FDA label f517d5f1-7d2e-4231-822d-e28898925664

Figure 1: Mean Plasma Dexlansoprazole Concentration – Time Profile Following Oral Administration of 30 or 60 mg DEXILANT Once Daily for 5 Days in Healthy Subjects

5 WARNINGS AND PRECAUTIONS Gastric malignancy : Symptomatic response with DEXILANT does not preclude the presence of gastric malignancy. ( 5.1 ) Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.2 ) Hypomagnesemia : Hypomagnesemia has been reported rarely with prolonged treatment with PPIs. ( 5.3 ) 5.1 Gastric Malignancy Symptomatic response with DEXILANT 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) ]. 5.3 Hypomagnesemia Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2) ].

6 ADVERSE REACTIONS Most commonly reported adverse reactions (≥2%): diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) 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 practice. The safety of DEXILANT was evaluated in 4548 patients in controlled and uncontrolled clinical studies, including 863 patients treated for at least 6 months and 203 patients treated for one year. Patients ranged in age from 18 to 90 years (median age 48 years), with 54% female, 85% Caucasian, 8% Black, 4% Asian, and 3% other races. Six randomized controlled clinical trials were conducted for the treatment of EE, maintenance of healed EE, and symptomatic GERD, which included 896 patients on placebo, 455 patients on DEXILANT 30 mg, 2218 patients on DEXILANT 60 mg, and 1363 patients on lansoprazole 30 mg once daily. Most Commonly Reported Adverse Reactions The most common adverse reactions (≥2%) that occurred at a higher incidence for DEXILANT than placebo in the controlled studies are presented in Table 2. Table 2: Incidence of Adverse Reactions in Controlled Studies Placebo DEXILANT 30 mg DEXILANT 60 mg DEXILANT Total Lansoprazole 30 mg Adverse Reaction (N=896) % (N=455) % (N=2218) % (N=2621) % (N=1363) % Diarrhea 2.9 5.1 4.7 4.8 3.2 Abdominal Pain 3.5 3.5 4.0 4.0 2.6 Nausea 2.6 3.3 2.8 2.9 1.8 Upper Respiratory Tract Infection 0.8 2.9 1.7 1.9 0.8 Vomiting 0.8 2.2 1.4 1.6 1.1 Flatulence 0.6 2.6 1.4 1.6 1.2 Adverse Reactions Resulting in Discontinuation In controlled clinical studies, the most common adverse reaction leading to discontinuation from DEXILANT therapy was diarrhea (0.7%). Other Adverse Reactions Other adverse reactions that were reported in controlled studies at an incidence of less than 2% are listed below by body system: Blood and Lymphatic System Disorders: anemia, lymphadenopathy Cardiac Disorders: angina, arrhythmia, bradycardia, chest pain, edema, myocardial infarction, palpitation, tachycardia Ear and Labyrinth Disorders: ear pain, tinnitus, vertigo Endocrine Disorders: goiter Eye Disorders: eye irritation, eye swelling Gastrointestinal Disorders: abdominal discomfort, abdominal tenderness, abnormal feces, anal discomfort, Barrett's esophagus, bezoar, bowel sounds abnormal, breath odor, colitis microscopic, colonic polyp, constipation, dry mouth, duodenitis, dyspepsia, dysphagia, enteritis, eructation, esophagitis, gastric polyp, gastritis, gastroenteritis, gastrointestinal disorders, gastrointestinal hypermotility disorders, GERD, GI ulcers and perforation, hematemesis, hematochezia, hemorrhoids, impaired gastric emptying, irritable bowel syndrome, mucus stools, oral mucosal blistering, painful defecation, proctitis, paresthesia oral, rectal hemorrhage, retching General Disorders and Administration Site Conditions: adverse drug reaction, asthenia, chest