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 the use of this medication as per the available data.

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 to ensure safety and efficacy. The capsules must be swallowed whole; they should not be cut, broken, crushed, or chewed, as this may affect the release mechanism of the medication.

Co-administration with antacids is not advised, as it may interfere with the therapeutic effects of mesalamine. Patients should be encouraged 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.

Mesalamine-Induced Acute Intolerance Syndrome may present with symptoms that are challenging to differentiate from an exacerbation of ulcerative colitis. Healthcare professionals should monitor patients for any worsening of symptoms and discontinue treatment if acute intolerance syndrome is suspected.

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

In patients with known liver impairment, a thorough assessment of the risks and benefits of treatment 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 be advised about the risk of photosensitivity. Those with pre-existing skin conditions should take precautions to avoid sun exposure, including wearing protective clothing and using 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). It is crucial to ensure adequate fluid intake during treatment to mitigate this risk.

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.

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

Regular assessment of renal function is recommended at the beginning of treatment and periodically thereafter, especially in patients with known renal impairment or those on nephrotoxic drugs.

In the event of a suspected hypersensitivity reaction, immediate evaluation is critical, and treatment should be discontinued. Similarly, if acute intolerance syndrome is suspected, or if there are any signs or symptoms of severe cutaneous adverse reactions or other hypersensitivity indications, treatment should be stopped, and further evaluation should be considered.

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 warrant careful monitoring and immediate action. Renal function should be assessed at the beginning of treatment and periodically thereafter, with discontinuation of therapy if renal function deteriorates. Patients should be monitored for symptoms of mesalamine-induced acute intolerance syndrome, which may mimic an exacerbation of ulcerative colitis; treatment should be discontinued if this syndrome is suspected. Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation and discontinuation of the medication if such reactions are suspected.

Severe cutaneous adverse reactions have been reported; therefore, treatment should be stopped at the first signs or symptoms of these reactions or any other signs of hypersensitivity, with further evaluation considered. Patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen to mitigate the risk of photosensitivity.

Nephrolithiasis has been noted as a potential risk, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Patients should be encouraged to maintain adequate fluid intake during treatment. Additionally, caution is advised in patients with known liver impairment due to the risk of hepatic failure; the risks and benefits should be carefully evaluated in these individuals.

For patients with phenylketonuria (PKU), it is important to consider the combined daily amount of phenylalanine from all sources, including mesalamine extended-release capsules, before prescribing. 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.

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), with this medication may lead to an increased risk of nephrotoxicity. It is advisable to monitor renal function closely and observe for any mesalamine-related adverse reactions during co-administration.

When used in conjunction with azathioprine or 6-mercaptopurine, 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.

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 should be exercised when considering the use of this medication in children and adolescents. Further studies are needed to determine appropriate dosing and 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 advised 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 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 2500 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 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 or women of childbearing potential.

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 breast milk ranges from non-detectable to 0.5 mg/L, while the average concentration of N-acetyl-5-aminosalicylic acid 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.

Caregivers should be advised to monitor breastfed infants for signs of diarrhea.

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. If there is any deterioration in renal function, discontinuation of treatment is recommended.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits associated with 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.

Currently, there is no specific antidote available for mesalamine overdose. However, conventional management strategies for salicylate toxicity may be employed. Initial treatment should focus on gastrointestinal decontamination to minimize further absorption of the drug.

It is crucial to address any fluid and electrolyte imbalances that may arise due to the overdose. This can be achieved through the administration of appropriate intravenous therapy, ensuring that renal function remains adequate throughout the management process.

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. 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 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 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.

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, 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. These doses resulted in gastrointestinal and renal toxicity.

At lower oral doses of 40 mg/kg/day, minimal to slight tubular injury was noted, while doses of 160 mg/kg/day or higher in rats led to significant renal lesions, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, in dogs, oral doses of 60 mg/kg/day or higher resulted in renal lesions such as tubular atrophy, interstitial cell infiltration, chronic nephritis, and papillary necrosis.

Postmarketing Experience

No postmarketing experience details are available in the provided text.

Patient Counseling

Healthcare providers should advise patients to swallow mesalamine extended-release capsules whole, emphasizing that they should not cut, break, crush, or chew the capsules to ensure proper medication delivery. 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 to maintain hydration. Additionally, healthcare providers can inform patients that mesalamine extended-release capsules can be taken without regard to meals, providing flexibility in their dosing schedule.

Patients may notice that their urine becomes discolored reddish-brown while taking mesalamine extended-release capsules, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. Healthcare providers should instruct patients to observe their urine flow and to report any discoloration only if it is observed upon leaving the body, prior to contact with any surface or water, such as in the toilet. This distinction is crucial for appropriate monitoring and management of potential side effects.

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

View full prescribing information (PDF)