FDA Label for Lansoprazole

View Indications, Usage & Precautions

1.1 SHORT-TERM TREATMENT OF ACTIVE DUODENAL ULCER
1.3 MAINTENANCE OF HEALED DUODENAL ULCERS
1.4 SHORT-TERM TREATMENT OF ACTIVE BENIGN GASTRIC ULCER
1.5 HEALING OF NSAID-ASSOCIATED GASTRIC ULCER
1.6 RISK REDUCTION OF NSAID-ASSOCIATED GASTRIC ULCER
1.8 MAINTENANCE OF HEALING OF EROSIVE ESOPHAGITIS (EE)
1.9 PATHOLOGICAL HYPERSECRETORY CONDITIONS INCLUDING ZOLLINGER-ELLISON SYNDROME (ZES)
2 DOSAGE AND ADMINISTRATION
2.1 RECOMMENDED DOSE
2.2 SPECIAL POPULATIONS
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5.1 GASTRIC MALIGNANCY
5.2 BONE FRACTURE
6.1 CLINICAL
6.2 POSTMARKETING EXPERIENCE
6.3 COMBINATION THERAPY WITH AMOXICILLIN AND CLARITHROMYCIN
6.4 LABORATORY VALUES
8.3 NURSING MOTHERS
8.4 PEDIATRIC USE
8.5 GERIATRIC USE
8.6 RENAL IMPAIRMENT
8.7 HEPATIC IMPAIRMENT
8.8 GENDER
8.9 RACE
10 OVERDOSAGE
11 DESCRIPTION
12.1 MECHANISM OF ACTION
12.3 PHARMACOKINETICS
12.5 DRUG-DRUG INTERACTIONS
13.1 CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
OTHER
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
SPL PATIENT PACKAGE INSERT
PACKAGE LABEL - LANSOPRAZOLE D/R 15 MG CAPSULES
PACKAGE LABEL - LANSOPRAZOLE D/R 30 MG CAPSULES

Lansoprazole Product Label

The following document was submitted to the FDA by the labeler of this product Stat Rx Usa Llc. The document includes published materials associated whith this product with the essential scientific information about this product as well as other prescribing information. Product labels may durg indications and usage, generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, warnings, inactive ingredients, etc.

1.1 Short-Term Treatment Of Active Duodenal Ulcer

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated for short-term treatment (for 4 weeks) for healing and symptom relief of active duodenal ulcer [see Clinical Studies (14)].

1.3 Maintenance Of Healed Duodenal Ulcers

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months [see Clinical Studies (14)].

1.4 Short-Term Treatment Of Active Benign Gastric Ulcer

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated for short-term treatment (up to 8 weeks) for healing and symptom relief of active benign gastric ulcer [see Clinical Studies (14)].

1.5 Healing Of Nsaid-Associated Gastric Ulcer

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled studies did not extend beyond 8 weeks [see Clinical Studies (14)].

1.6 Risk Reduction Of Nsaid-Associated Gastric Ulcer

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated for reducing the risk of NSAID-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an NSAID. Controlled studies did not extend beyond 12 weeks [see Clinical Studies (14)].

1.8 Maintenance Of Healing Of Erosive Esophagitis (Ee)

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated to maintain healing of erosive esophagitis. Controlled studies did not extend beyond 12 months [see Clinical Studies (14)].

1.9 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome (Zes)

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome [see Clinical Studies (14)].

2 Dosage And Administration

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets 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 are presented below. Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets should be taken before eating. Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets SHOULD NOT BE CRUSHED OR CHEWED. In the clinical trials, antacids were used concomitantly with lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets.

