Mesalamine

Description

Each mesalamine extended-release capsule is designed for oral administration and serves as a delayed-and extended-release dosage form. 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 mesalamine is formulated in granules that are embedded within a polymer matrix, featuring an enteric coating that dissolves at a pH of 6 and above.

The inactive ingredients in the mesalamine extended-release capsules USP include black iron oxide, colloidal silicon dioxide, edible black ink (comprising shellac), ethyl acrylate and methyl methacrylate copolymer, FD and C Blue # 1, FD and C Red # 3, gelatin, hypromellose, magnesium stearate, methacrylic acid and methyl methacrylate copolymer, microcrystalline cellulose, polyethylene glycol, potassium hydroxide, propylene glycol, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate, and vanillin. It is important to note that the FDA-approved dissolution test specifications differ from the 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. It is essential that the capsules be swallowed whole; they must not be cut, broken, crushed, or chewed to ensure proper release and absorption of the medication. Co-administration with antacids should be avoided to prevent potential interactions. Patients are advised 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. In patients with known renal impairment or those taking nephrotoxic medications, careful evaluation of the risks and benefits is essential. If renal function deteriorates, discontinuation of treatment is warranted.

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 treatment should be discontinued if acute intolerance syndrome is suspected.

Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, treatment should be discontinued without delay. Additionally, in patients with known liver impairment, a thorough assessment of the risks and benefits of continued therapy is necessary due to the potential for hepatic failure.

Severe cutaneous adverse reactions necessitate prompt action; treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation may be required in these cases. Patients should also be advised about the risk of photosensitivity, particularly those with pre-existing skin conditions. It is recommended that they avoid sun exposure, wear protective clothing, and utilize a broad-spectrum sunscreen when outdoors.

The risk of nephrolithiasis should be communicated to patients, as mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). To mitigate this risk, ensuring adequate fluid intake during treatment is essential.

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.

In summary, healthcare professionals must remain vigilant in monitoring renal function, recognizing potential adverse reactions, and advising patients on necessary precautions to ensure safe and effective use of mesalamine.

Side Effects

Patients may experience a range of adverse reactions during treatment. The most common adverse reactions, occurring in 3% or more of participants, include headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis.

Serious adverse reactions warrant careful monitoring and management. Patients should be assessed for renal function at the beginning of treatment and periodically thereafter, particularly those with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates, discontinuation of treatment is advised. Additionally, 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 essential, and treatment should be discontinued if this syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of treatment if suspected. Patients with known liver impairment should be carefully evaluated for the risks and benefits of treatment, as hepatic failure has been reported. Severe cutaneous adverse reactions necessitate discontinuation at the first signs or symptoms, along with consideration for further evaluation.

Patients should also be informed about the risk of nephrolithiasis, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Adequate fluid intake during treatment is crucial to mitigate this risk. Furthermore, patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen to prevent photosensitivity reactions.

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.

Patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or any component of mesalamine extended-release capsules should avoid 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 resulting in damage to other organs, including the kidneys and liver.

Drug Interactions

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

When administered alongside azathioprine or 6-mercaptopurine, 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.

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.

Pregnancy

Published data from meta-analyses, cohort studies, and case series regarding the use of mesalamine during pregnancy have not consistently demonstrated an association between mesalamine and 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 2,500 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 methodological limitations of existing epidemiologic studies, such as the inability to control for confounders like underlying maternal disease and concomitant medication use, complicate the interpretation of these findings.

Healthcare professionals should consider these factors when prescribing mesalamine to pregnant patients and remain vigilant regarding the potential impact of disease activity on pregnancy outcomes.

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. Treatment should be discontinued if there is any deterioration in renal function.

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, it is important to ensure adequate fluid intake during treatment.

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 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. Common manifestations include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and various neurologic symptoms such as headache, dizziness, confusion, and seizures.

Severe cases of salicylate intoxication may 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 promptly.

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, which will also help maintain adequate renal function during the management of the overdose.

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 timing and effectiveness of therapeutic interventions.

Nonclinical Toxicology

Dietary mesalamine has been evaluated for its potential carcinogenic effects in nonclinical studies. In these studies, mesalamine was not found to be carcinogenic in rats at doses as high as 480 mg/kg/day, nor in mice at doses up to 2,000 mg/kg/day. These doses correspond to approximately 2.6 and 5.4 times the recommended human dose of granulated mesalamine capsules of 1.5 g/day, respectively, when adjusted for body surface area.

In terms of mutagenicity, mesalamine demonstrated negative results in several assays, including 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.

Non-teratogenic effects of mesalamine were observed in reproductive studies, where no effects on fertility or reproductive performance were noted in male and female rats at oral doses up to 320 mg/kg, which is approximately 1.7 times the recommended human dose based on body surface area.

Animal studies assessing the pharmacology and toxicity of mesalamine, 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 determined to be 800 mg/kg (approximately 2.2 times the recommended human dose) for mice and 1,800 mg/kg (approximately 9.7 times the recommended human dose) for rats, both of which resulted in gastrointestinal and renal toxicity.

At lower oral doses, renal effects were also noted. Specifically, doses of 40 mg/kg/day (about 0.20 times the human dose) resulted in minimal to slight tubular injury in rats. Higher doses of 160 mg/kg/day (approximately 0.90 times the human dose) or more led to significant renal lesions, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, in dogs, oral doses of 60 mg/kg/day (about 1.1 times the human dose) or higher resulted in renal lesions such as tubular atrophy, interstitial cell infiltration, chronic nephritis, and papillary necrosis.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include pancreatitis, hepatic failure, renal failure, colitis, and allergic reactions, which encompass anaphylaxis. Skin reactions such as rash, pruritus, and urticaria have also been documented. Hematologic reactions, including thrombocytopenia and leukopenia, were reported, as well as respiratory reactions, notably interstitial lung disease.

Furthermore, additional safety updates from postmarketing experience have indicated serious gastrointestinal events, including bowel obstruction and perforation.

Patient Counseling

Healthcare providers should advise patients to swallow mesalamine extended-release capsules whole, without cutting, breaking, crushing, or chewing them. It is important to inform patients to avoid co-administration of these capsules with antacids, as this may affect the medication's efficacy.

Patients should be encouraged to drink an adequate amount of fluids while taking this medication. They can take mesalamine extended-release capsules without regard to meals, providing flexibility in their dosing schedule.

Additionally, healthcare providers should inform patients that their urine may become discolored reddish-brown while using mesalamine extended-release capsules, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. Patients should be instructed to observe their urine flow and to report to their healthcare provider only if they notice discolored urine upon leaving the body, prior to contact with any surface or water, such as in the toilet.

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 container requirements and special handling needs should be adhered to in order to maintain product integrity.

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 Ascend Laboratories, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)