Mesalamine

Description

Each mesalamine capsule is a delayed- and extended-release dosage form intended for oral administration. Each capsule contains 0.375 g of mesalamine, USP (5-aminosalicylic acid, 5-ASA), an aminosalicylate, with a molecular weight of 153.14 and a molecular formula of C₇H₇NO₃. The extended-release capsules contain granules of mesalamine embedded in a polymer matrix, featuring an enteric coating that dissolves at a pH of 6 and above.

The inactive ingredients in the mesalamine extended-release capsules include microcrystalline cellulose, hypromellose, colloidal silicon dioxide, ethyl acrylate and methyl methacrylate 2:1 copolymer, magnesium stearate, methacrylic acid and methyl methacrylate 1:1 copolymer, talc, triethyl citrate, titanium dioxide, and hypromellose phthalate. The capsule shell is composed of titanium dioxide, FD&C Blue 1, FD&C Red 40, and gelatin, and is printed with edible black ink containing shellac, black iron oxide, and potassium hydroxide. It is important to note that FDA-approved dissolution test specifications differ from those of the USP.

Uses and Indications

Mesalamine extended-release capsule is indicated for the maintenance of remission of ulcerative colitis in adults.

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

Dosage and Administration

The recommended dosage of mesalamine extended-release capsules is 1.5 g, which corresponds to four 0.375 g capsules, administered once daily in the morning.

Prior to initiating therapy, healthcare professionals should evaluate the patient's renal function to ensure safety and efficacy. The capsules must be swallowed whole; they should not be cut, broken, crushed, or chewed, as this may affect the release mechanism of the medication.

Co-administration with antacids is not advised, as it may interfere with the therapeutic effects of mesalamine. Patients should be encouraged to drink an adequate amount of fluids while on this medication. Mesalamine extended-release capsules can be taken without regard to meals, allowing for flexibility in administration.

Contraindications

Use of mesalamine extended-release capsules is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or any component of the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Assessment of renal function is essential at the initiation of treatment and should be conducted periodically throughout the course of therapy. Healthcare professionals are advised to evaluate the risks and benefits of treatment in patients with known renal impairment or those concurrently using nephrotoxic medications. Continuous monitoring of renal function is imperative in these cases.

Healthcare providers should be vigilant for symptoms indicative of Mesalamine-Induced Acute Intolerance Syndrome, which may mimic an exacerbation of ulcerative colitis. It is crucial to monitor patients for any worsening of symptoms and to discontinue treatment if acute intolerance syndrome is suspected.

In cases where a hypersensitivity reaction is suspected, including but not limited to Myocarditis and Pericarditis, immediate evaluation of the patient is warranted, and treatment should be discontinued. Additionally, the risks and benefits of therapy should be carefully considered in patients with known liver impairment.

At the first signs or symptoms of severe cutaneous adverse reactions or any other indications of hypersensitivity, treatment should be discontinued, and further evaluation should be undertaken. Patients with pre-existing skin conditions are advised to minimize sun exposure, wear protective clothing, and utilize a broad-spectrum sunscreen when outdoors to mitigate the risk of skin reactions.

It is important to note that Mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). Therefore, ensuring adequate fluid intake during treatment is essential to prevent complications.

Healthcare professionals should also be aware that the use of mesalamine may result in spuriously elevated test results when measuring urinary Normetanephrine via liquid chromatography with electrochemical detection. Regular monitoring of renal function is recommended throughout the treatment period to ensure patient safety and treatment efficacy.

Side Effects

Patients may experience a range of adverse reactions while undergoing treatment. The most common adverse reactions, occurring in 3% or more of patients, include headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis.

Serious adverse reactions warrant careful monitoring and evaluation. Patients with known renal impairment or those taking nephrotoxic drugs should have their renal function assessed at the beginning of treatment and periodically thereafter. It is essential to evaluate the risks and benefits of treatment in these patients and to monitor renal function closely.

Mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Therefore, it is crucial to monitor for any worsening symptoms and to discontinue treatment if acute intolerance syndrome is suspected. Additionally, hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of the medication if such reactions are suspected.

Patients with known liver impairment should also be evaluated for the risks and benefits of treatment, as hepatic failure has been reported. Severe cutaneous adverse reactions necessitate discontinuation of the medication at the first signs or symptoms, along with consideration for further evaluation.

Photosensitivity is another concern; patients with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. Furthermore, nephrolithiasis has been noted, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate fluid intake during treatment is recommended to mitigate this risk.

It is important to note that 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, aminosalicylates, or any component of mesalamine extended-release capsules should not use this medication.

In cases of overdosage, symptoms of salicylate toxicity may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication can lead to electrolyte and blood pH imbalances, potentially resulting in damage to other organs, including the kidneys and liver.

Drug Interactions

The concomitant use of nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), may lead to an increased risk of nephrotoxicity. It is recommended to monitor renal function closely and observe for any adverse reactions related to mesalamine.

When azathioprine or 6-mercaptopurine is administered concurrently, there is an elevated risk of blood disorders. Regular monitoring of complete blood cell counts and platelet counts is advised to detect any potential hematological complications.

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 in pediatric patients have not been established. Therefore, caution is advised when considering the use of this medication in children and adolescents. Further studies are needed to determine appropriate dosing and outcomes in this population.

Geriatric Use

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

Given these findings, it is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine. Additionally, when prescribing mesalamine to geriatric patients, healthcare providers should consider the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies that may affect treatment outcomes. Careful assessment and monitoring are recommended to ensure the safety and efficacy of mesalamine in this population.

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. In animal reproduction studies, administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.7 and 5.4 times, respectively, the maximum recommended human dose did not result in adverse developmental outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown. It is important to note that adverse outcomes in pregnancy can occur regardless of maternal health or medication use. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2 to 4% and 15 to 20%, respectively.

In women with ulcerative colitis, published data suggest that increased disease activity 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 infants at birth.

While 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 interpretation of existing epidemiologic studies is complicated by methodological limitations. These limitations include the inability to control for confounding factors such as underlying maternal disease and concomitant medication use, as well as gaps in information regarding the dose and duration of mesalamine use.

Healthcare professionals should consider these factors when prescribing mesalamine to pregnant patients and weigh the potential benefits against any risks, particularly in the context of the patient's disease activity and overall health.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers. Additionally, there is no data on the potential for excretion of this medication in breast milk or its effects on breastfed infants. Healthcare professionals should consider the lack of information when advising lactating mothers on the use of this medication.

Renal Impairment

Renal function should be assessed at the beginning of treatment and periodically throughout the course of therapy in patients with renal impairment. It is essential to evaluate the risks and benefits of treatment in these patients, particularly those with known renal impairment or those taking nephrotoxic drugs, and to monitor renal function closely.

Healthcare professionals should ensure that patients maintain adequate fluid intake during treatment to prevent nephrolithiasis. It is important to note that mesalamine-containing stones may be undetectable by standard radiography or computed tomography (CT).

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of treatment. It is essential to assess liver function prior to initiating therapy and to monitor liver parameters throughout the course of treatment. Adjustments to dosage may be necessary based on the severity of liver impairment. Close monitoring of liver function tests is recommended to ensure patient safety and to mitigate potential adverse effects associated with compromised liver function.

Overdosage

In cases of mesalamine overdosage, 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 salicylate intoxication can result in significant complications, including electrolyte and blood pH imbalances, which may lead to damage of vital organs, particularly the kidneys and liver.

Currently, there is no specific antidote available for mesalamine overdose. However, conventional treatment strategies for salicylate toxicity may be employed effectively in cases of acute overdosage. Initial management should focus on gastrointestinal decontamination to prevent further absorption of the drug.

It is crucial to address any fluid and electrolyte imbalances that may arise. This can be achieved through the administration of appropriate intravenous therapy, ensuring that renal function is adequately maintained throughout the treatment process.

Additionally, it is important to consider that mesalamine is a pH-dependent delayed-release formulation, which may influence the approach to treatment in suspected overdose scenarios.

Nonclinical Toxicology

Dietary mesalamine was evaluated for carcinogenic potential in both rats and mice. In these studies, mesalamine did not demonstrate carcinogenicity at doses of up to 480 mg/kg/day in rats and 2000 mg/kg/day in mice. These doses correspond to approximately 2.6 and 5.4 times the recommended human dose of granulated mesalamine capsules, which is 1.5 g/day, based on body surface area.

In terms of mutagenicity, mesalamine was found to be negative in several assays, including the Ames test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, the sister chromatid exchange assay in the Chinese hamster bone marrow test, and the mouse bone marrow micronucleus test.

No adverse effects on fertility or reproductive performance were observed in male and female rats administered oral doses of mesalamine up to 320 mg/kg, which is approximately 1.7 times the recommended human dose based on body surface area.

Animal studies, including 13-week and 26-week oral toxicity studies in rats, as well as 26-week and 52-week oral toxicity studies in dogs, identified the kidney as the primary target organ for mesalamine toxicity. Lethal doses of mesalamine were determined to be 800 mg/kg in mice and 1800 mg/kg in rats, which are approximately 2.2 and 9.7 times the recommended human dose based on body surface area, respectively. These doses resulted in gastrointestinal and renal toxicity.

At lower oral doses of 40 mg/kg/day, which is about 0.20 times the human dose based on body surface area, minimal to slight tubular injury was noted. Doses of 160 mg/kg/day or higher, approximately 0.90 times the human dose, led to renal lesions in rats, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, in dogs, oral doses of 60 mg/kg/day or higher, about 1.1 times the human dose based on body surface area, resulted in renal lesions such as tubular atrophy, interstitial cell infiltration, chronic nephritis, and papillary necrosis.

Postmarketing Experience

No postmarketing experience details are available in the provided text.

Patient Counseling

Healthcare providers should advise patients to swallow the mesalamine extended-release capsules whole and to avoid cutting, breaking, crushing, or chewing the capsules, as this may affect the medication's efficacy.

Patients should be informed to avoid co-administration of mesalamine extended-release capsules with antacids, as this may interfere with the medication's absorption and effectiveness.

It is important to encourage patients to drink an adequate amount of fluids while taking this medication to help maintain hydration and support overall health.

Additionally, healthcare providers can inform patients that mesalamine extended-release capsules can be taken without regard to meals, providing flexibility in their dosing schedule.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a controlled room temperature of 25°C (77°F). Temporary excursions are permitted within the range of 15°C to 30°C (59°F to 86°F) in accordance with USP guidelines for controlled room temperature. Proper storage conditions are essential to maintain the integrity and efficacy 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 Alembic Pharmaceuticals Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)