Mesalamine

Description

Each mesalamine extended-release 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 capsules contain granules composed of mesalamine within a polymer matrix, featuring an enteric coating that dissolves at a pH of 6 and above.

Inactive ingredients include microcrystalline cellulose, ethyl acrylate and methyl methacrylate copolymer nonoxynol 100 dispersion, colloidal silicon dioxide, magnesium stearate, methacrylic acid and methyl methacrylate copolymer, sodium lauryl sulfate, talc, triethyl citrate, hypromellose, titanium dioxide, polyethylene glycol, vanillin, gelatin, FD and C Blue #1, FD and C Red #3, and edible black ink, which contains shellac, propylene glycol, black iron oxide, and potassium hydroxide. It is important to note that FDA-approved dissolution test specifications differ from USP acceptance criteria.

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 absorption 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

Renal function should be assessed at the initiation of treatment and monitored periodically throughout the course of therapy. It is essential to evaluate the risks and benefits of treatment in patients with known renal impairment or those taking nephrotoxic medications. Close monitoring of renal function is advised in these populations.

Patients should be vigilant for symptoms of Mesalamine-Induced Acute Intolerance Syndrome, which may mimic an exacerbation of ulcerative colitis. If acute intolerance syndrome is suspected, treatment should be discontinued, and the patient's condition should be closely monitored for any worsening symptoms.

Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, treatment must be discontinued promptly.

In patients with known liver impairment, a careful assessment of the risks and benefits of treatment is necessary due to the potential for hepatic failure.

Severe cutaneous adverse reactions can occur; therefore, treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation may be warranted in these cases.

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

Nephrolithiasis is a potential risk, as mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). To reduce the risk of stone formation, it is crucial to ensure adequate fluid intake during treatment.

It is important to note that the use of mesalamine may interfere with laboratory tests, specifically leading to spuriously elevated results when measuring urinary normetanephrine using 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 treatment efficacy.

Side Effects

Most common adverse reactions observed in clinical trials, occurring in 3% or more of patients, include headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis.

Serious adverse reactions may occur, including renal impairment, which necessitates assessment of renal function at the beginning of treatment and periodically thereafter. It is important to evaluate the risks and benefits in patients with known renal impairment or those taking nephrotoxic drugs, and to monitor renal function closely.

Mesalamine-induced acute intolerance syndrome can present with symptoms that may be 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 treatment if a hypersensitivity reaction is suspected. Additionally, severe cutaneous adverse reactions warrant discontinuation at the first signs or symptoms, along with consideration for further evaluation.

Patients with known liver impairment should be carefully evaluated for the risks and benefits of treatment, as hepatic failure is a potential concern.

Nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Patients should be advised to ensure adequate fluid intake during treatment to mitigate this risk.

Photosensitivity is another consideration; patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

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.

Additional adverse reactions may include known or suspected hypersensitivity to salicylates, aminosalicylates, or any component of mesalamine extended-release capsules. Symptoms of salicylate toxicity can manifest as nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication may result in electrolyte and blood pH imbalances, potentially leading to damage to other organs, including renal and hepatic systems.

Drug Interactions

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

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

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 extended-release capsules 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 necessary to determine appropriate dosing and therapeutic outcomes in this population.

Geriatric Use

Clinical studies of mesalamine extended-release capsules did not include a sufficient number of subjects aged 65 years and older to determine whether these elderly patients 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 using mesalamine-containing products.

Given these findings, it is essential to monitor complete blood cell counts and platelet counts in geriatric patients during treatment with mesalamine extended-release capsules. Additionally, when prescribing this medication to elderly 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 extended-release capsules 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 missing information regarding the dose and duration of mesalamine use.

Healthcare professionals should consider these factors when counseling pregnant patients or women of childbearing potential regarding the use of mesalamine.

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 about the use of this medication.

Renal Impairment

Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically throughout the course of therapy. It is essential to evaluate the risks and benefits in patients with known renal impairment or those taking nephrotoxic drugs, with close monitoring of renal function recommended.

Additionally, patients should be informed about the risk of nephrolithiasis, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). To mitigate this risk, ensuring adequate fluid intake during treatment is advised.

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 treatment course. Adjustments to the 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 the event of an overdose of mesalamine extended-release capsules, which are classified as aminosalicylates, 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 cases of salicylate intoxication can result in significant electrolyte and blood pH imbalances, potentially leading to damage of vital organs, including the kidneys and liver. It is crucial for healthcare providers to recognize these risks and act promptly.

Currently, there is no specific antidote available for mesalamine overdose. However, conventional treatment strategies for salicylate toxicity may be beneficial in managing acute overdosage. Initial management should focus on gastrointestinal decontamination to prevent further absorption of the drug. This may involve the use of activated charcoal, provided that the patient presents within an appropriate time frame post-ingestion.

Additionally, it is essential to correct any fluid and electrolyte imbalances that may arise due to the overdose. This can be achieved through the administration of appropriate intravenous fluids and electrolytes, ensuring the maintenance of adequate renal function throughout the treatment process.

It is important to note that mesalamine extended-release capsules are a pH-dependent delayed-release formulation. This characteristic should be taken into account when devising a treatment plan for suspected overdose cases, as it may influence the pharmacokinetics and overall management of the patient.

Nonclinical Toxicology

Dietary mesalamine was not found to be carcinogenic in rats at doses as high as 480 mg/kg/day, nor in mice at 2000 mg/kg/day. 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 (30 mg/kg based on a 50 kg body weight or 1110 mg/m²), respectively, when adjusted for body surface area.

In mutagenicity studies, mesalamine demonstrated negative results in 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. Furthermore, no adverse effects on fertility or reproductive performance were observed in male and female rats administered oral mesalamine doses 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 noted, with single oral doses of 800 mg/kg (approximately 2.2 times the recommended human dose based on body surface area) and 1800 mg/kg (approximately 9.7 times the recommended human dose based on body surface area) resulting in gastrointestinal and renal toxicity in mice and rats, respectively.

Oral administration of mesalamine at doses of 40 mg/kg/day (about 0.20 times the human dose based on body surface area) led to minimal to slight tubular injury. Doses of 160 mg/kg/day (approximately 0.90 times the human dose based on body surface area) or higher in rats resulted in renal lesions, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, oral doses of 60 mg/kg/day (about 1.1 times the human dose based on body surface area) or higher in dogs also caused 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 data.

Patient Counseling

Healthcare providers should advise patients to swallow the mesalamine extended-release capsules whole, emphasizing that they should not cut, break, crush, or chew the capsules to ensure proper medication delivery and effectiveness.

Patients should be informed about the importance of avoiding the co-administration of mesalamine extended-release capsules with antacids, as this may interfere with the medication's action.

It is essential to encourage patients to drink an adequate amount of fluids while taking this medication, as proper hydration can support overall health and medication efficacy.

Additionally, healthcare providers should communicate that mesalamine extended-release capsules can be taken without regard to meals, providing flexibility in the patient's medication schedule.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20° to 25°C (68° to 77°F). Temporary excursions are permissible between 15° and 30°C (59° and 86°F), in accordance with USP Controlled Room Temperature guidelines. 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 AvPAK. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)