Mesalamine

Description

Each mesalamine delayed-release tablet, USP for oral administration contains 800 mg of mesalamine, USP, an aminosalicylate. Mesalamine, USP, also known as 5-aminosalicylic acid or 5-ASA, has the chemical name 5-amino-2-hydroxybenzoic acid. The molecular weight of mesalamine is 153.1, and its molecular formula is 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.

Uses and Indications

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

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 initiating treatment, 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 meals, 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 encourage patients to drink an adequate amount of fluids during the course of treatment to maintain hydration.

Healthcare professionals should not substitute one mesalamine delayed-release 800 mg tablet 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. Should renal function deteriorate, mesalamine delayed-release must 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 any worsening of symptoms is crucial, and discontinuation of the medication is warranted if acute intolerance syndrome is suspected.

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

In patients with pre-existing liver impairment, a thorough assessment of the risks and benefits of mesalamine therapy is necessary due to the potential for hepatic failure.

Severe cutaneous adverse reactions may occur; therefore, it is imperative to discontinue mesalamine at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation should be considered 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 formation of nephrolithiasis has been associated with mesalamine, as mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to reduce this risk.

Healthcare providers should also consider the iron content of mesalamine delayed-release tablets in patients who are receiving iron supplementation or those at risk of 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 using liquid chromatography with electrochemical detection.

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 immediate attention. 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 evaluated. Severe cutaneous adverse reactions require discontinuation at the first signs or symptoms, along with consideration for further evaluation. Patients should also be advised about photosensitivity; those with pre-existing skin conditions should avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors. Nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to mitigate this risk.

Additional considerations include the iron content of mesalamine delayed-release tablets, which should be taken into account for patients on iron supplementation or those 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 occur, including 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

There are currently no documented drug interactions associated with 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

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 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

There is no specific information available regarding the use of this medication in nursing mothers or its effects on lactation. Consequently, the potential for excretion in breast milk and the impact on breastfed infants remain undetermined. Healthcare professionals should exercise caution and consider the benefits and risks when prescribing this medication to lactating mothers.

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. In cases where renal function deteriorates, 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 liver function during the course of treatment.

Overdosage

In cases of salicylate overdose, a range of symptoms may manifest, including nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, headache, dizziness, confusion, and seizures. These symptoms can indicate the severity of salicylate toxicity and require prompt medical attention.

Severe intoxication with salicylates can lead to significant complications, including electrolyte imbalances and alterations in blood pH. Additionally, there is a risk of renal and liver involvement, which necessitates careful monitoring and management.

Currently, there is no specific antidote available for mesalamine overdose. However, conventional therapies used for salicylate toxicity may provide some benefit in managing the condition. In cases of acute overdosage, gastrointestinal tract decontamination may be warranted to prevent further absorption of the drug.

Management of salicylate overdose should include the correction of fluid and electrolyte imbalances through appropriate intravenous therapy. It is also crucial to maintain adequate renal function during the treatment process to mitigate potential complications associated with overdose.

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 of 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 fertility or reproductive performance in male and female rats.

Animal studies involving rats, mice, and dogs identified the kidney as the primary organ affected by mesalamine toxicity. In rats, single doses ranging from approximately 750 mg/kg to 1,000 mg/kg, equating to 1.5 to 2.0 times the recommended human dose, resulted in renal papillary necrosis. Additionally, 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, over a six-month period led to renal pathologies including papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.

In mice, oral doses of 4,000 mg/kg/day, about 4.1 times the recommended human dose, administered for three months resulted in tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis. 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

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

Patient Counseling

Patients should be informed 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 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 instructed to take mesalamine delayed-release tablets on an empty stomach, specifically at least one hour before and two hours after a meal. They must swallow the tablets whole and should not break, cut, or chew them, as the coating is essential for the delayed-release formulation. Additionally, patients should be advised to maintain adequate fluid intake.

Patients should be made aware that intact, partially intact, and/or tablet shells may be observed in their stool. If this occurs repeatedly, they should contact their healthcare provider. It is also crucial to instruct patients to protect mesalamine delayed-release tablets from moisture.

Patients should be informed that mesalamine delayed-release tablets may potentially decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic drugs, including NSAIDs. Periodic monitoring of renal function will be conducted during therapy, and patients should be advised to complete all blood tests ordered by their healthcare provider.

Healthcare providers should inform patients about the signs and symptoms of hypersensitivity reactions. Patients must be instructed to discontinue mesalamine delayed-release tablets and 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, malaise, conjunctivitis, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, it is important to communicate the signs and symptoms of worsening liver function and advise them to report any such signs or symptoms to their healthcare provider. Patients should also be informed about the signs and symptoms of severe cutaneous adverse reactions and instructed to stop taking mesalamine delayed-release tablets and report to their healthcare provider at the first appearance of such reactions or any other signs of hypersensitivity.

Patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. They should also be instructed to maintain adequate fluid intake 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.

Patients should inform their healthcare provider if they are taking iron-containing supplements. 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 during therapy. They should be advised to complete all blood tests ordered by their healthcare provider.

Lastly, patients should be informed that their urine may become discolored reddish-brown while taking mesalamine delayed-release tablets when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. If discolored urine is observed, patients should be advised to monitor their urine flow and report to their healthcare provider only if the urine is discolored upon leaving the body, prior to contact with any surface or water.

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 6 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

The use of mesalamine delayed-release may result in spuriously elevated urinary normetanephrine test results due to the similarity in chromatograms between normetanephrine and mesalamine's main metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Clinicians are advised to consider alternative, selective assays for accurate measurement of normetanephrine.

Patients should be counseled to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors to minimize the risk of photosensitivity reactions.

FDA Insert (PDF)

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

View full prescribing information (PDF)