Lialda

Description

Each LIALDA delayed-release tablet for oral administration contains 1.2 g of 5-aminosalicylic acid (5-ASA; mesalamine), which serves as an anti-inflammatory agent. Mesalamine is chemically identified as 5-amino-2-hydroxybenzoic acid, with a molecular formula of C7H7NO3 and a molecular weight of 153.14. The tablet is coated with a pH-dependent polymer film that disintegrates at or above pH 6.8. The core of the tablet comprises mesalamine along with hydrophilic and lipophilic excipients, facilitating the extended release of mesalamine. Inactive ingredients include sodium carboxymethylcellulose, carnauba wax, stearic acid, colloidal hydrated silica, 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.

Uses and Indications

LIALDA is indicated for the induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis. Additionally, LIALDA is indicated for the treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg.

There are no teratogenic or nonteratogenic effects associated with LIALDA.

Dosage and Administration

Healthcare professionals should evaluate renal function prior to the initiation of LIALDA and periodically during therapy. LIALDA tablets must be swallowed whole; they should not be split or crushed. It is recommended to administer LIALDA tablets with food and ensure that patients drink an adequate amount of fluids.

For adults, the recommended dosage for the induction of remission is between 2.4 g to 4.8 g, which corresponds to two to four 1.2-g tablets taken once daily. For the maintenance of remission, the recommended dosage is 2.4 g, equivalent to two 1.2-g tablets, taken once daily.

In pediatric patients weighing at least 24 kg who can swallow tablets whole, the recommended dosages for the treatment of mildly to moderately active ulcerative colitis are as follows:

• For patients weighing 24 kg to 35 kg:

  • Week 0 to Week 8: 2.4 g (two 1.2-g tablets) once daily.

  • After Week 8: 1.2 g (one 1.2-g tablet) once daily.

• For patients weighing greater than 35 kg to 50 kg:

  • Week 0 to Week 8: 3.6 g (three 1.2-g tablets) once daily.

  • After Week 8: 2.4 g (two 1.2-g tablets) once daily.

• For patients weighing greater than 50 kg:

  • Week 0 to Week 8: 4.8 g (four 1.2-g tablets) once daily.

  • After Week 8: 2.4 g (two 1.2-g tablets) once daily.

Contraindications

Use of LIALDA is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, as well as to any of the product's ingredients. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Renal function should be assessed at the initiation of treatment with LIALDA and monitored periodically throughout the course of therapy. It is essential to evaluate the risks and benefits of LIALDA in patients with known renal impairment or those taking nephrotoxic medications. Should renal function deteriorate during treatment, LIALDA must be discontinued.

Healthcare professionals should be vigilant for symptoms of Mesalamine-Induced Acute Intolerance Syndrome, which may mimic an exacerbation of ulcerative colitis. Monitoring for any worsening of symptoms is crucial, and treatment should be discontinued if acute intolerance syndrome is suspected.

Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, LIALDA should be discontinued without delay. Additionally, the use of LIALDA in patients with known liver impairment necessitates a careful assessment of the associated risks and benefits.

Severe cutaneous adverse reactions have been reported; therefore, treatment should be halted at the first indication of such reactions or any other signs of hypersensitivity, with further evaluation considered. LIALDA is contraindicated in patients with pyloric stenosis or any other organic or functional obstruction of the upper gastrointestinal tract.

Patients should be advised about the risk of photosensitivity. Those with pre-existing skin conditions should take precautions to avoid sun exposure, including wearing protective clothing and using a broad-spectrum sunscreen when outdoors.

Nephrolithiasis has been associated with mesalamine use. It is important to note that mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). To mitigate this risk, patients should be encouraged to maintain adequate hydration during treatment.

In addition to these warnings, healthcare professionals should be aware that the use of mesalamine may interfere with laboratory tests, specifically leading to spuriously elevated results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection. Regular assessment of renal function is recommended at the beginning of treatment and periodically thereafter to ensure patient safety.

Side Effects

Patients receiving treatment may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Most common adverse reactions observed in clinical trials for adults (≥2%) include headache, flatulence, liver function test abnormalities, abdominal pain, and diarrhea. In pediatric patients (≥5%), the most frequently reported adverse reactions are abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection.