2.1 Recommended Dose

Indication	Recommended Dose	Frequency
Duodenal Ulcers
Short-Term Treatment	15 mg	Once daily for 4 weeks
Maintenance of Healed	15 mg	Once daily
H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Please refer to amoxicillin and clarithromycin full prescribing information for CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly and renally-impaired patients.
Triple Therapy:
Lansoprazole	30 mg	Twice daily (q12h) for 10 or 14 days
Amoxicillin	1 gram	Twice daily (q12h) for 10 or 14 days
Clarithromycin	500 mg	Twice daily (q12h) for 10 or 14 days
Dual Therapy:
Lansoprazole	30 mg	Three times daily (q8h) for 14 days
Amoxicillin	1 gram	Three times daily (q8h) for 14 days
Benign Gastric Ulcer Short-Term Treatment	30 mg	Once daily for up to 8 weeks
NSAID-associated Gastric Ulcer Healing Risk Reduction	30 mg 15 mg	Once daily for 8 weeks Controlled studies did not extend beyond indicated duration. Once daily for up to 12 weeks
Gastroesophageal Reflux Disease (GERD)
Short-Term Treatment of Symptomatic GERD	15 mg	Once daily for up to 8 weeks
Short-Term Treatment of Erosive Esophagitis	30 mg	Once daily for up to 8 weeks For patients who do not heal with lansoprazole for 8 weeks (5 to 10%), it may be helpful to give an additional 8 weeks of treatment. If there is a recurrence of erosive esophagitis, an additional 8 week course of lansoprazole may be considered.
Pediatric
(1 to 11 years of age) Short-Term Treatment of Symptomatic GERD and Short-Term Treatment of Erosive Esophagitis
≤ 30 kg	15 mg	Once daily for up to 12 weeks The lansoprazole dose was increased (up to 30 mg twice daily) in some pediatric patients after 2 or more weeks of treatment if they remained symptomatic. For pediatric patients unable to swallow an intact capsule please see Administration Options.
> 30 kg	30 mg	Once daily for up to 12 weeks
(12 to 17 years of age) Short-Term Treatment of Symptomatic GERD
Nonerosive GERD	15 mg	Once daily for up to 8 weeks
Erosive Esophagitis	30 mg	Once daily for up to 8 weeks
Maintenance of Healing of Erosive Esophagitis	15 mg	Once daily
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome	60 mg	Once daily Varies with individual patient. Recommended adult starting dose is 60 mg once daily. Doses should be adjusted to individual patient needs and should continue for as long as clinically indicated. Dosages up to 90 mg twice daily have been administered. Daily dose of greater than 120 mg should be administered in divided doses. Some patients with Zollinger-Ellison Syndrome have been treated continuously with lansoprazole for more than 4 years.

2.2 Special Populations

Renal impairment patients and geriatric patients do not require dosage adjustment. However, consider dose adjustment in patients with severe liver impairment [see Use in Specific Populations (8.5 , 8.6 and 8.7)].

3 Dosage Forms And Strengths

15 mg capsules are opaque, hard gelatin, colored pink and green with the TAP logo and "PREVACID 15" imprinted on the capsule.
30 mg capsules are opaque, hard gelatin, colored pink and black with the TAP logo and "PREVACID 30" imprinted on the capsule.
15 mg tablets are white to yellowish white, uncoated, colored orange to dark brown speckles with "15" debossed on one side of the tablet.
30 mg tablets are white to yellowish white, uncoated, colored orange to dark brown speckles with "30" debossed on one side of the tablet.

4 Contraindications

Lansoprazole is contraindicated in patients with known severe hypersensitivity to any component of the formulation of lansoprazole.

For information on contraindications for amoxicillin or clarithromycin, refer to their full prescribing information, CONTRAINDICATIONS sections.

5.1 Gastric Malignancy

Symptomatic response to therapy with lansoprazole does not preclude the presence of gastric malignancy.

5.2 Bone Fracture

Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) and Adverse Reactions (6.2)].

For information on warnings and precautions for amoxicillin or clarithromycin, refer to their full prescribing information, WARNINGS and PRECAUTIONS sections.

