Lialda

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in labeling:

• Renal impairment, including renal failure [see WARNINGS AND PRECAUTIONS]
• Mesalamine-induced acute intolerance syndrome [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
• Hepatic failure [see WARNINGS AND PRECAUTIONS]
• Upper gastrointestinal tract obstruction [see WARNINGS AND PRECAUTIONS]
• Photosensitivity [see WARNINGS AND PRECAUTIONS]
• Nephrolithiasis [see WARNINGS AND PRECAUTIONS]

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] are listed in Table 2.

Table 2: Adverse Reactions* 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 (n=177)	LIALDA 4.8 g once daily (n=179)	Placebo (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%
* Reported in at least 1% of patients in at least one LIALDA group and greater than placebo

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] 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* in Three Trials of Maintenance of Remission in Adults with Ulcerative Colitis

	LIALDA 2.4 g/day† (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%
* Reported in at least 1% of patients † Administered either as 1.2 g twice daily or 2.4 g once daily

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]. 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.

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]

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, Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS)

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]

Respiratory, Thoracic and Mediastinal Disorders: interstitial lung disease, hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis)

Skin: psoriasis, pyoderma gangrenosum, erythema nodosum, photosensitivity

Urogenital: reversible oligospermia

DRUG INTERACTIONS

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].

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.

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]. Consider an alternative, selective assay for normetanephrine.

Read the entire FDA prescribing information for Lialda (Mesalamine)