Mesalamine

Description

Each mesalamine extended-release capsule, USP contains 0.375 g of mesalamine USP (5-aminosalicylic acid, 5-ASA), an aminosalicylate. The molecular formula of mesalamine is C7H7NO3, and its molecular weight is 153.14. The capsules contain granules composed of mesalamine in a polymer matrix with an enteric coating that dissolves at pH 6 and above. The inactive ingredients include microcrystalline cellulose, ethyl cellulose, hypromellose, methacrylic acid and methyl methacrylate copolymer (1:1), triethyl citrate, talc, gelatin, FD&C Blue 2, titanium dioxide, shellac, potassium hydroxide, and black iron oxide.

Uses and Indications

Mesalamine extended-release capsules are 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 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, a careful evaluation of the risks and benefits is essential. If there is any deterioration in renal function, discontinuation of the 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. Close monitoring for worsening symptoms is advised, and treatment should be discontinued if acute intolerance syndrome is suspected.

Hypersensitivity reactions, including but not limited to myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, the treatment must be discontinued promptly.

In patients with pre-existing 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 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 applying a broad-spectrum sunscreen when outdoors.

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 fluid intake during treatment to mitigate this risk.

General precautions include the potential for interference with laboratory tests. Specifically, the use of mesalamine may lead to spuriously elevated results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection.

Regular monitoring of renal function is recommended throughout the treatment period to ensure patient safety and treatment efficacy.

Side Effects

Most common adverse reactions observed in clinical trials, occurring in 3% or more of patients, include headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis.

Serious adverse reactions may occur, necessitating careful monitoring and evaluation. Patients with known renal impairment or those taking nephrotoxic drugs should have their renal function assessed at the beginning of treatment and periodically thereafter. It is crucial to evaluate the risks and benefits of treatment in these patients, and discontinuation is advised if renal function deteriorates.

Mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Therefore, patients should be monitored for worsening symptoms, 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 such a reaction is suspected. Additionally, severe cutaneous adverse reactions warrant discontinuation at the first signs or symptoms, along with consideration for further evaluation.

Patients with known liver impairment should be carefully evaluated for the risks and benefits of treatment due to the potential for hepatic failure.

Nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Patients are advised to ensure adequate fluid intake during treatment to mitigate this risk.

Photosensitivity is another concern; patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

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.

Additional adverse reactions may occur in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or any component of mesalamine extended-release capsules. Symptoms of salicylate toxicity can include 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

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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 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. There is no clear evidence suggesting that mesalamine exposure during early pregnancy is linked to an increased risk of major congenital malformations, including cardiac malformations. However, it is important to recognize that published epidemiologic studies have significant methodological limitations that complicate data interpretation, including the inability to control for confounding factors such as underlying maternal disease and concomitant medication use, as well as incomplete information regarding the dose and duration of mesalamine use.

Reproductive studies involving mesalamine during organogenesis have been conducted in rats at oral doses up to 320 mg/kg/day (approximately 1.7 times the recommended human dose based on body surface area comparison) and in rabbits at doses up to 495 mg/kg/day (approximately 5.4 times the recommended human dose based on body surface area comparison), with no evidence of fetal harm observed.

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 known renal impairment or those taking nephrotoxic drugs, it is essential to evaluate the risks and benefits of treatment while closely monitoring 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 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, headache, dizziness, confusion, and seizures.

Severe intoxication with salicylates can result in significant complications, including electrolyte and blood pH imbalances, which may lead to renal and liver damage. Therefore, prompt recognition and management of these symptoms are critical.

There is currently no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may provide some benefit. In cases of acute overdosage, gastrointestinal tract decontamination may be necessary to prevent further absorption of the drug.

Management should also focus on correcting fluid and electrolyte imbalances through appropriate intravenous therapy, ensuring adequate renal function is maintained throughout the treatment process. It is important to note that mesalamine extended-release capsules are a pH-dependent delayed-release formulation, which should be taken into account when treating a suspected overdose.

Nonclinical Toxicology

Dietary mesalamine was not found to be carcinogenic in rats at doses as high as 480 mg/kg/day, nor in mice at 2,000 mg/kg/day. 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 (30 mg/kg based on a 50 kg body weight or 1,110 mg/m²), respectively, when adjusted for body surface area.

In mutagenicity studies, mesalamine demonstrated negative results in 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. Furthermore, no adverse effects on fertility or reproductive performance were observed in male and female rats administered oral mesalamine doses 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 observed in mice and rats, with single oral doses of 800 mg/kg (about 2.2 times the recommended human dose based on body surface area) and 1,800 mg/kg (about 9.7 times the recommended human dose based on body surface area) resulting in gastrointestinal and renal toxicity.

In rats, oral doses of 40 mg/kg/day (approximately 0.20 times the human dose based on body surface area) led to minimal to slight tubular injury, while doses of 160 mg/kg/day (about 0.90 times the human dose based on body surface area) or higher resulted in 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 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 revealed reports of several adverse reactions associated with the use of the medication. These include acute intolerance syndrome, hypersensitivity reactions, severe cutaneous adverse reactions, and nephrolithiasis.

Cases of mesalamine-induced acute intolerance syndrome have been documented, characterized by symptoms such as cramping, abdominal pain, bloody diarrhea, fever, headache, and rash. Severe cutaneous adverse reactions have also been reported, which necessitate immediate discontinuation of mesalamine and prompt reporting to a healthcare provider.

Additionally, nephrolithiasis, or kidney stones, has been noted in postmarketing reports. Patients are advised to maintain adequate fluid intake to minimize the risk of developing kidney stones and to report any signs or symptoms indicative of this condition, such as severe side or back pain or blood in the urine.

Patient Counseling

Healthcare providers should advise patients to swallow mesalamine extended-release capsules whole and to avoid cutting, breaking, crushing, or chewing the capsules. It is important to inform patients to refrain from co-administering these capsules with antacids and to ensure they drink an adequate amount of fluids during treatment.

Patients may take mesalamine extended-release capsules without regard to meals. They should be made aware that their urine may become discolored reddish-brown when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. If patients observe discolored urine, they should 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.

Healthcare providers should inform patients that mesalamine extended-release capsules may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic drugs, including NSAIDs. Periodic monitoring of renal function will be conducted during therapy, and patients should be advised to complete all blood tests ordered by their healthcare provider.

Patients should be educated on the signs and symptoms of hypersensitivity reactions. They must be instructed to discontinue the use of mesalamine extended-release capsules and report to their healthcare provider if they experience new or worsening symptoms of Acute Intolerance Syndrome, which may include cramping, abdominal pain, bloody diarrhea, fever, headache, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, healthcare providers should inform them of the signs and symptoms of worsening liver function and advise them to report any such signs or symptoms to their healthcare provider. Additionally, patients should be made aware of the signs and symptoms of severe cutaneous adverse reactions. They should be instructed to stop taking mesalamine extended-release capsules and report to their healthcare provider at the first appearance of a severe cutaneous adverse reaction or any other sign of hypersensitivity.

Patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. Furthermore, healthcare providers should instruct patients to drink an adequate amount of fluids during treatment to minimize the risk of kidney stone formation and to contact their healthcare provider if they experience signs or symptoms of a kidney stone, such as severe side or back pain or blood in the urine.

Finally, elderly patients and those taking azathioprine or 6-mercaptopurine should be informed of the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. Patients should be encouraged to complete all blood tests ordered by their healthcare provider.

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

View full prescribing information (PDF)