Mesalamine

Description

Each Mesalamine delayed-release capsule for oral administration contains four 100 mg tablets of mesalamine, USP, an aminosalicylate. Mesalamine, USP, also known as 5-aminosalicylic acid or 5-ASA, has the chemical name 5-amino-2-hydroxybenzoic acid and a structural formula of C7H7NO3. The molecular weight of mesalamine is 153.14. Each capsule includes the following inactive ingredients: colloidal silicon dioxide, dibutyl sebacate, hypromellose, iron oxide black, iron oxide red, lactose monohydrate, magnesium stearate, methacrylic acid copolymer, polyethylene glycol, potassium hydroxide, povidone, propylene glycol, shellac, sodium starch glycolate (potato), strong ammonia solution, and talc.

Uses and Indications

This drug is indicated for the treatment of mildly to moderately active ulcerative colitis in patients aged 5 years and older. Additionally, it is indicated for the maintenance of remission of ulcerative colitis in adults.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

Healthcare professionals should adhere to the following guidelines for the administration of mesalamine delayed-release capsules.

Prior to initiating treatment, it is essential to evaluate the patient's renal function. Mesalamine delayed-release capsules may be taken with or without food. Capsules must be swallowed whole; they should not be cut, broken, crushed, or chewed. For patients who have difficulty swallowing capsules, the capsules may be opened, and the inner tablets can be swallowed. It is also important to ensure that patients drink an adequate amount of fluids during treatment.

For the treatment of mildly to moderately active ulcerative colitis, the recommended dosage for adults is 800 mg, which corresponds to two 400 mg capsules, taken three times daily for a duration of 6 weeks. For pediatric patients aged 5 years or older, dosing should be determined based on the weight-based dosing table provided in the full prescribing information, with administration occurring twice daily for 6 weeks.

To maintain remission of ulcerative colitis, adults should take a total daily dose of 1.6 grams, equivalent to four 400 mg capsules, divided into two to four doses.

Contraindications

Use of mesalamine delayed-release capsules is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any of the components 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 delayed-release capsules and monitored periodically throughout the treatment course. In patients with known renal impairment or those taking nephrotoxic medications, careful evaluation of the risks and benefits of mesalamine therapy is essential. If renal function deteriorates, mesalamine delayed-release capsules should be discontinued.

Healthcare professionals should be vigilant for symptoms of mesalamine-induced Acute Intolerance Syndrome, which may mimic an exacerbation of ulcerative colitis. Patients should be monitored for any worsening of symptoms during treatment, and if acute intolerance syndrome is suspected, the treatment must be discontinued.

Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, mesalamine delayed-release capsules should be discontinued without delay.

In patients with known liver impairment, the risks and benefits of mesalamine therapy should be carefully considered. Additionally, severe cutaneous adverse reactions may occur; therefore, treatment should be stopped at the first signs or symptoms of such reactions or any other indications of hypersensitivity, and further evaluation should be undertaken.

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.

Nephrolithiasis is a potential risk associated with mesalamine therapy, as mesalamine-containing stones may not be detectable by standard radiography or computed tomography (CT). It is crucial to ensure adequate fluid intake during treatment to mitigate this risk.

Healthcare providers should also consider the iron content of mesalamine delayed-release capsules in patients who are receiving iron supplementation or are at risk of iron overload.

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 renal impairment or those on nephrotoxic drugs. In the event of a suspected hypersensitivity reaction, immediate evaluation and discontinuation of mesalamine delayed-release capsules are warranted. Treatment should also be stopped if acute intolerance syndrome is suspected or at the first signs of severe cutaneous adverse reactions or other hypersensitivity symptoms, with further evaluation considered.

Side Effects

Patients receiving mesalamine delayed-release capsules may experience a range of adverse reactions. Common adverse reactions occurring in adults (≥5%) include eructation, abdominal pain, constipation, dizziness, rhinitis, back pain, and rash. In pediatric patients, common adverse reactions (≥5%) consist of nasopharyngitis, headache, abdominal pain, dizziness, sinusitis, rash, cough, and diarrhea.

Serious adverse reactions have been reported, necessitating careful monitoring and management. Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically thereafter. The risks and benefits of using mesalamine in these patients, particularly those taking nephrotoxic drugs, should be evaluated, and renal function should be monitored closely. Mesalamine delayed-release capsules should be discontinued if renal function deteriorates.

Mesalamine-induced Acute Intolerance Syndrome may occur, with symptoms that can be difficult to distinguish from an exacerbation of ulcerative colitis. Patients should be monitored for worsening symptoms during treatment, and mesalamine should be discontinued if acute intolerance syndrome is suspected. Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation and discontinuation of the medication if such reactions are suspected.

Hepatic failure is another serious concern; the risks and benefits of mesalamine should be carefully considered in patients with known liver impairment. Severe cutaneous adverse reactions may also occur, and treatment should be discontinued at the first signs or symptoms of such reactions or other signs of hypersensitivity.

Patients should be advised about the risk of photosensitivity and are encouraged to avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors. Additionally, nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate fluid intake during treatment is essential to mitigate this risk.