pain, chills, feeling abnormal, inflammation, mucosal inflammation, nodule, pain, pyrexia Hepatobiliary Disorders: biliary colic, cholelithiasis, hepatomegaly Immune System Disorders: hypersensitivity Infections and Infestations: candida infections, influenza, nasopharyngitis, oral herpes, pharyngitis, sinusitis, viral infection, vulvo-vaginal infection Injury, Poisoning and Procedural Complications: falls, fractures, joint sprains, overdose, procedural pain, sunburn Laboratory Investigations: ALP increased, ALT increased, AST increased, bilirubin decreased/increased, blood creatinine increased, blood gastrin increased, blood glucose increased, blood potassium increased, liver function test abnormal, platelet count decreased, total protein increased, weight increase Metabolism and Nutrition Disorders: appetite changes, hypercalcemia, hypokalemia Musculoskeletal and Connective Tissue Disorders: arthralgia, arthritis, muscle cramps, musculoskeletal pain, myalgia Nervous System Disorders: altered taste, convulsion, dizziness, headaches, migraine, memory impairment, paresthesia, psychomotor hyperactivity, tremor, trigeminal neuralgia Psychiatric Disorders: abnormal dreams, anxiety, depression, insomnia, libido changes Renal and Urinary Disorders: dysuria, micturition urgency Reproductive System and Breast Disorders: dysmenorrhea, dyspareunia, menorrhagia, menstrual disorder Respiratory, Thoracic and Mediastinal Disorders: aspiration, asthma, bronchitis, cough, dyspnoea, hiccups, hyperventilation, respiratory tract congestion, sore throat Skin and Subcutaneous Tissue Disorders: acne, dermatitis, erythema, pruritis, rash, skin lesion, urticaria Vascular Disorders: deep vein thrombosis, hot flush, hypertension Additional adverse reactions that were reported in a long-term uncontrolled study and were considered related to DEXILANT by the treating physician included: anaphylaxis, auditory hallucination, B-cell lymphoma, bursitis, central obesity, cholecystitis acute, dehydration, diabetes mellitus, dysphonia, epistaxis, folliculitis, gout, herpes zoster, hyperlipidemia, hypothyroidism, increased neutrophils, MCHC decrease, neutropenia, rectal tenesmus, restless legs syndrome, somnolence, tonsillitis. Other adverse reactions not observed with DEXILANT, but occurring with the racemate lansoprazole can be found in the lansoprazole prescribing information, ADVERSE REACTIONS section. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval of DEXILANT. As these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura Ear and Labyrinth Disorders: deafness Eye Disorders: blurred vision Gastrointestinal Disorders: oral edema, pancreatitis General Disorders and Administration Site Conditions: facial edema Hepatobiliary Disorders: drug-induced hepatitis Immune System Disorders: anaphylactic shock (requiring emergency intervention), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal) Metabolism and Nutrition Disorders: hypomagnesemia, hyponatremia Musculoskeletal System Disorders: bone fracture Nervous System Disorders: cerebrovascular accident, transient ischemic attack Renal and Urinary Disorders: acute renal failure Respiratory, Thoracic and Mediastinal Disorders: pharyngeal edema, throat tightness Skin and Subcutaneous Tissue Disorders: generalized rash, leucocytoclastic vasculitis

