Mesalamine

Description

Each mesalamine delayed-release tablet, USP for oral administration contains 800 mg of mesalamine, USP, an aminosalicylate. The tablets feature an outer protective coat composed of a combination of acrylic-based resins, methacrylic acid copolymer type A, and methacrylic acid copolymer type B. The inner coat is made of an acrylic-based resin, Eudragit S, which dissolves at a pH of 7 or greater, facilitating the release of mesalamine, USP in the terminal ileum and beyond, thereby providing topical anti-inflammatory action in the colon.

Mesalamine, USP, also known as 5-aminosalicylic acid or 5-ASA, has the chemical name 5-amino-2-hydroxybenzoic acid. The structural formula is as follows:

Inactive ingredients in each tablet include colloidal silicon dioxide, dibutyl sebacate, hypromellose, iron oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate, methacrylic acid copolymer type A, methacrylic acid copolymer type B, polyethylene glycol, povidone, sodium starch glycolate, and talc. The black imprinting ink is composed of ammonium hydroxide, iron oxide black, propylene glycol, and shellac glaze.

Uses and Indications

Mesalamine delayed-release tablets are indicated for the treatment of moderately active ulcerative colitis in adults.

Limitations of Use: The safety and effectiveness of mesalamine delayed-release tablets beyond 6 weeks have not been established.

Dosage and Administration

Healthcare professionals should adhere to the following guidelines for the administration of mesalamine delayed-release tablets.

Prior to initiating treatment, it is essential to evaluate the patient's renal function. The recommended dosage for the treatment of moderately active ulcerative colitis is 1,600 mg, administered as two 800 mg tablets taken three times daily for a duration of 6 weeks.

Mesalamine delayed-release tablets should be taken on an empty stomach, specifically at least 1 hour before and 2 hours after a meal. It is crucial that the tablets are swallowed whole; they must not be cut, broken, or chewed. Additionally, patients should be advised to drink an adequate amount of fluids during the course of treatment.

It is important to note that one mesalamine delayed-release tablet of 800 mg should not be substituted for two mesalamine delayed-release 400 mg oral products, as this may lead to dosing inaccuracies.

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 prior to initiating treatment with mesalamine and monitored periodically throughout the course of therapy. In patients with known renal impairment or those taking nephrotoxic medications, a careful evaluation of the risks and benefits is essential. Should renal function deteriorate, mesalamine delayed-release must be discontinued (5.1, 7.1, 8.6).

Healthcare professionals should be vigilant for mesalamine-induced acute intolerance syndrome, as its symptoms may closely resemble an exacerbation of ulcerative colitis. Monitoring for any worsening of symptoms is crucial, and if acute intolerance syndrome is suspected, discontinuation of the medication is warranted (5.2).

Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, mesalamine should be discontinued promptly (5.3). Additionally, in patients with known liver impairment, a thorough assessment of the risks and benefits of continuing treatment is necessary due to the potential for hepatic failure (5.4).

Severe cutaneous adverse reactions necessitate immediate discontinuation of mesalamine at the first signs or symptoms, along with consideration for further evaluation (5.5). 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 (5.6).

The formation of nephrolithiasis is a potential risk associated with mesalamine, as mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is essential to minimize this risk (5.7). Furthermore, healthcare providers should consider the iron content of mesalamine delayed-release in patients who are on iron supplementation or those at risk of iron overload (5.8).

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 via liquid chromatography with electrochemical detection (5.9). Regular assessment of renal function and awareness of potential laboratory test interferences are critical components of patient management during mesalamine therapy.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in 2% or more of participants, include headache, nausea, nasopharyngitis, abdominal pain, and worsening of ulcerative colitis.

Serious adverse reactions have been reported and require careful monitoring. Renal impairment is a significant concern; renal function should be assessed at the beginning of treatment and periodically thereafter. Mesalamine delayed-release should be discontinued if renal function deteriorates. Additionally, 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, necessitate immediate evaluation and discontinuation of the medication if such reactions are suspected. Hepatic failure is another serious risk, particularly in patients with known liver impairment, and the risks and benefits should be carefully weighed in these cases. Severe cutaneous adverse reactions require prompt discontinuation at the first signs or symptoms, along with further evaluation for hypersensitivity.

Patients should also be informed about the risk of nephrolithiasis, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to mitigate this risk. Furthermore, the iron content of mesalamine delayed-release should be considered in patients taking iron supplements or those at risk of iron overload.

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.

Symptoms of salicylate toxicity, which may occur, include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication can result in electrolyte and blood pH imbalances, potentially affecting other organs, including the kidneys and liver.

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

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 mesalamine-related adverse reactions in patients receiving these agents.

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 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

Safety and effectiveness of mesalamine delayed-release have not been established in pediatric patients. Healthcare professionals are advised to refer to the prescribing information for other approved mesalamine products to obtain information regarding their safety and effectiveness in this population.

Geriatric Use

Clinical studies of mesalamine delayed-release did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently than 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 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 therapy with mesalamine delayed-release. Additionally, when prescribing this medication 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 delayed-release in this population.