It is important to consider the iron content of mesalamine delayed-release capsules in patients who are taking iron supplements or are at risk of iron overload. 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.

In cases of overdosage, symptoms of salicylate toxicity may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication can result in electrolyte and blood pH imbalances and may lead to involvement of other organs, including renal and hepatic systems.

Drug Interactions

There are currently no documented drug interactions associated with the use of this medication. Additionally, there is no information available regarding 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 delayed-release capsules for the treatment of mildly to moderately active ulcerative colitis in pediatric patients aged 5 to 17 years have been established through adequate and well-controlled studies utilizing mesalamine delayed-release 400 mg tablets. Evidence supporting the use of mesalamine delayed-release capsules in this age group is derived from both adult studies and a specific 6-week study involving 82 pediatric patients within the same age range.

However, the safety and effectiveness of mesalamine delayed-release capsules for treating mildly to moderately active ulcerative colitis in pediatric patients under the age of 5 years have not been established. Additionally, the safety and effectiveness of mesalamine delayed-release capsules for the maintenance of remission of ulcerative colitis in pediatric patients remain unproven.

Geriatric Use

Clinical studies of mesalamine delayed-release tablets did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently than younger patients. However, reports from uncontrolled clinical studies and postmarketing experience indicate a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine delayed-release tablets compared to younger patients taking mesalamine-containing products, such as mesalamine delayed-release capsules.

It is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine delayed-release capsules. Additionally, when prescribing mesalamine delayed-release capsules to geriatric 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. These factors may necessitate dose adjustments and careful monitoring to ensure patient safety and therapeutic efficacy.

Pregnancy

There are no adequate and well-controlled studies of mesalamine use in pregnant women. Limited published human data indicate that mesalamine does not increase the overall rate of congenital malformations. However, some studies suggest an increased rate of preterm birth, stillbirth, and low birth weight; it remains unclear whether these adverse pregnancy outcomes are attributable to mesalamine, underlying maternal disease, or both, as active inflammatory bowel disease is also associated with such outcomes.

All pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations and 15% to 20% for pregnancy loss. In prospective and retrospective studies involving over 600 women exposed to mesalamine during pregnancy, the observed rate of congenital malformations did not exceed the background rate in the general population. Animal reproduction studies conducted in rats and rabbits at oral doses up to 480 mg/kg/day during organogenesis revealed no evidence of fetal harm or impaired fertility, with doses approximately 1.9 times (rat) and 3.9 times (rabbit) the recommended human dose showing no adverse effects.

Mesalamine crosses the placenta, and its use during pregnancy should be considered only if clearly needed. Given the potential risks associated with both the medication and the underlying condition, healthcare professionals should carefully evaluate the benefits and risks of mesalamine therapy in pregnant patients.

Lactation

Mesalamine and its N-acetyl metabolite are present in human milk. In published lactation studies, maternal mesalamine doses from various oral and rectal formulations ranged from 500 mg to 3 g daily. The concentration of mesalamine in milk ranged from non-detectable to 0.11 mg/L, while the concentration of the N-acetyl-5-aminosalicylic acid metabolite ranged from 5 mg/L to 18.1 mg/L.

Based on these concentrations, estimated infant daily doses for an exclusively breastfed infant are as follows:

• Mesalamine: 0 mg/kg/day to 0.017 mg/kg/day

• N-acetyl-5-aminosalicylic acid: 0.75 mg/kg/day to 2.72 mg/kg/day.

The developmental and health benefits of breastfeeding should be considered alongside the mother’s clinical need for mesalamine and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. Caution should be exercised when mesalamine delayed-release capsules are administered to a nursing woman.

Renal Impairment

Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically during treatment. It is important to evaluate the risks and benefits of using mesalamine delayed-release capsules in these patients, particularly those with known renal impairment or those taking nephrotoxic drugs. Continuous monitoring of renal function is essential. If there is any deterioration in renal function, mesalamine delayed-release capsules should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using mesalamine delayed-release capsules. Due to the potential for altered pharmacokinetics in this population, it is essential to consider the degree of liver function compromise when prescribing this medication. Monitoring of liver function tests may be warranted to ensure patient safety and to assess the need for any dosage adjustments. The prescribing physician should remain vigilant for any signs of hepatic dysfunction during treatment and adjust the therapeutic approach accordingly.

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. The presence of these symptoms necessitates immediate medical evaluation and intervention.

Severe salicylate intoxication can result in significant complications, including electrolyte and blood pH imbalances, which may lead to renal and liver involvement. Therefore, it is crucial to monitor the patient's vital signs and laboratory parameters closely.

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 should be considered to prevent further absorption of the drug. This may involve the administration of activated charcoal, provided that the patient is alert and able to protect their airway.

Management of fluid and electrolyte imbalances is essential in overdose situations. Appropriate intravenous therapy should be initiated to correct these imbalances and to maintain adequate renal function. It is important to note that mesalamine delayed-release capsules are pH dependent, which should be taken into account when treating a suspected overdose, as this may influence the drug's absorption and elimination.