<table ID="table2"> <caption ID="id_901c01d1-33dd-4e87-89a3-0836863f7fa6">Table 2: Incidence of Adverse Reactions in Controlled Studies</caption> <col width="33%" align="left"/> <col width="13%" align="center"/> <col width="13%" align="center"/> <col width="13%" align="center"/> <col width="13%" align="center"/> <col width="15%" align="center"/> <thead> <tr ID="id_073791f7-86fc-4308-b5c3-8d5a0ab86f59" styleCode="Toprule"> <td align="left" valign="top" styleCode="Botrule Rrule"/> <td align="left" valign="top" styleCode="Botrule Rrule">Placebo</td> <td align="left" valign="top" styleCode="Botrule Rrule">DEXILANT 30 mg</td> <td align="left" valign="top" styleCode="Botrule Rrule">DEXILANT 60 mg</td> <td align="left" valign="top" styleCode="Botrule Rrule">DEXILANT Total</td> <td align="left" valign="top" styleCode="Lrule Botrule">Lansoprazole 30 mg</td> </tr> <tr ID="id_1eb5e943-3bc1-4dbc-8cdc-a65cc2efc50f" styleCode="Botrule"> <td align="left" valign="top" styleCode="Rrule">Adverse Reaction</td> <td align="left" valign="top" styleCode="Rrule">(N=896) %</td> <td align="left" valign="top" styleCode="Rrule">(N=455) %</td> <td align="left" valign="top" styleCode="Rrule">(N=2218) %</td> <td align="left" valign="top" styleCode="Rrule">(N=2621) %</td> <td align="left" valign="top">(N=1363) %</td> </tr> </thead> <tbody> <tr ID="id_d5f3b2c6-d7dd-4c8c-bd81-a89ada3613f6" styleCode="Toprule"> <td align="left" valign="top" styleCode="Rrule">Diarrhea</td> <td align="left" valign="top" styleCode="Rrule">2.9</td> <td align="left" valign="top" styleCode="Rrule">5.1</td> <td align="left" valign="top" styleCode="Rrule">4.7</td> <td align="left" valign="top" styleCode="Rrule">4.8</td> <td align="left" valign="top">3.2</td> </tr> <tr ID="id_0d6f7c32-9bbd-4613-9554-68242599b86e"> <td align="left" valign="top" styleCode="Rrule">Abdominal Pain</td> <td align="left" valign="top" styleCode="Rrule">3.5</td> <td align="left" valign="top" styleCode="Rrule">3.5</td> <td align="left" valign="top" styleCode="Rrule">4.0</td> <td align="left" valign="top" styleCode="Rrule">4.0</td> <td align="left" valign="top">2.6</td> </tr> <tr ID="id_f383ff07-e847-4cb2-b7c4-b16323c80ca8"> <td align="left" valign="top" styleCode="Rrule">Nausea</td> <td align="left" valign="top" styleCode="Rrule">2.6</td> <td align="left" valign="top" styleCode="Rrule">3.3</td> <td align="left" valign="top" styleCode="Rrule">2.8</td> <td align="left" valign="top" styleCode="Rrule">2.9</td> <td align="left" valign="top">1.8</td> </tr> <tr ID="id_e3db58e2-337c-44fa-ac5d-1513f342a5f5"> <td align="left" valign="top" styleCode="Rrule">Upper Respiratory Tract Infection</td> <td align="left" valign="top" styleCode="Rrule">0.8</td> <td align="left" valign="top" styleCode="Rrule">2.9</td> <td align="left" valign="top" styleCode="Rrule">1.7</td> <td align="left" valign="top" styleCode="Rrule">1.9</td> <td align="left" valign="top">0.8</td> </tr> <tr ID="id_54121328-1374-4e66-82b4-cd0c7250b2ba"> <td align="left" valign="top" styleCode="Rrule">Vomiting</td> <td align="left" valign="top" styleCode="Rrule">0.8</td> <td align="left" valign="top" styleCode="Rrule">2.2</td> <td align="left" valign="top" styleCode="Rrule">1.4</td> <td align="left" valign="top" styleCode="Rrule">1.6</td> <td align="left" valign="top">1.1</td> </tr> <tr ID="id_c1301b6b-0d50-42f6-9817-740b980986a1" styleCode="Botrule"> <td align="left" valign="top" styleCode="Rrule">Flatulence</td> <td align="left" valign="top" styleCode="Rrule">0.6</td> <td align="left" valign="top" styleCode="Rrule">2.6</td> <td align="left" valign="top" styleCode="Rrule">1.4</td> <td align="left" valign="top" styleCode="Rrule">1.6</td> <td align="left" valign="top">1.2</td> </tr> </tbody> </table>