Pregnancy

Limited published data on mesalamine use in pregnant patients are insufficient to inform a drug-associated risk. Animal reproduction studies have been conducted in rats and rabbits during organogenesis, with oral doses up to 480 mg/kg/day. These studies did not demonstrate any evidence of fetal harm, with doses approximately 0.97 times the recommended human dose in rats and 1.95 times in rabbits, based on body surface area.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20%, respectively, although the background risk for the indicated populations remains unknown. Given the limited data available, healthcare professionals should weigh the potential benefits of mesalamine against any unknown risks when considering treatment in pregnant patients.

Lactation

There is no specific information available regarding the use of mesalamine in lactating mothers or its effects on breast milk. Additionally, there are no data on the excretion of mesalamine in human 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

Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically during treatment. It is important to evaluate the risks and benefits in patients with known renal impairment or those taking nephrotoxic drugs, with close monitoring of renal function. If there is any deterioration in renal function, mesalamine delayed-release should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of treatment. It is essential to consider the degree of liver function compromise when determining the appropriateness of therapy. Monitoring of liver function is recommended to ensure patient safety and to adjust treatment as necessary. Specific dosage adjustments may be required based on the severity of hepatic impairment, and healthcare providers should remain vigilant in assessing any potential adverse effects related to compromised liver function.

Overdosage

In the event of an overdose of mesalamine delayed-release, which is classified as an aminosalicylate, 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, with the potential for involvement of other organs, including renal and hepatic systems. It is crucial to recognize these complications early to mitigate further risks.

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

In addition to decontamination, it is essential to correct any fluid and electrolyte imbalances that may arise. This can be achieved through the administration of appropriate intravenous fluids, ensuring that renal function is adequately maintained throughout the treatment process.

It is important to note that mesalamine delayed-release tablets are pH dependent. This characteristic should be taken into account when formulating a treatment plan for suspected overdose, as it may influence the drug's absorption and the overall management strategy.

Nonclinical Toxicology

Dietary mesalamine was evaluated for its carcinogenic potential in both rats and mice. The results indicated that mesalamine was not carcinogenic at doses as high as 480 mg/kg/day in rats and 2,000 mg/kg/day in mice, which correspond to approximately 0.97 and 2.0 times the recommended human dose of 4.8 grams per day based on body surface area.

In terms of genotoxicity, mesalamine demonstrated no genotoxic effects in several assays, including the Ames test, the Chinese hamster ovary cell chromosomal aberration assay, and the mouse micronucleus test. Furthermore, oral administration of mesalamine at doses up to 480 mg/kg/day, approximately 0.97 times the recommended human treatment dose based on body surface area, did not adversely affect fertility or reproductive performance in male and female rats.

Animal studies have identified the kidney as the principal organ affected by mesalamine toxicity. In rats, renal papillary necrosis was observed following single doses of approximately 750 mg/kg to 1,000 mg/kg, which is 1.5 to 2.0 times the recommended human dose. Chronic administration of doses of 170 mg/kg/day and 360 mg/kg/day, approximately 0.3 and 0.73 times the recommended human dose, respectively, for six months resulted in significant renal pathology, including papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.

In mice, administration of oral doses of 4,000 mg/kg/day, approximately 4.1 times the recommended human dose, for three months led to tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis. In dogs, single doses of 6,000 mg, approximately 6.25 times the recommended human dose of delayed-release mesalamine tablets, resulted in renal papillary necrosis, although these doses were not fatal. Chronic administration of mesalamine at doses of 80 mg/kg/day, which is 0.5 times the recommended human dose, also resulted in renal changes in dogs.

Postmarketing Experience

No postmarketing experience details are available in the provided data.

Patient Counseling

Healthcare providers should inform patients that if they are transitioning from a previous oral mesalamine therapy to mesalamine delayed-release, they must discontinue their prior oral mesalamine therapy and adhere strictly to the dosing instructions for mesalamine delayed-release. It is important to clarify that one mesalamine delayed-release 800 mg tablet is not interchangeable with two mesalamine delayed-release 400 mg oral products.

Patients should be advised to take mesalamine delayed-release tablets on an empty stomach, specifically at least one hour before and two hours after a meal. It is crucial to instruct patients to swallow the tablets whole, emphasizing that they should not break, cut, or chew the tablets, as the coating is essential for the delayed-release mechanism.

Healthcare providers should encourage patients to maintain adequate hydration by drinking sufficient fluids. Additionally, patients should be made aware that intact, partially intact, and/or tablet shells may be observed in their stool. If this occurrence happens repeatedly, patients should be instructed to contact their healthcare provider for further guidance.

Lastly, it is important to advise patients to protect mesalamine delayed-release tablets from moisture to ensure their efficacy.

Storage and Handling

Tablets are supplied in a configuration that allows for dispensing without desiccant for a duration of up to 6 weeks. It is essential to protect the tablets from moisture to maintain their integrity.

For optimal storage, the tablets should be kept at a temperature range of 20° to 25° C (68° to 77° F). Temporary excursions are permissible between 15° to 30° C (59° to 86° F), in accordance with USP Controlled Room Temperature guidelines. Proper handling and storage conditions are crucial to ensure the product's efficacy and safety.

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 Amneal Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)