6.1 Clinical

Worldwide, over 10,000 patients have been treated with lansoprazole in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, lansoprazole treatment has been well-tolerated in both short-term and long-term trials.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The following adverse reactions were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of lansoprazole-treated patients and occurred at a greater rate in lansoprazole-treated patients than placebo-treated patients in Table 1.

Table 1: Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled Lansoprazole Studies
Body System/Adverse Event	Lansoprazole (N= 2768) %	Placebo (N= 1023) %
Body as a Whole Abdominal Pain	2.1	1.2
Digestive System Constipation Diarrhea Nausea	1.0 3.8 1.3	0.4 2.3 1.2

Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhea was similar between patients who received placebo and patients who received 15 mg and 30 mg of lansoprazole, but higher in the patients who received 60 mg of lansoprazole (2.9%, 1.4%, 4.2%, and 7.4%, respectively).

The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea.

In the risk reduction study of lansoprazole for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with lansoprazole, misoprostol, and placebo was 5%, 22%, and 3%, respectively.

Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with lansoprazole included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment.

Additional adverse experiences occurring in less than 1% of patients or subjects who received lansoprazole in domestic trials are shown below:

Body as a Whole – abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain

Cardiovascular System – angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation

Digestive System – abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation, melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis

Endocrine System – diabetes mellitus, goiter, hypothyroidism

Hemic and Lymphatic System – anemia, hemolysis, lymphadenopathy

Metabolic and Nutritional Disorders – avitaminosis, gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss

Musculoskeletal System – arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis

Nervous System – abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo

Respiratory System – asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor

Skin and Appendages – acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria

Special Senses – abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste perversion, tinnitus, visual field defect

Urogenital System – abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency, urination impaired, vaginitis.

6.2 Postmarketing Experience

Additional adverse experiences have been reported since lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets have been marketed. The majority of these cases are foreign-sourced and a relationship to lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets have 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.

Body as a Whole – anaphylactic/anaphylactoid reactions; Digestive System - hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Musculoskeletal System – bone fracture, myositis; Skin and Appendages – severe dermatologic reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal); Special Senses - speech disorder; Urogenital System – interstitial nephritis, urinary retention.

6.3 Combination Therapy With Amoxicillin And Clarithromycin

In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with lansoprazole, amoxicillin, or clarithromycin.

6.4 Laboratory Values

The following changes in laboratory parameters in patients who received lansoprazole were reported as adverse reactions:

Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported.

In the placebo controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who received placebo and 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 lansoprazole reported jaundice at any time during the study.

In clinical trials using combination therapy with lansoprazole plus amoxicillin and clarithromycin, and lansoprazole plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed.

For information on laboratory value changes with amoxicillin or clarithromycin, refer to their full prescribing information, ADVERSE REACTIONS sections.

8.3 Nursing Mothers

Lansoprazole or its metabolites are excreted in the milk of rats. It is not known whether lansoprazole is excreted in human milk. Because many drugs are excreted in human milk, because of the potential for serious adverse reactions in nursing infants from lansoprazole, and because of the potential for tumorigenicity shown for lansoprazole in rat carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue lansoprazole, taking into account the importance of lansoprazole to the mother.

8.4 Pediatric Use

The safety and effectiveness of lansoprazole have been established in pediatric patients 1 to 17 years of age for short-term treatment of symptomatic GERD and erosive esophagitis, however, lansoprazole was not effective in patients with symptomatic GERD 1 month to less than 1 year of age in a multicenter, double-blind, placebo controlled study.

8.5 Geriatric Use

No dosage adjustment of lansoprazole is necessary in geriatric patients. The incidence rates of lansoprazole-associated adverse reactions and laboratory test abnormalities are similar to those seen in younger patients [see Clinical Pharmacology (12.4)].

8.6 Renal Impairment

No dosage adjustment of lansoprazole is necessary in patients with renal impairment. The pharmacokinetics of lansoprazole in patients with various degrees of renal impairment were not substantially different compared to those in subjects with normal renal function [see Clinical Pharmacology (12.4)].

8.7 Hepatic Impairment

In patients with various degrees of chronic hepatic impairment, an increase in the mean AUC of up to 500% was observed at steady state compared to healthy subjects. Consider dose reduction in patients with severe hepatic impairment [see Clinical Pharmacology (12.4)].

8.8 Gender

Over 4,000 women were treated with lansoprazole. Ulcer healing rates in females were similar to those in males. The incidence rates of adverse reactions in females were similar to those seen in males [see Clinical Pharmacology (12.4)].

8.9 Race

The pooled mean pharmacokinetic parameters of lansoprazole from twelve U.S. Phase 1 studies (N=513) were compared to the mean pharmacokinetic parameters from two Asian studies (N=20). The mean AUCs of lansoprazole in Asian subjects were approximately twice those seen in pooled U.S. data; however, the inter-individual variability was high. The C_max values were comparable.

10 Overdosage

Lansoprazole is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of lansoprazole with no adverse reaction. Oral lansoprazole doses up to 5000 mg/kg in rats [approximately 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.

11 Description

The active ingredient in Lansoprazole Delayed-Release Capsules and Lansoprazole 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 C₁₆H₁₄F₃N₃O₂S with a molecular weight of 369.37. Lansoprazole has the following structure:

Chemical Structure - lansoprazole 01

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 capsules and in delayed-release orally disintegrating tablets for oral administration.

Lansoprazole 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

Lansoprazole 15-mg capsules only.

, and FD&C Red No. 40.

Lansoprazole 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

Phenylketonurics: Contains Phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg Tablet.

, glyceryl monostearate, hypromellose, magnesium stearate, citric acid, titanium dioxide, talc, artificial strawberry flavor, polyethylene glycol, polysorbate 80 and ferric oxide.

12.1 Mechanism Of Action

Lansoprazole 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.

12.3 Pharmacokinetics

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets 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.

12.5 Drug-Drug Interactions

It is theoretically possible that lansoprazole may interfere with the absorption of other drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, ampicillin esters, iron salts, digoxin).

Lansoprazole is metabolized through the cytochrome P₄₅₀ system, specifically through the CYP3A and CYP2C19 isozymes. Studies have shown that lansoprazole does not have clinically significant interactions with other drugs metabolized by the cytochrome P₄₅₀ system, such as warfarin, antipyrine, indomethacin, ibuprofen, phenytoin, propranolol, prednisone, diazepam, or clarithromycin in healthy subjects. These compounds are metabolized through various cytochrome P₄₅₀ isozymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A.

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.

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 ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, the in vivo mouse micronucleus test, or the rat bone marrow cell chromosomal aberration test. It was positive in in vitro human lymphocyte chromosomal aberration assays.

Lansoprazole at oral doses up to 150 mg/kg/day (40 times the recommended human dose based on BSA) was found to have no effect on fertility and reproductive performance of male and female rats.

Other

Long-Term Maintenance Treatment of Erosive Esophagitis

Two independent, double-blind, multicenter, controlled trials were conducted in patients with endoscopically confirmed healed esophagitis. Patients remained in remission significantly longer and the number of recurrences of erosive esophagitis was significantly less in patients treated with lansoprazole than in patients treated with placebo over a 12-month period (Table 21).

Table 21: Endoscopic Remission Rates
			Percent in Endoscopic Remission
Trial	Drug	No. of Pts.	0-3 mo.	0-6 mo.	0-12 mo.
%=Life Table Estimate
#1	Lansoprazole 15 mg daily	59	83% (p≤0.001) versus placebo.	81%	79%
	Lansoprazole 30 mg daily	56	93%	93%	90%
	Placebo	55	31%	27%	24%
#2	Lansoprazole 15 mg daily	50	74%	72%	67%
	Lansoprazole 30 mg daily	49	75%	72%	55%
	Placebo	47	16%	13%	13%

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

In a U.S., randomized, double-blind, study, lansoprazole 15 mg daily (n = 100) was compared with ranitidine 150 mg twice daily (n = 106), at the recommended dosage, in patients with endoscopically-proven healed erosive esophagitis over a 12-month period. Treatment with lansoprazole resulted in patients remaining healed (Grade 0 lesions) of erosive esophagitis for significantly longer periods of time than those treated with ranitidine (p<0.001). In addition, lansoprazole was significantly more effective than ranitidine in providing complete relief of both daytime and nighttime heartburn. Patients treated with lansoprazole remained asymptomatic for a significantly longer period of time than patients treated with ranitidine [see Indications and Usage (1.8)].

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, 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 [see Dosage and Administration (2.1)]. 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 lansoprazole. 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)].

Information for Patients

Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets should be taken before eating.
Lansoprazole delayed-release capsules and lansoprazole delayed-release orally disintegrating tablets SHOULD NOT BE CRUSHED OR CHEWED.
Phenylketonurics: Contains Phenylalanine 2.5 mg per 15 mg Tablet and 5.1 mg per 30 mg Tablet.

Administration Options

1Lansoprazole 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:
  - Open capsule.
  - Sprinkle intact granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
  - 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:
    - Open capsule.
    - Sprinkle intact granules into a small volume of either apple juice, orange juice or tomato juice (60 mL – approximately 2 ounces).
    - Mix briefly.
    - Swallow immediately.
    - To ensure complete delivery of the dose, the glass should be rinsed with two or more volumes of juice and the contents swallowed immediately.

15 References

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, are opaque, hard gelatin, colored pink and green with "TAP" and "PREVACID 15" imprinted on the capsules. The 30 mg capsules are opaque, hard gelatin, colored pink and black with "TAP" and "PREVACID 30" imprinted on the capsules. They are available as follows:

NDC 0781-2353-31	Bottles of 30: 15-mg capsules
NDC 0781-2353-10	Bottles of 1000: 15-mg capsules
NDC 0781-2355-01	Bottles of 100: 30-mg capsules
NDC 0781-2355-10	Bottles of 1000: 30-mg capsules

Lansoprazole 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:

NDC 0781-5733-13	Unit dose packages of 100: 15-mg tablets
NDC 0781-5734-13	Unit dose packages of 100: 30-mg tablets

Storage And Handling

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

17 Patient Counseling Information

Patient should be informed of the following:

Spl Patient Package Insert

Patient Information

Lansoprazole
Delayed-Release Capsules
and
Lansoprazole
Delayed-Release Orally Disintegrating Tablets

Read the information that comes with Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets?

Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets is a prescription medicine called a proton pump inhibitor (PPI). Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets reduces the amount of acid in your stomach.

Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets is used in adults:

for 4 weeks to heal ulcers in the first part of the small bowel (duodenal ulcers).
for up to 12 months to stop healed duodenal ulcers from coming back.
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 reducing the risk of stomach infections (Helicobacter pylori), along with antibiotics amoxicillin and clarithromycin.
for up to 8 weeks for the relief of heartburn and other symptoms of gastroesophageal reflux disease (GERD).

GERD happens when acid from your stomach enters 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. In some cases, acid can damage the lining of your esophagus. This damage is called erosive esophagitis.
for 8 weeks to heal the acid-related damage to the lining of the esophagus (called erosive esophagitis) and to relieve symptoms, such as heartburn pain. If needed, your doctor may prescribe an additional 8 weeks of Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets
to stop erosive esophagitis from coming back (studies lasted 12 months).
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 or Lansoprazole Delayed-Release Orally Disintegrating Tablets is used in children and adolescents (ages 1-17):

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 to 17 years old.

Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets is not recommended for children under the age of 1 year.

Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

Who should not take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets?

Do not take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets if you are allergic to Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets or any of its ingredients. See the end of this leaflet for a complete list of ingredients in Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets.

