1 INDICATIONS AND USAGE Lansoprazole delayed-release capsules is a proton pump inhibitor (PPI) indicated for the: Treatment of active duodenal ulcer in adults.

( 1.1 ) Eradication of H.

pylori to reduce the risk of duodenal ulcer recurrence in adults.

( 1.2 ) Maintenance of healed duodenal ulcers in adults.

( 1.3 ) Treatment of active benign gastric ulcer in adults.

( 1.4 ) Healing of nonsteroidal anti-inflammatory drugs (NSAID)-associated gastric ulcer in adults.

( 1.5 ) Risk reduction of NSAID-associated gastric ulcer in adults.

( 1.6 ) Treatment of symptomatic gastroesophageal reflux disease (GERD) in adults and pediatric patients 1 year of age and older.

( 1.7 ) Treatment of erosive esophagitis (EE) in adults and pediatric patients 1 year of age and older.

( 1.8 ) Maintenance of healing of EE in adults.

( 1.9 ) Pathological hypersecretory conditions, including Zollinger-Ellison syndrome (ZES) in adults.

( 1.10 ) 1.1 Treatment of Active Duodenal Ulcer Lansoprazole delayed-release capsules are indicated in adults for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [ see Clinical Studies ( 14.1 ) ].

1.2 Eradication of H.

pylori to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: Lansoprazole delayed-release capsules/amoxicillin/clarithromycin Lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated in adults for the treatment of patients with H.

pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) to eradicate H.

pylori .

Eradication of H.

pylori has been shown to reduce the risk of duodenal ulcer recurrence [ see Clinical Studies ( 14.2 ) ].

Please refer to the full prescribing information for amoxicillin and clarithromycin.

Dual Therapy: Lansoprazole delayed-release capsules/ amoxicillin Lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated in adults for the treatment of patients with H.

pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, Microbiology section).

Eradication of H.

pylori has been shown to reduce the risk of duodenal ulcer recurrence [ see Clinical Studies ( 14.2 ) ].

Please refer to the full prescribing information for amoxicillin.

1.3 Maintenance of Healed Duodenal Ulcers Lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers.

Controlled studies do not extend beyond 12 months [ see Clinical Studies ( 14.3 ) ].

1.4 Treatment of Active Benign Gastric Ulcer Lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [ see Clinical Studies ( 14.4 ) ].

1.5 Healing of NSAID-Associated Gastric Ulcer Lansoprazole delayed-release capsules are indicated in adults for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use.

Controlled studies did not extend beyond eight weeks [ see Clinical Studies ( 14.5 ) ].

1.6 Risk Reduction of NSAID-Associated Gastric Ulcer Lansoprazole delayed-release capsules are indicated in adults 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 ( 14.6 ) ].

1.8 Treatment of Erosive Esophagitis (EE) Lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of EE.

For adults who do not heal with lansoprazole delayed-release capsules for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment.

If there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole delayed-release capsules may be considered [ see Clinical Studies ( 14.8 )].

1.7 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) Lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with GERD [see Clinical Studies ( 14.7 )].

1.9 Maintenance of Healing of EE Lansoprazole delayed-release capsules are indicated in adults to maintain healing of EE.

Controlled studies did not extend beyond 12 months [ see Clinical Studies ( 14.9 ) ].

1.10 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome (ZES) Lansoprazole delayed-release capsules, USP are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome [ see Clinical Studies ( 14.10 ) ].

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions ( 5.2 )] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.3)] Bone Fracture [see Warnings and Precautions ( 5.4 )] Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5 )] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions ( 5.6 )] Cyanocobalamin (Vitamin B12) Deficiency [see Warnings and Precautions ( 5.7 )] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions ( 5.8 )] Fundic Gland Polyps [see Warnings and Precautions ( 5.12 )] Most commonly reported adverse reactions (≥ 1%): diarrhea, abdominal pain, nausea and constipation.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact at Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience 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.

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.

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 Reaction Lansoprazole (N= 2768) % Placebo (N= 1023) % Body as a Whole Abdominal Pain 2.1 1.2 Digestive System Constipation 1.0 0.4 Diarrhea 3.8 2.3 Nausea 1.3 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 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 Metabolism 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 has been marketed.

The majority of these cases are foreign- sourced and a relationship to lansoprazole delayed-release capsules 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.

Body as a Whole – anaphylactic/anaphylactoid reactions, systemic lupus erythematosus; Digestive System – hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System – agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Infections and Infestations - Clostridium difficile -associated diarrhea; Metabolism and Nutritional Disorders – hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia; Musculoskeletal System – bone fracture, myositis; Skin and Appendages – severe dermatologic reactions including erythema multiforme, SJS/TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus; 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.

Triple Therapy: Lansoprazole/amoxicillin/clarithromycin 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: Lansoprazole/amoxicillin The most frequently reported adverse reactions for patients who received 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 lansoprazole three times daily plus amoxicillin three times daily dual therapy than with lansoprazole alone.

For information about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with lansoprazole delayed-release capsules, refer to the Adverse Reactions section of their prescribing information.

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 about laboratory value changes with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with lansoprazole delayed-release capsules, refer to the Adverse Reactions section of their prescribing information.