LIALDA

Each LIALDA delayed-release tablet for oral administration contains 1.2 g 5-aminosalicylic acid (5-ASA; mesalamine), an anti-inflammatory agent. Mesalamine also has the chemical name 5-amino-2-hydroxybenzoic acid and its structural formula is: Molecular formula: C 7 H 7 NO 3 Molecular weight: 153.14 The tablet is coated with a pH-dependent polymer film, which breaks down at or above pH 6.8, normally in the terminal ileum where mesalamine then begins to be released from the tablet core. The tablet core contains mesalamine with hydrophilic and lipophilic excipients and provides for extended release of mesalamine. The inactive ingredients of LIALDA are sodium carboxymethylcellulose, carnauba wax, stearic acid, silica (colloidal hydrated), sodium starch glycolate (type A), talc, magnesium stearate, methacrylic acid copolymer types A and B, triethylcitrate, titanium dioxide, red ferric oxide, and polyethylene glycol 6000. Chemical Structure

LIALDA is indicated for the: induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis. treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg. LIALDA is an aminosalicylate indicated for the: induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis. ( 1 ) treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg. ( 1 )

Administration Instructions Evaluate renal function prior to initiation of LIALDA and periodically while on therapy. ( 2 , 5.1 ) Swallow LIALDA tablets whole; do not split or crush. ( 2 ) Administer LIALDA tablets with food. ( 2 ) Drink an adequate amount of fluids. ( 2 , 5.8 ) Recommended Dosage in Adults For induction of remission : 2.4 g to 4.8 g (two to four 1.2-g tablets) once daily. ( 2 ) For maintenance of remission : 2.4 g (two 1.2-g tablets) once daily. ( 2 ) Recommended Dosage in Pediatric Patients The recommended dosage for treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg who can swallow tablets whole is shown below: ( 2 ) Weight of Pediatric Patient Once Daily LIALDA Dosage Week 0 to Week 8 After Week 8 24 kg to 35 kg 2.4 g (two 1.2-g tablets) 1.2 g (one 1.2-g tablet) Greater than 35 kg to 50 kg 3.6 g (three 1.2-g tablets) 2.4 g (two 1.2-g tablets) Greater than 50 kg 4.8 g (four 1.2-g tablets) 2.4 g (two 1.2-g tablets) Administration Instructions Evaluate renal function prior to initiation of LIALDA and periodically while on therapy. Swallow LIALDA tablets whole; do not split or crush. Administer LIALDA tablets with food [see Clinical Pharmacology (12.3) ] . Drink an adequate amount of fluids [see Warnings and Precautions (5.8) ] . Adults The recommended dosage for the induction of remission in adult patients with mildly to moderately active ulcerative colitis is 2.4 g to 4.8 g (two to four 1.2-g tablets) taken once daily. The recommended dosage for the maintenance of remission is 2.4 g (two 1.2-g tablets) taken once daily. Pediatric Patients The recommended dosage for treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg who can swallow tablets whole is shown in Table 1: Table 1: Recommended Dosage of LIALDA for the Treatment of Mildly to Moderately Active Ulcerative Colitis in Pediatric Patients Weighing at least 24 kg Weight of Pediatric Patient Once Daily LIALDA Dosage Week 0 to Week 8 After Week 8 24 kg to 35 kg 2.4 g (two 1.2-g tablets) 1.2 g (one 1.2-g tablet) Greater than 35 kg to 50 kg 3.6 g (three 1.2-g tablets) 2.4 g (two 1.2-g tablets) Greater than 50 kg 4.8 g (four 1.2-g tablets) 2.4 g (two 1.2-g tablets)

LIALDA is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or to any of the ingredients of LIALDA [see Warnings and Precautions (5.3) , Adverse Reactions (6.2) , Description (11) ] . Known or suspected hypersensitivity to salicylates or aminosalicylates or to any of the ingredients of LIALDA. ( 4 )

