Mesalamine

Description

Each mesalamine extended-release capsule is a delayed- and extended-release dosage form intended for oral administration. 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 formulation includes granules of mesalamine embedded in a polymer matrix, featuring an enteric coating that dissolves at a pH of 6 and above.

Inactive ingredients in the mesalamine extended-release capsules comprise anhydrous citric acid, aspartame, colloidal silicon dioxide, edible black ink, hypromellose, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, povidone, simethicone emulsion, ethyl acrylate/methyl methacrylate copolymer, talc, titanium dioxide, triethyl citrate, and vanilla flavor. Each capsule also contains 0.56 mg of phenylalanine.

Uses and Indications

Mesalamine 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 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, discontinuation of mesalamine is warranted.

Healthcare professionals should be vigilant for symptoms indicative of mesalamine-induced acute intolerance syndrome, which may mimic an exacerbation of ulcerative colitis. Close monitoring for worsening symptoms is advised, 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, mesalamine should be discontinued promptly. 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, treatment should be stopped at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation may be necessary in these cases. Patients should also be informed about the risk of photosensitivity. Those with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors.

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

For patients with phenylketonuria (PKU), it is important to note that mesalamine contains phenylalanine. Prior to prescribing mesalamine extended-release capsules, healthcare providers should consider the total daily intake of phenylalanine from all sources.

General precautions include the potential for interference with laboratory tests. Specifically, the use of mesalamine may result in spuriously elevated results when measuring urinary normetanephrine using liquid chromatography with electrochemical detection. Regular monitoring of renal function is recommended throughout the treatment period to ensure patient safety.

Side Effects

Patients may experience a range of adverse reactions while receiving 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 have been reported, necessitating careful monitoring and management. Renal function should be assessed at the beginning of treatment and periodically thereafter, with discontinuation of therapy if renal function deteriorates. Additionally, mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis; therefore, it is crucial to monitor for worsening symptoms and discontinue treatment if this syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of the medication if such reactions are suspected. Patients with known liver impairment should be evaluated for the risks and benefits of treatment, as hepatic failure has been noted in this population.

Severe cutaneous adverse reactions have been observed, and treatment should be discontinued at the first signs or symptoms of these reactions or any other signs of hypersensitivity. Patients are also advised to avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors due to the risk of photosensitivity.

Nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). To mitigate this risk, it is important to ensure adequate fluid intake during treatment. Furthermore, caution is advised in patients with phenylketonuria (PKU), as mesalamine extended-release capsules contain phenylalanine. The combined daily amount of phenylalanine from all sources should be considered before prescribing.

The use of mesalamine may interfere with laboratory tests, leading to spuriously elevated results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection.

Additional adverse reactions may include symptoms of salicylate toxicity, which can manifest as nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication may result in electrolyte and blood pH imbalances, potentially leading to damage to 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.

When azathioprine or 6-mercaptopurine is administered alongside this medication, there is an elevated 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 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 needed 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. Careful assessment and monitoring are recommended to ensure the safety and efficacy of mesalamine extended-release capsules in this population.

Pregnancy

Published data from meta-analyses, cohort studies, and case series regarding the use of mesalamine during pregnancy have not consistently demonstrated an association with 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 indicate 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 2500 g), and small for gestational age infants at birth.

While there is no clear evidence that mesalamine exposure during early pregnancy is linked to an increased risk of major congenital malformations, including cardiac malformations, the interpretation of existing epidemiologic studies is complicated by methodological limitations. These limitations include the inability to control for confounding factors such as underlying maternal disease and concomitant medication use, as well as gaps in information regarding the dose and duration of mesalamine use.

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

Lactation

Data from published literature indicate that mesalamine and its metabolite, N-acetyl 5-aminosalicylic acid, are present in human milk in small amounts, with relative infant doses (RID) of 2% or less. The average concentration of mesalamine in milk ranges from non-detectable to 0.5 mg/L, while the average concentration of N-acetyl-5-aminosalicylic acid in milk ranges from 0.2 to 9.3 mg/L. Based on these concentrations, estimated daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day (RID 0 to 0.1%) for mesalamine and 0.03 to 1.4 mg/kg/day for N-acetyl-5-aminosalicylic acid.

