Mesalamine

Description

Each mesalamine extended-release capsule USP 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 mesalamine is formulated in granules within a polymer matrix that features an enteric coating, which dissolves at a pH of 6 and above.

Inactive ingredients in the mesalamine extended-release capsules include colloidal silicon dioxide, hypromellose, magnesium stearate, methacrylic acid copolymer Type A (comprising poly (methacrylic acid-co-methyl methacrylate) and sodium lauryl sulfate), microcrystalline cellulose, polyacrylate dispersion 40 percent (containing nonoxynol 100 and poly (ethyl acrylate-co-methyl methacrylate)), simethicone emulsion, talc, titanium dioxide, and triethyl citrate. The empty hard gelatin capsule shell is composed of D&C Red 22, FD&C Blue 1, gelatin, sodium lauryl sulfate, and titanium dioxide. The capsules are imprinted with black ink, which contains black iron oxide, potassium hydroxide, and shellac. It is noted that FDA-approved dissolution test specifications may differ from those established by the USP.

Uses and Indications

Mesalamine extended-release capsules are indicated for the maintenance of remission of ulcerative colitis in adults. There are no reported 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. Co-administration with antacids should be avoided to ensure optimal efficacy. 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.

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

Healthcare professionals are advised to conduct a thorough assessment of renal function at the initiation of treatment with mesalamine and to monitor renal function periodically throughout the treatment course. Special attention should be given to patients with known renal impairment or those concurrently using nephrotoxic medications; in such cases, a careful evaluation of the risks and benefits is essential. Should there be any deterioration in renal function, discontinuation of mesalamine is warranted.

It is important to monitor patients for symptoms indicative of Mesalamine-Induced Acute Intolerance Syndrome, as these symptoms may closely resemble an exacerbation of ulcerative colitis. If acute intolerance syndrome is suspected, treatment should be discontinued immediately.

Healthcare providers must remain vigilant for signs of hypersensitivity reactions, including myocarditis and pericarditis. In the event of such reactions, immediate evaluation is necessary, and mesalamine should be discontinued.

For patients with pre-existing liver impairment, a careful assessment of the risks and benefits of continuing treatment with mesalamine is recommended. Additionally, at the first indication of severe cutaneous adverse reactions or other hypersensitivity signs, treatment should be halted, and further evaluation should be considered.

Patients with existing skin conditions should be counseled to minimize sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors to mitigate the risk of skin reactions.

It is noteworthy that mesalamine-containing stones are not detectable through standard radiographic techniques or computed tomography (CT). Therefore, ensuring adequate fluid intake during treatment is crucial to prevent stone formation.

Healthcare professionals should also be aware that the use of mesalamine may result in spuriously elevated test results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection.

In summary, healthcare providers should maintain a high index of suspicion for hypersensitivity reactions and acute intolerance syndrome, and they should act promptly to discontinue treatment and evaluate the patient as necessary. Regular monitoring of renal function is essential to ensure patient safety throughout the treatment process.

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 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 acute intolerance 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 are also advised to be cautious of photosensitivity; those with pre-existing skin conditions should avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors. Nephrolithiasis has been noted, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate fluid intake during treatment is recommended 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, aminosalicylates, or any component of mesalamine extended-release capsules should be closely monitored. Symptoms of salicylate toxicity, which include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (such as headache, dizziness, confusion, and seizures), should be recognized. Severe salicylate intoxication may result in electrolyte and blood pH imbalances, potentially leading to damage to other organs, including renal and hepatic systems.

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.

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.

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 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.

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 2500 g), and small for gestational age infants at birth.

Furthermore, 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 and weigh the potential benefits against the risks, particularly in the context of the patient's disease activity and overall health.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers. Additionally, there are no data on the excretion of this medication in breast milk or its potential 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. If there is any deterioration in renal function, discontinuation of the treatment is recommended.

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 dysfunction when determining the appropriateness of therapy. Monitoring of liver function is recommended to ensure patient safety and to adjust treatment as necessary. Healthcare providers should remain vigilant in assessing any potential adverse effects related to compromised liver function throughout 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 through the administration of appropriate intravenous therapy. Maintaining adequate renal function is also a critical component of the management strategy.

Given that mesalamine extended-release capsules are a pH-dependent delayed-release formulation, this characteristic should be taken into account when treating a suspected overdose. Monitoring and supportive care should be tailored to the individual patient's needs, with close observation for any evolving symptoms or complications.

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 (equivalent to 30 mg/kg for a 50 kg individual or 1,110 mg/m²), 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 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 (approximately 2.2 times the recommended human dose based on body surface area) for mice and 1,800 mg/kg (approximately 9.7 times the recommended human dose based on body surface area) for rats, both of which resulted in gastrointestinal and renal toxicity.

In rats, oral doses of 40 mg/kg/day (about 0.20 times the human dose based on body surface area) led to minimal to slight tubular injury. Higher doses of 160 mg/kg/day (approximately 0.90 times the human dose based on body surface area) or more resulted in renal lesions, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, in dogs, oral doses of 60 mg/kg/day (approximately 1.1 times the human dose based on body surface area) or higher caused 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 highlighted 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 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. Mesalamine extended-release capsules can be taken without regard to meals, providing flexibility in the patient's 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, before any contact with surfaces or water, such as in the toilet.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature. 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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)