What should I tell my doctor before taking Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets?

Before you take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets, tell your doctor if you:

have liver problems
have phenylketonuria. Lansoprazole Delayed-Release Orally Disintegrating Tablets contains aspartame.
have any other medical conditions
are pregnant or plan to become pregnant. It is not known if Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
are breast-feeding or planning to breast-feed. You and your doctor should decide if you will take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets or breast-feed. You should not do both without first talking with your doctor.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets may affect how other medicines work, or other medicines may affect how Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets works. Especially tell your doctor if you take:

ampicillin sodium (Unasyn) or ampicillin trihydrate (Principen)
atazanavir (Reyataz)
digoxin (Lanoxicaps, Lanoxin)
a product that contains iron
ketoconazole (Nizoral)
warfarin (Coumadin, Jantoven)
tacrolimus (Prograf)
theophylline (Theo-24, Theolair)

Ask your doctor or pharmacist if you are not sure if your medicine is listed above.

How should I take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets?

Take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets exactly as prescribed by your doctor.
Do not change your dose or stop taking Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets without talking to your doctor first.
You should take Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets before eating.
Lansoprazole Delayed-Release Capsules can be swallowed whole, do not crush or chew them. They can also be opened and sprinkled into approximately ¼ cup apple, tomato or orange juice, or on 1 tablespoon applesauce, Ensure pudding, cottage cheese, yogurt or strained pears only. See "Patient Instructions for Use" at the end of this leaflet for instructions on how to take Lansoprazole Delayed-Release Capsules with these foods, and how to mix and give Lansoprazole Delayed-Release Capsules through a nasogastric tube.
Lansoprazole Delayed-Release Orally Disintegrating Tablets is a tablet that melts in your mouth with or without water. Do not break, cut or chew the tablets. See "Patient Instructions for Use" at the end of this leaflet for instructions on how to mix and give Lansoprazole Delayed-Release Orally Disintegrating Tablets through a syringe and 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 are not sure about dosing, call your doctor.
If you take too much Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets, call your doctor right away.

What are the possible side effects of Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets?

Serious allergic reactions. Tell your doctor if you get any of the following symptoms with Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets

rash
face swelling
throat tightness
difficulty breathing

Your doctor may stop Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets if these symptoms happen.

The most common side effects of Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets in adults and children include:

diarrhea
stomach pain
nausea
constipation
headache
dizziness

People who are taking multiple daily doses of proton pump inhibitor medicines for a long period of time may have an increased risk of fractures of the hip, wrist or spine.

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 or Lansoprazole Delayed-Release Orally Disintegrating Tablets. 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 Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets?

Store Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets at room temperature between 59° to 86°F (15° to 30°C).

Keep Lansoprazole Delayed-Release Capsules and Lansoprazole Delayed-Release Orally Disintegrating Tablets and all medicines out of the reach of children.

General information about Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets

Medicines are sometimes prescribed for conditions other than those listed in a Patient Information Leaflet. Do not use Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets for conditions for which it was not prescribed. Do not give Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information Leaflet provides a summary of the most important information about Lansoprazole Delayed-Release Capsules or Lansoprazole Delayed-Release Orally Disintegrating Tablets. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals. For more information, call 1-877-825-3327.

Patient Instructions for Use

Lansoprazole Delayed-Release Capsules

Swallow Lansoprazole Delayed-Release Capsules whole. Do not crush or chew them.
If you have trouble swallowing a whole capsule, you can open the capsule and take it with the foods or juices listed below.

For taking Lansoprazole Delayed-Release Capsules with applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears:
- Open the capsule.
- Sprinkle the granules on one tablespoon of either applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears.
- Swallow right away.

Package Label - Lansoprazole D/R 15 Mg Capsules

Package Label - Lansoprazole D/R 30 Mg Capsules

* Please review the disclaimer below.

Table of Contents