There have been case reports of diarrhea in breastfed infants exposed to mesalamine. However, there is no information available regarding the effects of mesalamine on milk production. The lack of clinical data during lactation prevents a clear determination of the risk of mesalamine extended-release capsules to an infant during breastfeeding. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for mesalamine extended-release capsules and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Healthcare providers should advise caregivers to monitor breastfed infants for signs of diarrhea.

Renal Impairment

Renal function should be assessed at the beginning of treatment and periodically throughout the course of therapy in patients with renal impairment. It is essential to evaluate the risks and benefits of treatment in these patients, particularly those who are also taking nephrotoxic drugs, and to monitor renal function closely. If there is any deterioration in renal function, discontinuation of treatment is recommended.

Additionally, ensuring adequate fluid intake during treatment is crucial to prevent nephrolithiasis, as mesalamine-containing stones may not be detectable by standard radiography or computed tomography (CT).

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of treatment. It is essential to assess liver function prior to initiating therapy and to monitor liver parameters throughout the course of treatment. Adjustments to dosage may be necessary based on the severity of liver impairment, and close monitoring is recommended to ensure patient safety and therapeutic efficacy.

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, which may lead to damage of vital organs, particularly the kidneys and liver.

There is currently no specific antidote for mesalamine overdose. However, conventional treatment strategies for salicylate toxicity may be employed effectively in cases of acute overdosage. Initial management should focus on gastrointestinal decontamination to prevent further absorption of the drug.

It is crucial to address any fluid and electrolyte imbalances that may arise, which can be achieved through the administration of appropriate intravenous therapy. Maintaining adequate renal function is also a key component of the management strategy.

Additionally, it is important to note that mesalamine extended-release capsules are designed as a pH-dependent delayed-release formulation. This characteristic should be taken into account when treating a suspected overdose, as it may influence the timing and effectiveness of therapeutic interventions.

Nonclinical Toxicology

Dietary mesalamine was evaluated for carcinogenic potential in both rats and mice. In these studies, mesalamine did not demonstrate carcinogenicity at doses of up to 480 mg/kg/day in rats and 2,000 mg/kg/day in mice. These doses correspond to approximately 2.6 and 5.4 times the recommended human dose of granulated mesalamine capsules, which is 1.5 g/day, based on body surface area.

In terms of mutagenicity, mesalamine was found to be negative 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.

Regarding reproductive toxicity, no adverse effects on fertility or reproductive performance were observed in male and female rats administered oral doses of mesalamine 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 toxicology 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 in mice and 1,800 mg/kg in rats, which are approximately 2.2 and 9.7 times the recommended human dose, respectively, based on body surface area. These high doses resulted in gastrointestinal and renal toxicity.

At lower oral doses of 40 mg/kg/day, which is about 0.20 times the human dose based on body surface area, minimal to slight tubular injury was noted. Doses of 160 mg/kg/day or higher, approximately 0.90 times the human dose, led to renal lesions in rats, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, in dogs, oral doses of 60 mg/kg/day or higher, about 1.1 times the human dose based on body surface area, 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. Hypersensitivity reactions, including angioedema and anaphylaxis, have been documented. Additionally, cases of renal impairment, such as acute interstitial nephritis, have been reported. There have also been instances of liver enzyme elevations and hepatotoxicity. Rare occurrences of myocarditis and pericarditis have been observed. Furthermore, pulmonary adverse reactions, including eosinophilic pneumonia, have been noted. Other reported adverse reactions include skin reactions such as rash, pruritus, and urticaria.

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 avoid the 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 to ensure proper hydration. Additionally, mesalamine extended-release capsules can be taken without regard to meals, providing flexibility in the patient's dosing schedule.

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. If patients observe discolored urine, they should be instructed 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 (e.g., in the toilet).

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a temperature range of 20° to 25°C (68° to 77°F). Temporary excursions are permitted between 15° and 30°C (59° and 86°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

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

View full prescribing information (PDF)