leftover granules. Swallow the juice right away.

Lansoprazole delayed-release capsules through a nasogastric tube (NG tube) 16 French or larger, as prescribed by your doctor:

You can only use apple juice.

1        Open the capsule and empty the granules into a syringe.

2        Do not break or crush the granules.

3        Mix with 40 mL of apple juice. Do not use other liquids.

4        Attach the syringe to the NG tube and give the medicine in the syringe through the NG tube into the stomach.

5        After giving the granules, flush the NG tube with more apple juice to clear the tube.

Lansoprazole delayed-release capsules should not be used in foods or liquids not listed above.

How should I store lansoprazole delayed-release capsule?

·         Store lansoprazole delayed-release capsules at room temperature between 68°F to 77°F (20°C to 25°C).

Keep lansoprazole delayed-release capsules and all medicines out of the reach of children.

This Instruction for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:
NATCO PHARMA LIMITED,
Kothur-509 228,

AP, India.

Distributed by:

Breckenridge Pharmaceutical, Inc.,

Boca Raton, FL 33487.

Lansoprazole Delayed Release Capsules 15 mg-Bottle of 30 Capsules

NDC: 51991-771-33

Each green and pink colored capsule contains 15 mg of lansoprazole USP as enteric-coated pellets.

Each capsule is printed with NATCO and 15 for product identification.

Store at 25°C (77°F); excursions permitted to15-30°C (59-86°F) [See USP Controlled Room Temperature].

Do not accept if seal over bottle opening is broken or missing.

Lansoprazole Delayed Release Capsules 30 mg-Bottle of 30 Capsules

NDC: 51991-772-33

Each dark blue and pink colored capsule contains 30 mg of lansoprazole USP as enteric-coated pellets.

Each capsule is printed with NATCO and 30 for product identification.

Store at 25°C (77°F); excursions permitted to15-30°C (59-86°F) [See USP Controlled Room Temperature].

Do not accept if seal over bottle opening is broken or missing.

 Container label:

Lansoprazole Delayed Release Capsules 30 mg-Bottle of 90 Capsules

NDC: 51991-772-90

Each dark blue and pink colored capsule contains 30 mg of lansoprazole USP as enteric-coated pellets.

Each capsule is printed with NATCO and 30 for product identification.

Store at 25°C (77°F); excursions permitted to15-30°C (59-86°F) [See USP Controlled Room Temperature].

Do not accept if seal over bottle opening is broken or missing.

Lansoprazole Delayed Release Capsules 30 mg-Bottle of 500 Capsules

NDC: 51991-772-05

Each dark blue and pink colored capsule contains 30 mg of lansoprazole USP as enteric-coated pellets.

Each capsule is printed with NATCO and 30 for product identification.

Store at 25°C (77°F); excursions permitted to15-30°C (59-86°F) [See USP Controlled Room Temperature].

Do not accept if seal over bottle opening is broken or missing.

 Container label: