Mesalamine

Description

Each Mesalamine Delayed-Release Tablet, USP 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 g/mol. The tablet features a coating made of a pH-dependent polymer film that disintegrates at or above pH 6.8. Inactive ingredients in Mesalamine Delayed-Release Tablets, USP include colloidal silicon dioxide, magnesium stearate, carboxymethylcellulose sodium, sodium starch glycolate, hypromellose, microcrystalline cellulose, methacrylic acid-methyl methacrylate copolymer 1:1, methacrylic acid-methyl methacrylate copolymer 1:2, triethyl citrate, talc, polyvinyl alcohol, titanium dioxide, macrogol/PEG, iron oxide red, and iron oxide yellow.

Uses and Indications

Mesalamine delayed-release tablets are indicated for the induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis.

There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

Prior to initiating therapy with mesalamine delayed-release tablets, healthcare professionals should evaluate the patient's renal function and continue to monitor it periodically throughout the treatment.

Mesalamine delayed-release tablets must be swallowed whole; they should not be split or crushed. It is recommended that these tablets be administered with food to enhance absorption. Patients should also be advised to drink an adequate amount of fluids during treatment.

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.

Contraindications

Use of mesalamine delayed-release tablets is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any of the components of the formulation. 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 mesalamine delayed-release tablets and monitored periodically throughout the course of therapy. It is essential to evaluate the risks and benefits of mesalamine in patients with known renal impairment or those taking nephrotoxic medications. Should renal function deteriorate during treatment, mesalamine delayed-release tablets must be discontinued.

Healthcare professionals should be vigilant for signs of mesalamine-induced acute intolerance syndrome, as symptoms may closely resemble an exacerbation of ulcerative colitis. Continuous monitoring for worsening symptoms is advised, and treatment should be halted if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, necessitate immediate evaluation. If a hypersensitivity reaction is suspected, mesalamine delayed-release tablets should be discontinued without delay.

In patients with known liver impairment, careful consideration of the risks and benefits of mesalamine delayed-release tablets is warranted due to the potential for hepatic failure.

Severe cutaneous adverse reactions may occur; therefore, treatment should be discontinued at the first indication of such reactions or any other signs of hypersensitivity, with further evaluation considered.

Mesalamine delayed-release tablets are contraindicated in patients with upper gastrointestinal tract obstruction, including pyloric stenosis or other organic or functional obstructions.

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

Cases of nephrolithiasis have been reported in patients using mesalamine. It is important to note that mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is crucial.

The use of mesalamine may interfere with laboratory tests, particularly 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 and effective management.

Side Effects

Patients receiving mesalamine delayed-release tablets may experience a range of adverse reactions, which can be categorized into common and serious reactions.

The most common adverse reactions reported include headache, flatulence, abnormal liver function tests, abdominal pain, and diarrhea. These reactions were observed in clinical trials and may vary in frequency among patients.

Serious adverse reactions necessitate careful monitoring and management. Renal impairment is a significant concern; renal function should be assessed at the beginning of treatment and periodically thereafter. The risks and benefits of mesalamine delayed-release tablets should be evaluated in patients with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates during therapy, discontinuation of the medication is advised.

Mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Patients should be monitored for worsening symptoms, and treatment should be discontinued if acute intolerance syndrome is suspected. Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of mesalamine if suspected.

Hepatic failure is another serious risk; the use of mesalamine delayed-release tablets should be carefully considered in patients with known liver impairment. Severe cutaneous adverse reactions have been reported, and treatment should be stopped at the first signs or symptoms of such reactions or any other signs of hypersensitivity.

Upper gastrointestinal tract obstruction is a contraindication for mesalamine, particularly in patients with pyloric stenosis or other organic or functional obstructions. Patients with pre-existing skin conditions should be advised about photosensitivity and the importance of sun protection measures.

Nephrolithiasis has been reported in patients using mesalamine, and it is important to ensure adequate hydration during treatment, as mesalamine-containing stones may not be detectable by standard radiography or computed tomography (CT). Additionally, the use of mesalamine may interfere with laboratory tests, leading to spuriously elevated results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection.

Patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any of the ingredients in mesalamine delayed-release tablets, should not use this medication. Symptoms of salicylate toxicity, which may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures, should be monitored closely. Severe intoxication can lead to electrolyte and blood pH imbalances, potentially resulting in end-organ damage, including renal and liver impairment.

Drug Interactions

There are currently no documented drug interactions associated with the use of 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 Mesalamine, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of mesalamine delayed-release tablets have not been established in pediatric patients weighing less than 24 kg. Although pediatric use information is approved for LIALDA (mesalamine) delayed-release tablets by Takeda Pharmaceuticals U.S.A., Inc., the product is not labeled with this information due to the company's marketing exclusivity rights. Therefore, healthcare professionals should exercise caution when considering the use of this medication in younger patients or those below the specified weight threshold.

Geriatric Use

Clinical trials of mesalamine delayed-release tablets did not include a sufficient number 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 compared to their younger counterparts.

Elderly patients may experience increased systemic exposures to mesalamine. Therefore, it is essential to monitor complete blood cell counts and platelet counts in this population during treatment. Additionally, when prescribing mesalamine delayed-release tablets to geriatric 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 these 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 with 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. 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.

In women with ulcerative colitis, increased disease activity has been associated with a higher risk of adverse pregnancy outcomes, which may include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g), and small for gestational age infants at birth.

It is essential to consider that published epidemiologic studies have significant methodological limitations that may affect the interpretation of the data. These limitations include the inability to control for confounding factors such as underlying maternal disease, concomitant medication use, and incomplete information regarding the dose and duration of mesalamine use. Therefore, healthcare professionals should weigh the potential benefits of mesalamine treatment against the risks associated with untreated ulcerative colitis during pregnancy.

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.

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. The lack of clinical data during lactation limits the ability to clearly determine the risk of mesalamine delayed-release tablets to an infant during breastfeeding. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for mesalamine delayed-release tablets and any potential adverse effects on the breastfed child.

Caregivers should be advised to monitor breastfed infants for signs of diarrhea. 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.

Renal Impairment

Renal function should be assessed at the beginning of treatment and periodically during treatment for patients with renal impairment. It is important to evaluate the risks and benefits of mesalamine delayed-release tablets in patients with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates while on therapy, mesalamine delayed-release tablets should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using mesalamine delayed-release tablets. Due to the potential for altered pharmacokinetics in this population, it is essential to consider the degree of liver function compromise when prescribing this medication.

Monitoring of liver function is recommended for patients with known liver impairment to ensure safety and efficacy. Adjustments to the dosage may be necessary based on the severity of hepatic impairment, and close observation for any adverse effects is advised.

Overdosage

In cases of mesalamine overdose, healthcare professionals should be vigilant for symptoms indicative of salicylate toxicity. These symptoms may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and various neurologic manifestations such as headache, dizziness, confusion, and seizures.

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. Given the potential severity of these effects, prompt recognition and management of overdose are critical.

There is currently no specific antidote for mesalamine overdose; however, conventional therapies used for salicylate toxicity may provide beneficial effects in cases of acute overdosage. It is essential to consider the pharmacokinetics of mesalamine, particularly that the delayed-release tablets are pH-dependent. This characteristic should inform treatment strategies in suspected overdose scenarios.

Gastrointestinal decontamination may be warranted to prevent further absorption of the drug. This may involve the administration of activated charcoal, depending on the timing of the overdose and clinical judgment.

Management of fluid and electrolyte imbalances is crucial. Appropriate intravenous therapy should be initiated to correct these imbalances and to ensure adequate renal function is maintained throughout the treatment process. Continuous monitoring of the patient’s clinical status and laboratory parameters is recommended to guide further management and interventions.

Nonclinical Toxicology

In a 104-week dietary carcinogenicity study conducted in CD-1 mice, mesalamine administered at doses up to 2,500 mg/kg/day did not demonstrate tumorigenic potential. This dose is approximately 2.2 times the maximum recommended human dose based on a body surface area comparison for mesalamine delayed-release tablets. Similarly, a 104-week dietary carcinogenicity study in Wistar rats revealed that mesalamine at doses up to 800 mg/kg/day was also non-tumorigenic, representing 1.4 times the recommended human dose based on body surface area comparison.

No evidence of mutagenicity was observed in either an in vitro Ames test or an in vivo mouse micronucleus test, indicating that mesalamine does not possess mutagenic properties.

Regarding reproductive toxicity, no adverse effects on fertility or reproductive performance were noted in male or female rats administered oral doses of mesalamine up to 400 mg/kg/day, which is 0.7 times the maximum recommended human dose based on body surface area comparison.

In animal pharmacology and toxicology studies, the kidney was identified as the primary target organ for mesalamine toxicity. A 13-week oral toxicity study in mice, along with 13-week and 52-week oral toxicity studies in rats and cynomolgus monkeys, indicated that oral daily doses of 2,400 mg/kg in mice and 1,150 mg/kg in rats resulted in significant renal lesions. These lesions included 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

No specific postmarketing experience details are available. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Patients should be informed that mesalamine delayed-release tablets may decrease renal function, particularly in individuals with known renal impairment or those taking nephrotoxic medications. It is essential for patients to understand that periodic monitoring of renal function will be conducted during their therapy, and they should complete all blood tests as ordered by their healthcare provider.

Patients must be instructed to discontinue mesalamine delayed-release tablets 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. Additionally, patients should be advised to contact their healthcare provider if they have known liver disease and notice any signs or symptoms indicative of worsening liver function.

It is important to inform patients about the signs and symptoms of severe cutaneous adverse reactions. They should be instructed to stop taking mesalamine delayed-release tablets and report to their healthcare provider at the first appearance of any severe cutaneous adverse reaction or other signs of hypersensitivity. Patients should also be advised to reach out to their healthcare provider if they experience signs and symptoms of upper gastrointestinal tract obstruction.

For patients with pre-existing skin conditions, it is recommended 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 and to 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 made aware of the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. They should be encouraged to complete all blood tests as ordered by their healthcare provider.

Patients must be instructed to swallow mesalamine delayed-release tablets whole, without splitting or crushing them. It is also important to advise patients to take the tablets with food and to ensure they are drinking an adequate amount of fluids throughout their treatment.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20ºC to 25ºC (68ºF to 77ºF), with permissible excursions between 15ºC to 30ºC (59ºF to 86ºF). This storage condition aligns with the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature. Proper handling and storage are essential to maintain the integrity of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Mesalamine as submitted by Chartwell RX, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)