Mesalamine

Description

Each mesalamine delayed-release tablet for oral administration contains 800 mg of mesalamine USP, an aminosalicylate with the chemical name 5-amino-2-hydroxybenzoic acid. Mesalamine appears as light tan to pink colored, needle-shaped crystals, which may darken upon exposure to air. The compound is odorless or may exhibit a slight characteristic odor. It is slightly soluble in water and very slightly soluble in methanol, dehydrated alcohol, and acetone, while being practically insoluble in n-butyl alcohol, chloroform, ether, ethyl acetate, n-hexane, methylene chloride, and n-propyl alcohol. Mesalamine is soluble in dilute hydrochloric acid and dilute alkali hydroxides.

The delayed-release tablets feature a single-layered coating composed of an acrylic-based resin, Eudragit S (methacrylic acid copolymer B, NF), which dissolves at a pH of 7 or greater, facilitating the release of mesalamine for topical anti-inflammatory action in the colon. Each tablet also contains the following inactive ingredients: acetyltributyl citrate, colloidal silicone dioxide, ferric oxide red, magnesium stearate, methacrylic acid copolymer type B, microcrystalline cellulose, povidone, sodium starch glycolate, talc, and titanium dioxide. The tablet is printed with opacode black S-1-17823, which includes ammonium hydroxide, butyl alcohol, ferrosoferric oxide, isopropyl alcohol, propylene glycol, and shellac.

Uses and Indications

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

Safety and effectiveness of mesalamine delayed-release tablets beyond 6 weeks have not been established. There are no teratogenic or nonteratogenic effects associated with this medication.

Dosage and Administration

Healthcare professionals should adhere to the following guidelines for the administration of mesalamine delayed-release tablets, 800 mg.

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 1600 mg, which corresponds to two 800 mg tablets, administered 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 meals. 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 to ensure proper hydration during the course of treatment.

It is important to note that one mesalamine delayed-release tablet, 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, aminosalicylates, or any of the components of the formulation.

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 should be discontinued.

Healthcare professionals should be vigilant for signs of mesalamine-induced Acute Intolerance Syndrome, as symptoms may closely resemble an exacerbation of ulcerative colitis. If acute intolerance syndrome is suspected, mesalamine should be discontinued immediately.

Hypersensitivity reactions, which may include serious conditions such as myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, mesalamine should be discontinued without delay.

In patients with known 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 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 warranted in these cases.

Patients should be advised to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors, particularly if they have preexisting skin conditions, due to the risk of photosensitivity associated with mesalamine.

Nephrolithiasis is a potential risk, as mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). It is crucial to ensure adequate hydration during treatment to mitigate this risk.

Additionally, healthcare professionals should be aware 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 monitoring of renal function is recommended at the beginning of treatment and periodically thereafter to ensure patient safety and effective management of therapy.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in 2% or more of patients, 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 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 mesalamine should be discontinued if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, necessitate immediate evaluation and discontinuation of treatment if such reactions are suspected. Hepatic failure is another serious risk, particularly in patients with known liver impairment, and the risks and benefits of treatment should be carefully evaluated in these individuals. Severe cutaneous adverse reactions may occur; treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity, with further evaluation considered.

Photosensitivity is a noted concern, and patients with preexisting skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. Nephrolithiasis has also 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.

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.

Patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any of the ingredients of mesalamine delayed-release tablets, should not receive this treatment. Symptoms of salicylate toxicity, which may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures, should be monitored closely. Severe salicylate intoxication can lead to electrolyte and blood pH imbalances, potentially affecting 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 advisable 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 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

Safety and effectiveness of mesalamine in pediatric patients have not been established. Healthcare professionals are advised to refer to the prescribing information for other approved mesalamine products to obtain information regarding the safety and effectiveness of these alternatives in pediatric populations.

Geriatric Use

Clinical studies of mesalamine delayed-release tablets 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, such as mesalamine delayed-release tablets at a dosage of 800 mg.

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 tablets. 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 therapy 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 treatment in pregnant patients.

Lactation

There is no specific information available regarding the use of mesalamine in lactating mothers. Additionally, there is no data on the potential for excretion of mesalamine in breast milk or any associated risks to 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 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. In cases where renal function deteriorates, mesalamine 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.

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, as well as potential involvement of other organs, notably the kidneys and liver. Given the absence of a specific antidote for mesalamine overdose, management should focus on conventional therapies for salicylate toxicity.

Initial management may involve gastrointestinal tract decontamination to minimize further absorption of the drug. This can be achieved through methods such as activated charcoal, provided that the patient presents within an appropriate time frame post-ingestion.

It is crucial to address any fluid and electrolyte imbalances that may arise. This can be accomplished through the administration of appropriate intravenous fluids, which will also help maintain adequate renal function during the management of the overdose.

Additionally, it is important to consider that mesalamine is 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 timing and effectiveness of therapeutic interventions.

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 2000 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 of mesalamine delayed-release tablets, 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 doses of mesalamine 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 have identified the kidney as the principal organ affected by mesalamine toxicity. In rats, single doses ranging from approximately 750 mg/kg to 1000 mg/kg, which are 1.5 to 2.0 times the recommended human dose, resulted in renal papillary necrosis. 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 over six months, led to renal pathologies including papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.

In mice, oral administration of 4000 mg/kg/day for three months, approximately 4.1 times the recommended human dose, resulted in tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis. In dogs, a single dose of 6000 mg of delayed-release mesalamine tablets, about 6.25 times the recommended human dose, 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

Postmarketing experience has identified the occurrence of intact, partially intact, and/or tablet shells in the stool of patients. It is advised that patients 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, it is essential to discontinue the prior oral mesalamine therapy and adhere to the dosing instructions for the mesalamine delayed-release tablets.

Patients should be made aware that one mesalamine delayed-release tablet of 800 mg is not interchangeable with two mesalamine delayed-release 400 mg oral products. It is important to emphasize that mesalamine delayed-release tablets should be taken on an empty stomach, specifically at least one hour before and two hours after a meal.

Healthcare providers should instruct patients to swallow the mesalamine delayed-release tablets whole, advising against breaking, cutting, or chewing the tablets, as the coating is a critical component of the delayed-release formulation. Patients should also be encouraged to drink an adequate amount of fluids while taking this medication.

Additionally, patients should be informed that intact, partially intact, and/or tablet shells may be observed in their stool. They should be advised to contact their healthcare provider if this occurrence happens repeatedly. Lastly, it is crucial to instruct patients to protect mesalamine delayed-release tablets from moisture to ensure their effectiveness.

Storage and Handling

The product is supplied in a configuration that allows for optimal storage and handling. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

To ensure the integrity of the tablets, they must be protected from moisture. It is important to note that the tablets can be dispensed without a desiccant for a maximum duration of 6 weeks. Proper adherence to these storage conditions will help maintain 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 Zydus Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)