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 and methyl methacrylate copolymer (1:2), and methacrylic acid and methyl methacrylate copolymer (1:1). The inner coat consists of an acrylic-based resin, methacrylic acid and methyl methacrylate copolymer (1:2), which dissolves at a pH of 7 or greater, facilitating the release of mesalamine in the terminal ileum and beyond for 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, a molecular weight of 153.1, and a molecular formula of C₇H₇NO₃. Inactive ingredients in each tablet include colloidal silicon dioxide, dibutyl sebacate, FD&C Red #40/Allura Red AC Aluminum Lake, FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake, iron oxide red, lactose monohydrate, magnesium stearate, methacrylic acid and methyl methacrylate copolymer (1:1), methacrylic acid and methyl methacrylate copolymer (1:2), polyethylene glycol 3350, polyethylene glycol 6000, polyvinyl alcohol, povidone K-30, sodium starch glycolate (type A), talc, and titanium dioxide. The imprinting white ink contains isopropyl alcohol, n-butyl alcohol, 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 include the lack of established safety and effectiveness of mesalamine delayed-release tablets beyond 6 weeks of treatment. There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

Healthcare professionals are advised to administer mesalamine delayed-release tablets with careful consideration of the following guidelines. Prior to initiation, it is essential to evaluate the patient's renal function to ensure safety and efficacy.

For the treatment of moderately active ulcerative colitis, the recommended dosage is 1,600 mg, which corresponds to two 800 mg tablets, taken three times daily for a duration of 6 weeks. It is crucial that the tablets are taken on an empty stomach, specifically at least 1 hour before and 2 hours after a meal, to optimize absorption.

Patients should be instructed to swallow the tablets whole without cutting, breaking, or chewing them, as this may affect the delayed-release mechanism. Additionally, it is important to ensure that patients drink an adequate amount of fluids while taking this medication.

It is imperative to note that one mesalamine delayed-release 800 mg tablet 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 at the initiation of 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. If there is any deterioration in renal function, mesalamine delayed-release should be discontinued.

Healthcare professionals should be vigilant for symptoms indicative of mesalamine-induced Acute Intolerance Syndrome, which may mimic an exacerbation of ulcerative colitis. Monitoring for worsening symptoms is crucial, and if acute intolerance syndrome is suspected, discontinuation of the medication is warranted.

Hypersensitivity reactions, including but not limited to myocarditis and pericarditis, require immediate evaluation. Should a hypersensitivity reaction be suspected, mesalamine should be discontinued without delay. 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.

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

The potential for nephrolithiasis should be considered, as mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). It is imperative to ensure adequate hydration during treatment to reduce this risk. Furthermore, healthcare providers should take into account the iron content of mesalamine delayed-release tablets, particularly in patients who are receiving iron supplementation or are at risk for iron overload.

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. No specific laboratory tests are required for the safe use of mesalamine beyond this consideration.

In summary, healthcare professionals should remain alert to the aforementioned warnings and precautions to ensure the safe administration of mesalamine and to monitor patients effectively throughout their treatment.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most 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 warrant careful monitoring. Renal impairment is a significant concern; renal function should be assessed at the beginning of treatment and periodically thereafter. It is essential to evaluate the risks and benefits in patients with known renal impairment or those taking nephrotoxic drugs, and to discontinue mesalamine delayed-release if renal function deteriorates.

Mesalamine-induced Acute Intolerance Syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Therefore, monitoring for worsening symptoms is crucial, and discontinuation of treatment should occur if acute intolerance syndrome is suspected. Hypersensitivity reactions, which may include myocarditis and pericarditis, require 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, necessitating a careful assessment of risks and benefits. Additionally, severe cutaneous adverse reactions can occur; treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity, with further evaluation considered.

Patients should also be advised about photosensitivity, particularly those with pre-existing skin conditions, to avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors. Nephrolithiasis has been noted as a potential risk, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to mitigate this risk.

It is important to consider the iron content of mesalamine delayed-release tablets in patients who are taking iron supplementation or are at risk of iron overload. Furthermore, the use of mesalamine may interfere with laboratory tests, leading to spuriously elevated results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection.

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 result in electrolyte and blood pH imbalances, potentially leading to involvement of 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 recommended to monitor renal function closely and observe for any mesalamine-related adverse reactions in patients receiving these agents.

Additionally, the use of azathioprine or 6-mercaptopurine in conjunction with this medication may elevate the 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.

Due to 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 at oral doses up to 480 mg/kg/day, which correspond to approximately 0.97 times (rat) and 1.95 times (rabbit) the recommended human dose of 4.8 grams per day, based on body surface area. These studies did not demonstrate any evidence of fetal harm.

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; however, 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 its use in pregnant patients.

Lactation

Limited published data on mesalamine use in nursing mothers are insufficient to inform a drug-associated risk. There is a potential for excretion of mesalamine in human breast milk. Caution should be exercised when mesalamine is administered to a nursing woman.

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 of treatment 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 dysfunction 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 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. This can be achieved through the administration of appropriate intravenous fluids, ensuring that renal function is adequately maintained throughout the treatment process.

Given that mesalamine delayed-release is a pH-dependent formulation, this characteristic should be taken into account when devising a treatment plan for suspected overdose cases. Monitoring and supportive care are paramount in managing the patient's condition effectively.

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 up to 480 mg/kg/day in rats and 2,000 mg/kg/day in mice. These doses 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, which is about 0.97 times the recommended human treatment dose based on body surface area, did not adversely affect the fertility or reproductive performance of male and female rats.

Animal studies involving rats, mice, and dogs identified the kidney as the primary organ affected by toxicity. Mesalamine was associated with renal papillary necrosis in rats at single doses ranging from approximately 750 mg/kg to 1,000 mg/kg, which is 1.5 to 2.0 times the recommended human dose. Additionally, doses of 170 mg/kg/day and 360 mg/kg/day, approximately 0.3 and 0.73 times the recommended human dose, respectively, administered to rats over six months resulted in various renal pathologies, including papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.

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

Postmarketing Experience

Reports from postmarketing surveillance have indicated the presence of intact, partially intact, and/or tablet shells in the stool of patients. Patients are advised to contact their healthcare provider if this phenomenon occurs repeatedly.

Patient Counseling

Healthcare providers should inform patients that if they are transitioning from a previous oral mesalamine therapy to mesalamine delayed-release tablets, they must discontinue their prior oral mesalamine therapy and adhere strictly to the dosing instructions for mesalamine delayed-release tablets. 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. They must be instructed to swallow the tablets whole, emphasizing that they should not break, cut, or chew the tablets, as the coating is crucial for the delayed-release mechanism.

Additionally, patients should be encouraged to drink an adequate amount of fluids while on this medication. It is essential to inform them that intact, partially intact, and/or tablet shells may be observed in their stool. Patients should be instructed to contact their healthcare provider if this occurrence happens repeatedly.

Lastly, healthcare providers should advise patients to protect mesalamine delayed-release tablets from moisture to ensure the integrity of the medication.

Storage and Handling

The product is available in tablet form and should be protected from moisture. Tablets can be dispensed without desiccant for a maximum of six weeks.

For optimal storage, the product must be kept at a controlled room temperature ranging from 20° to 25°C (68° to 77°F). Temporary excursions in temperature are permissible between 15° to 30°C (59° to 86°F).

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 Teva Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)