LIALDA® (mesalamine) delayed-release tablets

LIALDA® (mesalamine) delayed-release tablets

LIALDA® (mesalamine)

Each LIALDA delayed-release tablet for oral administration contains 1.2 g 5-aminosalicylic acid (5-ASA; mesalamine), an anti-inflammatory agent.

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.

INDICATIONS AND USAGE

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.

Mechanism of Action

The mechanism of action of mesalamine is not fully understood, but it appears to have a topical anti-inflammatory effect on the colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase and lipoxygenase pathways, is increased in patients with ulcerative colitis, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.

DOSAGE AND ADMINISTRATION

  • 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
  • Drink an adequate amount of fluids

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 PatientOnce Daily LIALDA Dosage
Week 0 to Week 8After Week 8
24 kg to 35 kg2.4 g (two 1.2-g tablets)1.2 g (one 1.2-g tablet)
Greater than 35 kg to 50 kg3.6 g (three 1.2-g tablets)2.4 g (two 1.2-g tablets)
Greater than 50 kg4.8 g (four 1.2-g tablets)2.4 g (two 1.2-g tablets)

CONTRAINDICATIONS

LIALDA is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or to any of the ingredients of LIALDA

WARNINGS AND PRECAUTIONS

Renal Impairment: Renal impairment, including minimal change disease, acute and chronic interstitial nephritis, and, rarely, renal failure, has been reported in patients given products such as LIALDA that contain mesalamine or are converted to mesalamine. In animal studies, the kidney was the principal organ of mesalamine toxicity.

Mesalamine-Induced Acute Intolerance Syndrome: Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from an exacerbation of ulcerative colitis. Although the exact frequency of occurrence has not been determined, it has occurred in 3% of patients in controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, acute abdominal pain, and bloody diarrhea, and sometimes fever, headache, and rash. Monitor patients closely for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with LIALDA.

Hypersensitivity Reactions: Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some of these patients may have a similar reaction to LIALDA tablets or to other compounds that contain or are converted to mesalamine.

Hepatic Failure: There have been reports of hepatic failure in patients with pre-existing liver disease who have been administered mesalamine. Evaluate the risks and benefits of using LIALDA in patients with known liver impairment.

Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of mesalamine. Discontinue LIALDA at the first appearance of signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Upper Gastrointestinal Tract Obstruction: Pyloric stenosis or other organic or functional obstruction in the upper gastrointestinal tract may cause prolonged gastric retention of LIALDA, which would delay mesalamine release in the colon. Avoid LIALDA in patients at risk of upper gastrointestinal tract obstruction.

Photosensitivity: Patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema have reported more severe photosensitivity reactions. Advise patients to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

Nephrolithiasis: Cases of nephrolithiasis have been reported with the use of mesalamine, including stones with a 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate hydration during treatment with LIALDA.

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.

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. Consider an alternative, selective assay for normetanephrine.

USE IN SPECIFIC POPULATIONS 

Pregnancy: Published data from meta-analyses, cohort studies, and case series on the use of mesalamine during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are adverse effects on maternal and fetal outcomes associated with ulcerative colitis in pregnancy.

Disease-associated maternal and embryo/fetal risk: Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

Lactation: Data from published literature report the presence of mesalamine and its metabolite, N-acetyl5-aminosalicylic acid in human milk in small amounts with relative infant doses (RID) of 0.1% or less for mesalamine. There are case reports of diarrhea in breastfed infants exposed to mesalamine. There is no information on the effects of the drug on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of LIALDA to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LIALDA and any potential adverse effects on the breastfed child from LIALDA or from the underlying maternal condition.

Renal Impairment: Mesalamine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Evaluate renal function in all patients prior to initiation and periodically while on LIALDA therapy. Monitor patients with known renal impairment or history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions.

OVERDOSAGE

LIALDA is an aminosalicylate, and symptoms of salicylate toxicity may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe intoxication with salicylates may lead to electrolyte and blood pH imbalance, and potentially end organ (e.g., renal and liver) damage.

There is no specific known antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent further absorption. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function.

LIALDA is a pH-dependent, delayed-release product and this factor should be considered when treating a suspected overdose.

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