In clinical trials, the following adverse reactions were noted during the induction phase for adults: headache (6%), flatulence (4%), and liver function test abnormalities (<1%, with an increase to 2% for a dosage of 4.8 g once daily). Other reactions included alopecia (1%) and pruritus (<1%, with 1% for both doses). During the maintenance of remission phase, headache (3%), liver function test abnormalities (2%), abdominal pain (2%), and diarrhea (2%) were the most common. Additional reactions reported at a frequency of 1% or less included abdominal distension, upper abdominal pain, dyspepsia, back pain, rash, arthralgia, fatigue, and hypertension. Less than 1% of participants experienced tachycardia, ear pain, gastrointestinal disorders (including abdominal distention, colitis, nausea, and vomiting), general disorders (such as asthenia and pyrexia), musculoskeletal disorders (including arthralgia and back pain), nervous system disorders (such as dizziness and tremor), respiratory disorders (pharyngolaryngeal pain), skin disorders (including acne and urticaria), and vascular disorders (hypertension and hypotension).

Postmarketing experience has revealed additional serious adverse reactions. These include lupus-like syndrome, drug fever, pericarditis, myocarditis, gastrointestinal complications (such as cholecystitis and gastrointestinal bleeding), hepatic issues (including jaundice and liver failure), hematologic disorders (such as agranulocytosis), immune system disorders (including anaphylactic reactions), neurological and psychiatric disorders (such as Guillain-Barré syndrome), renal disorders (including renal failure), respiratory disorders (such as interstitial lung disease), severe cutaneous adverse reactions (including SJS/TEN), and urogenital issues (reversible oligospermia).

It is important to assess renal function at the beginning of treatment and periodically thereafter, discontinuing therapy if renal function deteriorates. Patients should be monitored for mesalamine-induced acute intolerance syndrome, which may mimic an exacerbation of ulcerative colitis. Hypersensitivity reactions, including myocarditis and pericarditis, necessitate immediate evaluation and discontinuation of treatment if suspected. Caution is advised in patients with known liver impairment due to the risk of hepatic failure. Patients should also be informed about the potential for nephrolithiasis and the need for adequate hydration during treatment. Furthermore, the use of mesalamine may interfere with laboratory tests, leading to spuriously elevated results in certain assays.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Lialda (mesalamine), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of LIALDA have been established for the treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg. Evidence supporting its use in this population includes data from adequate and well-controlled trials in adults, as well as a multicenter, randomized, double-blind, parallel group trial involving 105 pediatric patients aged 5 to 17 years.

The safety profile observed in pediatric patients was similar to that reported in adults. However, the safety and effectiveness of LIALDA have not been established in patients weighing less than 24 kg.

Geriatric Use

Clinical trials of LIALDA did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. However, reports from uncontrolled clinical studies and postmarketing surveillance have indicated a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients taking mesalamine-containing products such as LIALDA compared to their younger counterparts.

Elderly patients may experience increased systemic exposures to LIALDA. Therefore, it is essential to monitor complete blood cell counts and platelet counts in this population during treatment. Additionally, when prescribing LIALDA to elderly patients, healthcare providers should consider the greater frequency of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

It is advisable to consider starting treatment at the low end of the dosing range for induction in elderly patients to mitigate potential risks associated with higher systemic exposure and to account for the aforementioned factors.

Pregnancy

Published data from meta-analyses, cohort studies, and case series regarding the use of mesalamine during pregnancy have not consistently demonstrated an association between mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, it is important to note that adverse effects on maternal and fetal outcomes are associated with ulcerative colitis during pregnancy.

In animal reproduction studies, administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.8 and 2.9 times, respectively, the maximum recommended human dose did not result in adverse developmental outcomes. Additionally, there is no clear evidence that mesalamine exposure in early pregnancy is linked to an increased risk of major congenital malformations, including cardiac malformations.

The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is approximately 2% to 4% and 15% to 20%, respectively.

It is also noted that increased disease activity in women with ulcerative colitis is associated with a higher risk of adverse pregnancy outcomes, which may include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g), and small for gestational age at birth. Therefore, healthcare providers should consider the potential risks associated with uncontrolled disease activity when managing pregnant patients with ulcerative colitis.

Lactation

Data from published literature indicate that mesalamine and its metabolite, N-acetyl-5-aminosalicylic acid, are present in human milk in small amounts. The relative infant doses (RID) for mesalamine are reported to be 0.1% or less. In lactation studies, maternal doses of mesalamine from various oral and rectal formulations ranged from 500 mg to 4.8 g daily. The average concentration of mesalamine in breast milk ranged from non-detectable to 0.5 mg/L, while the average concentration of N-acetyl-5-aminosalicylic acid ranged from 0.2 to 9.3 mg/L.

Estimated daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day for mesalamine (RID 0% to 0.1%) and 0.03 to 1.4 mg/kg/day for N-acetyl-5-aminosalicylic acid. There have been case reports of diarrhea in breastfed infants exposed to mesalamine. However, there is no information available regarding the effects of mesalamine on milk production.

Due to the lack of clinical data during lactation, a clear determination of the risk of LIALDA to a nursing infant cannot be made. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for LIALDA and any potential adverse effects on the breastfed child from LIALDA or from the underlying maternal condition. Caregivers should be advised to monitor breastfed infants for signs of diarrhea.

Renal Impairment

Patients with renal impairment may experience an increased risk of toxic reactions due to the substantial renal excretion of mesalamine. It is essential to evaluate renal function in all patients prior to the initiation of LIALDA therapy and to conduct periodic assessments throughout treatment.

For patients with known renal impairment, a history of renal disease, or those taking nephrotoxic drugs, close monitoring for decreased renal function and mesalamine-related adverse reactions is recommended. The risks and benefits of continuing LIALDA therapy should be carefully assessed in these patients. If renal function deteriorates during treatment, LIALDA should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using LIALDA. Due to the potential for altered pharmacokinetics in this population, it is essential to consider the degree of liver function compromise when determining the appropriateness of treatment. Monitoring of liver function tests may be warranted to ensure patient safety and to assess the need for any dosage adjustments. It is recommended that healthcare providers exercise caution and closely observe patients with known liver impairment throughout the course of therapy.

Overdosage

In cases of overdose, symptoms of salicylate toxicity may manifest as nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and various neurologic symptoms, including headache, dizziness, confusion, and seizures. It is crucial for healthcare professionals to recognize these signs promptly to initiate appropriate management.

Severe intoxication with salicylates can result in significant electrolyte and blood pH imbalances, which may lead to end organ damage, particularly affecting renal and liver function. Therefore, monitoring and addressing these potential complications is essential in the management of overdose cases.

Currently, there is no specific antidote for mesalamine overdose. However, conventional therapy for salicylate toxicity may provide beneficial effects in acute overdose situations. Healthcare providers should consider gastrointestinal tract decontamination to prevent further absorption of the drug, which may be necessary in the event of an overdose.

Management of fluid and electrolyte imbalances is critical. Appropriate intravenous therapy should be administered to correct these imbalances and to maintain adequate renal function. Given that LIALDA is a pH-dependent, delayed-release formulation, this characteristic should be taken into account when treating a suspected overdose, as it may influence the pharmacokinetics and overall management strategy.

Nonclinical Toxicology

In nonclinical studies, mesalamine has been evaluated for its potential toxicological effects.

No information regarding teratogenic effects was provided. However, non-teratogenic effects were assessed, revealing no adverse effects on fertility or reproductive performance in male or female rats at oral doses of mesalamine up to 400 mg/kg/day, which corresponds to 0.7 times the maximum recommended human dose based on a body surface area comparison.

In a 104-week dietary carcinogenicity study conducted in CD-1 mice, mesalamine administered at doses up to 2500 mg/kg/day did not demonstrate tumorigenic potential. This dose is 2.2 times the maximum recommended human dose based on a body surface area comparison for LIALDA. Similarly, a 104-week dietary carcinogenicity study in Wistar rats showed that mesalamine at doses up to 800 mg/kg/day was not tumorigenic, equating to 1.4 times the recommended human dose based on a body surface area comparison for LIALDA. Additionally, no evidence of mutagenicity was observed in either an in vitro Ames test or an in vivo mouse micronucleus test.

Animal studies have identified the kidney as the primary target organ for mesalamine toxicity. In a 13-week oral toxicity study in mice, as well as 13-week and 52-week oral toxicity studies in rats and cynomolgus monkeys, significant renal lesions were noted. In mice, oral daily doses of 2400 mg/kg resulted in renal lesions such as granular and hyaline casts, tubular degeneration, tubular dilation, renal infarct, papillary necrosis, tubular necrosis, and interstitial nephritis. In cynomolgus monkeys, oral daily doses of 250 mg/kg or higher led to nephrosis, papillary edema, and interstitial fibrosis.

Postmarketing Experience

During post-approval use of LIALDA and other mesalamine-containing products, various adverse reactions have been reported voluntarily or through surveillance programs. Due to the nature of these reports, which originate from a population of uncertain size, it is not always feasible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Reports include lupus-like syndrome and drug fever.

Cardiac Disorders: Adverse events such as pericarditis, pericardial effusion, and myocarditis have been noted.

Gastrointestinal Disorders: Cases of cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, and perforated peptic ulcer have been identified.

Hepatic Disorders: Instances of jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, hepatotoxicity, and Kawasaki-like syndrome with changes in liver enzymes have been reported.

Hematologic Disorders: Reports of agranulocytosis and aplastic anemia have been documented.

Immune System Disorders: Adverse reactions including anaphylactic reactions and angioedema have been observed.

Musculoskeletal and Connective Tissue Disorders: Myalgia and lupus-like syndrome have been reported.

Neurological/Psychiatric Disorders: Cases of peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis, and intracranial hypertension have been noted.

Renal Disorders: Reports of renal failure, interstitial nephritis, nephrogenic diabetes insipidus, and nephrolithiasis have been identified.

Urine discoloration has been observed ex-vivo due to contact of mesalamine, including its inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Respiratory, Thoracic and Mediastinal Disorders: Adverse events such as interstitial lung disease and hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, and eosinophilic pneumonitis), as well as pleurisy/pleuritis, have been reported.

Skin Disorders: Reports include psoriasis, pyoderma gangrenosum, erythema nodosum, photosensitivity, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

Urogenital Disorders: Reversible oligospermia has been documented.

Patient Counseling

Patients should be informed that LIALDA may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic medications. Periodic monitoring of renal function will be conducted during therapy, and patients are advised to complete all blood tests ordered by their healthcare provider.

Patients should be instructed to discontinue LIALDA and promptly report to their healthcare provider if they experience new or worsening symptoms of acute intolerance syndrome, which may include cramping, abdominal pain, bloody diarrhea, fever, headache, and rash, as well as any symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, it is important to contact their healthcare provider if they notice any signs or symptoms indicative of worsening liver function. Additionally, patients should be made aware of the signs and symptoms of severe cutaneous adverse reactions. They should stop taking LIALDA and report to their healthcare provider at the first appearance of such reactions or any other signs of hypersensitivity.

Patients experiencing signs and symptoms of upper gastrointestinal tract obstruction should also reach out to their healthcare provider. Those with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

Patients should be instructed to maintain adequate fluid intake during treatment to minimize the risk of kidney stone formation. They should contact their healthcare provider if they experience signs or symptoms of a kidney stone, such as severe side or back pain or blood in the urine.

Elderly patients and those taking azathioprine or 6-mercaptopurine should be informed of the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. It is essential for these patients to complete all blood tests ordered by their healthcare provider.

Patients should be instructed to swallow LIALDA tablets whole, without splitting or crushing them, and to take the tablets with food. They should also be informed that urine may become discolored reddish-brown while taking LIALDA when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. If discolored urine is observed, patients should monitor their urine flow and report to their healthcare provider only if the urine is discolored upon leaving the body, prior to contact with any surface or water.

Lastly, patients are advised to ensure adequate fluid intake throughout their treatment.

Storage and Handling

LIALDA is supplied in an HDPE bottle equipped with a child-resistant closure. The product should be stored at room temperature, specifically between 15°C to 25°C (59°F to 77°F). Temporary excursions to a maximum temperature of 30°C (86°F) are permissible. It is recommended to refer to the USP Controlled Room Temperature guidelines for further details on storage conditions.

Additional Clinical Information

Postmarketing experience has revealed a range of adverse events associated with the use of the medication. Clinicians should be aware of potential systemic reactions such as lupus-like syndrome and drug fever. Cardiac disorders may include pericarditis, pericardial effusion, and myocarditis. Gastrointestinal complications can manifest as cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, and perforated peptic ulcer.

Hepatic effects reported include jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, and hepatotoxicity, with some cases resembling Kawasaki-like syndrome characterized by changes in liver enzymes. Hematologic issues such as agranulocytosis and aplastic anemia have also been noted. Immune system disorders may present as anaphylactic reactions and angioedema. Musculoskeletal and connective tissue disorders include myalgia and lupus-like syndrome.

Neurological and psychiatric effects can involve peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis, and intracranial hypertension. Renal disorders reported include renal failure, interstitial nephritis, nephrogenic diabetes insipidus, and nephrolithiasis. Additionally, urine discoloration may occur ex-vivo due to contact with surfaces or water treated with hypochlorite-containing bleach. Respiratory, thoracic, and mediastinal disorders such as interstitial lung disease and hypersensitivity pneumonitis have been observed, along with skin reactions including psoriasis, pyoderma gangrenosum, erythema nodosum, photosensitivity, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Lastly, reversible oligospermia has been reported in the urogenital category.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Lialda as submitted by Takeda Pharmaceuticals America, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)