Side Effects of Lialda (mesalamine)

Lialda (mesalamine) is an anti-inflammatory agent used to treat active, mild to moderate ulcerative colitis. 

Lialda is mesalamine in a form that is slowly released in the intestine so that it can be given just once-a-day. Other oral drugs containing mesalamine that are similar to Lialda include Asacol, Pentasa, and Apriso. Asacol and Pentasa, however, are given as multiple daily doses. 

The exact mechanism of Lialda is not known but is believed to be by reducing inflammation in the colon. Ulcerative colitis and other inflammatory diseases cause excessive production of chemicals (i.e., prostaglandins) that produce inflammation in the colon.

Prostaglandins are produced by cyclooxygenase and lipoxygenase enzymes. These enzymes are over-active in individuals with ulcerative colitis. Lialda may work by blocking the activity of cyclooxygenase and lipoxygenase, therefore, reducing the production of prostaglandins. Reduced prostaglandin production reduces inflammation in the colon and other symptoms associated with ulcerative colitis.

Common side effects of Lialda include

• headache,
• gas (flatulence),
• hair loss, and
• itching.

Less common side effects of Lialda include

• increased heart rate,
• acne,
• back pain,
• fatigue,
• tremor, and
• ear pain.

Serious side effects of Lialda include

• pancreatitis,
• blood disorders,
• kidney dysfunction and
• an acute intolerance syndrome that resembles a flare of inflammatory bowel disease. Symptoms include
  • cramping,
  • acute abdominal pain,
  • bloody diarrhea,
  • fever,
  • headache,
  • itching, and
  • rash.

Specific drug interaction studies have not been conducted with Lialda. Other mesalamine medications have been associated with several drug interactions.

Combining mesalamine with drugs that affect kidney function, for example, nonsteroidal anti-inflammatory drugs (for example, ibuprofen), may increase the likelihood of kidney dysfunction. Concurrent use of mesalamine and 6-mercaptopurine or azathioprine may increase the likelihood of blood disorders. Mesalamine may increase the blood thinning effect of warfarin.

There are no adequate human studies of Lialda use during pregnancy. Lialda should only be used during pregnancy if it is felt that the benefit of its use justifies the unknown risks.

Lialda is excreted in breast milk. Lialda should only be used by breastfeeding mothers if it is felt the benefit of its use justifies the risk.

The most common side effects are:

• headache,
• flatulence,
• hair loss, and
• itching.

Other less common side effects include:

• increased heart rate,
• acne,
• pancreatitis,
• back pain,
• fatigue,
• tremor,
• ear pain,
• blood disorders, and
• kidney dysfunction.

Possible serious side effects include an acute intolerance syndrome that resembles a flare of inflammatory bowel disease. Symptoms include:

• cramping,
• acute abdominal pain, 
• bloody diarrhea,
• fever,
• headache,
• itching, and
• rash.

These symptoms usually subside once mesalamine is discontinued. Since mesalamine is related chemically to aspirin, individuals who are allergic to aspirin should not take mesalamine.

The most serious adverse reactions seen in Lialda clinical trials or with other products that contain or are metabolized to mesalamine are:

• Renal impairment, including renal failure
• Mesalamine-induced acute intolerance syndrome
• Hypersensitivity reactions
• Hepatic impairment

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) 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

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) 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

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. 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

In addition to the adverse reactions reported above in clinical trials involving Lialda, the adverse reactions listed below have been identified during postapproval use of Lialda and 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

Gastrointestinal: cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer

Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, 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-Barre syndrome, transverse myelitis, intracranial hypertension

Renal Disorders: renal failure, interstitial nephritis, nephrogenic diabetes insipidus

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

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.

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 Laboratory Tests

Use of Lialda may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection. Consider an alternative, selective assay for normetanephrine.