In summary, prompt recognition of symptoms, appropriate decontamination, and supportive care are critical components in the management of mesalamine overdosage.

Nonclinical Toxicology

Mesalamine was evaluated for its carcinogenic potential in both rats and mice. In these studies, mesalamine did not demonstrate carcinogenicity at dietary doses of up to 480 mg/kg/day in rats and 2000 mg/kg/day in mice. These doses correspond to approximately 2.9 and 6.1 times the maximum recommended maintenance dose of mesalamine, which is 1.6 grams per day or 26.7 mg/kg/day based on a 60 kg body weight.

In terms of mutagenic potential, mesalamine was found to be negative in the Ames assay for mutagenesis. Additionally, it did not induce sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells in vitro, nor did it induce micronuclei in mouse bone marrow polychromatic erythrocytes.

Regarding reproductive toxicity, mesalamine was administered at oral doses up to 480 mg/kg/day, which is approximately 1.9 times the recommended human treatment dose on a body surface area basis. The results indicated no adverse effects on fertility or reproductive performance in both male and female rats.

Animal studies revealed that the kidney was the primary organ affected by mesalamine toxicity. In rats, single doses ranging from approximately 750 mg/kg to 1000 mg/kg, which are about 3 to 4 times the recommended human dose based on body surface area, resulted in renal papillary necrosis. Chronic administration of doses of 170 and 360 mg/kg/day, approximately 0.7 and 1.5 times the recommended human dose based on body surface area, led to significant renal damage, including papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.

In mice, administration of oral doses of 4000 mg/kg/day of mesalamine, approximately 8 times the recommended human dose based on body surface area, for three months resulted in tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis.

In canine studies, single doses of 6000 mg of delayed-release mesalamine tablets, which is about 8 times the recommended human dose based on body surface area, caused renal papillary necrosis, although these doses were not fatal. Chronic administration of mesalamine at doses of 80 mg/kg/day, approximately 1.1 times the recommended human dose based on body surface area, also resulted in renal changes in dogs.

Postmarketing Experience

Postmarketing experience has identified cases of mesalamine-induced acute intolerance syndrome, which may present with symptoms including cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, and rash. Additionally, severe cutaneous adverse reactions have been reported. Instances of hypersensitivity reactions have also been noted, leading to recommendations for patients to discontinue use and report any symptoms to their healthcare provider.

Reports of renal function impairment have been associated with mesalamine therapy, particularly in patients with pre-existing renal impairment or those concurrently using nephrotoxic drugs. Furthermore, discoloration of urine to reddish-brown has been observed in patients taking mesalamine, especially when urine comes into contact with hypochlorite-containing bleach.

Patient Counseling

Patients should be informed that if they are transitioning from a previous oral mesalamine therapy to mesalamine delayed-release capsules, they must discontinue their prior oral mesalamine therapy and adhere to the dosing instructions for the delayed-release capsules. It is important to clarify that two mesalamine delayed-release 400 mg capsules cannot be substituted for one mesalamine delayed-release 800 mg tablet.

Patients may take mesalamine delayed-release capsules with or without food. They should be instructed to swallow the capsules whole and not to cut, break, crush, or chew them. For those who have difficulty swallowing the capsules, they may carefully open the capsules and swallow the contents, which consist of four 100 mg tablets. Patients should open only the number of capsules needed to achieve a complete dose, ensuring that all tablets are swallowed without retention in the mouth. The tablets should also be swallowed whole, without cutting, breaking, crushing, or chewing. It is advisable for patients to drink an adequate amount of fluids while on this medication.

Patients should be made aware that intact, partially intact, and/or tablet shells may appear in their stool. If this occurs repeatedly, they should contact their healthcare provider. Additionally, patients may notice that their urine becomes discolored reddish-brown while taking mesalamine delayed-release capsules, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. They should be advised to observe 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.

Patients must be instructed to protect mesalamine delayed-release capsules from moisture by tightly closing the container and leaving any desiccant pouches present in the bottle along with the capsules. It is essential to inform patients that mesalamine delayed-release capsules may decrease renal function, especially 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 informed about the signs and symptoms of hypersensitivity reactions. They must be instructed to discontinue the use of mesalamine delayed-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, malaise, conjunctivitis, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, it is important to inform them of the signs and symptoms of worsening liver function and to advise them to report any such signs or symptoms to their healthcare provider. Patients should also be made aware of the signs and symptoms of severe cutaneous adverse reactions and instructed to stop taking mesalamine delayed-release capsules and report to their healthcare provider at the first appearance of such reactions or any other signs 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. They should maintain adequate fluid intake during treatment to minimize the risk of kidney stone formation and 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.

Patients should inform their healthcare provider if they are taking iron-containing supplements. Elderly patients and those taking azathioprine or 6-mercaptopurine should be made aware of the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. They should be advised to complete all blood tests ordered by their healthcare provider.

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 20º to 25ºC (68º to 77ºF), in compliance 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)