The following clinically significant adverse reactions are described elsewhere in labeling: Renal impairment, including renal failure [see Warnings and Precautions (5.1) ] Mesalamine-induced acute intolerance syndrome [see Warnings and Precautions (5.2) ] Hypersensitivity reactions [see Warnings and Precautions (5.3) ] Hepatic failure [see Warnings and Precautions (5.4) ] Severe cutaneous adverse reactions [see Warnings and Precautions (5.5) ] Upper gastrointestinal tract obstruction [see Warnings and Precautions (5.6) ] Photosensitivity [see Warnings and Precautions (5.7) ] Nephrolithiasis [see Warnings and Precautions (5.8) ] Most common adverse reactions in: adults (≥2%) are headache, flatulence, liver function test abnormal, abdominal pain, and diarrhea. ( 6.1 ) pediatric patients (≥5%) are abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-800-828-2088 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. Adults Induction The most common adverse reactions occurring in at least 1% of LIALDA- or placebo-treated adult patients with mildly to moderately active ulcerative colitis in two eight-week, randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) [see Clinical Studies (14.1) ] are listed in Table 2. Table 2: Adverse Reactions Reported in at least 1% of patients in at least one LIALDA group and greater than placebo in Two Eight-Week, Placebo-Controlled Trials of Induction Therapy (Study 1 and Study 2) in Adults with Mildly to Moderately Active Ulcerative Colitis Adverse Reaction LIALDA 2.4 g once daily LIALDA 4.8 g once daily Placebo (n=177) (n=179) (n=179) Headache 6% 3% <1% Flatulence 4% 3% 3% Liver Function Test Abnormal <1% 2% 1% Alopecia 0 1% 0 Pruritus <1% 1% 1% Pancreatitis occurred in less than 1% of patients during induction in clinical trials and resulted in discontinuation of therapy with LIALDA in patients experiencing this event. Maintenance of Remission A LIALDA dosage of 2.4 g/day, administered as either 1.2 g twice daily or 2.4 g once daily, was evaluated for safety in three maintenance trials in patients with mildly to moderately active ulcerative colitis: a 6-month double-blind, active-controlled study (Study 3) [see Clinical Studies (14.1) ] and two 12- to 14-month open-label studies. The most common adverse reactions with LIALDA in these maintenance trials are listed in Table 3. Table 3: Adverse Reactions Reported in at least 1% of patients in Three Trials of Maintenance of Remission in Adults with Ulcerative Colitis LIALDA 2.4 g/day Administered either as 1.2 g twice daily or 2.4 g once daily (n=1082) Adverse Reaction % Headache 3% Liver function test abnormal 2% Abdominal pain 2% Diarrhea 2% Abdominal distension 1% Abdominal pain upper 1% Dyspepsia 1% Back pain 1% Rash 1% Arthralgia 1% Fatigue 1% Hypertension 1% The following adverse reactions, presented by body system, were reported in less than 1% of LIALDA-treated patients with ulcerative colitis in either induction or maintenance trials: Cardiac Disorder : tachycardia Ear and Labyrinth Disorders : ear pain Gastrointestinal Disorders : abdominal distention, colitis, diarrhea, flatulence, nausea, pancreatitis, rectal polyp, vomiting General Disorders and Administrative Site Disorders : asthenia, face edema, fatigue, pyrexia Investigations : decreased platelet count Musculoskeletal and Connective Tissue Disorders : arthralgia, back pain Nervous System Disorders : dizziness, somnolence, tremor Respiratory, Thoracic and Mediastinal Disorders : pharyngolaryngeal pain Skin and Subcutaneous Tissue Disorders : acne, prurigo, rash, alopecia, pruritus, urticaria Vascular Disorders : hypertension, hypotension Pediatrics LIALDA was evaluated in 105 pediatric patients 5 through 17 years of age with mildly to moderately active ulcerative colitis [see Clinical Studies (14.2) ] . The adverse reaction profile was similar to that of adults. The most common adverse reactions reported in at least 5% of pediatric patients treated with LIALDA were: abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LIALDA or other mesalamine-containing products. Because 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. Body as a Whole : lupus-like syndrome, drug fever Cardiac Disorders : pericarditis, pericardial effusion, myocarditis [see Warnings and Precautions (5.3) ] Gastrointestinal : cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer Hepatic : jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, hepatotoxicity, Kawasaki-like syndrome including changes in liver enzymes Hematologic : agranulocytosis, aplastic anemia Immune System Disorders : anaphylactic reaction, angioedema Musculoskeletal and Connective Tissue Disorders : myalgia, lupus-like syndrome Neurological/Psychiatric : peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis, intracranial hypertension Renal Disorders : renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis [see Warnings and Precautions (5.1 , 5.8) ] Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach Respiratory, Thoracic and Mediastinal Disorders : interstitial lung disease, hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis), pleurisy/pleuritis Skin : psoriasis, pyoderma gangrenosum, erythema nodosum, photosensitivity, SJS/TEN, DRESS, and AGEP [see Warnings and Precautions (5.5) ] Urogenital : reversible oligospermia

Nephrotoxic Agents including NSAIDs : Increased risk of nephrotoxicity; monitor for changes in renal function and mesalamine-related adverse reactions. ( 7.1 ) Azathioprine or 6-Mercaptopurine : Increased risk of blood dyscrasias; monitor complete blood cell counts and platelet counts. ( 7.2 ) 7.1 Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs The concurrent use of mesalamine with known nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs), may increase the risk of nephrotoxicity. Monitor patients taking nephrotoxic drugs for changes in renal function and mesalamine-related adverse reactions [see Warnings and Precautions (5.1) ] . 7.2 Azathioprine and 6-Mercaptopurine The concurrent use of mesalamine with azathioprine or 6-mercaptopurine and/or any other drugs known to cause myelotoxicity may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of LIALDA and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts. 7.3 Interference with Urinary Normetanephrine Measurements Use of LIALDA may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection [see Warnings and Precautions (5.9) ] . Consider an alternative, selective assay for normetanephrine.

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