Mesalamine

Description

Each mesalamine delayed-release tablet for oral administration contains 1.2 g of mesalamine, also known as 5-aminosalicylic acid, with the chemical name 5-amino-2-hydroxybenzoic acid. The molecular formula is C7H7NO3, and it has a molecular weight of 153.14 g/mol. Mesalamine, USP appears as light tan to pink colored, needle-shaped crystals that may darken upon exposure to air and is generally odorless or may have a slight characteristic odor. The tablet is coated with a pH-dependent polymer film that disintegrates at or above pH 6.8. Inactive ingredients in each tablet include carboxymethylcellulose sodium, colloidal silicon dioxide, hypromellose, iron oxide red, iron oxide yellow, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, triethyl citrate, talc, and titanium dioxide.

Uses and Indications

Mesalamine delayed-release tablets are indicated for the induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis. Additionally, these tablets are indicated for the treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg.

There are no teratogenic or nonteratogenic effects associated with the use of mesalamine delayed-release tablets.

Dosage and Administration

Healthcare professionals should evaluate renal function prior to the initiation of mesalamine therapy and periodically during treatment. Mesalamine delayed-release tablets must be swallowed whole; they should not be split or crushed. It is recommended to administer mesalamine delayed-release tablets with food and ensure that patients drink an adequate amount of fluids.

For adults, the recommended dosage for the induction of remission is 2.4 g to 4.8 g (equivalent to two to four 1.2 g tablets) taken once daily. For the maintenance of remission, the dosage is 2.4 g (two 1.2 g tablets) once daily.

In pediatric patients weighing at least 24 kg who can swallow tablets whole, the recommended dosage for the treatment of mildly to moderately active ulcerative colitis is as follows:

• For patients weighing 24 kg to 35 kg:

  • Week 0 to Week 8: 2.4 g (two 1.2 g tablets) once daily.

  • After Week 8: 1.2 g (one 1.2 g tablet) once daily.

• For patients weighing greater than 35 kg to 50 kg:

  • Week 0 to Week 8: 3.6 g (three 1.2 g tablets) once daily.

  • After Week 8: 2.4 g (two 1.2 g tablets) once daily.

• For patients weighing greater than 50 kg:

  • Week 0 to Week 8: 4.8 g (four 1.2 g tablets) once daily.

  • After Week 8: 2.4 g (two 1.2 g tablets) once daily.

Contraindications

Use of mesalamine delayed-release tablets is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, as well as 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 and monitored periodically throughout the course of therapy. It is essential to evaluate the risks and benefits of mesalamine in patients with known renal impairment or those taking nephrotoxic medications. Should renal function deteriorate during treatment, mesalamine must be discontinued.

Healthcare professionals should be vigilant for symptoms indicative of mesalamine-induced acute intolerance syndrome, which may be challenging to differentiate from an exacerbation of ulcerative colitis. Monitoring for any worsening of symptoms is crucial, and treatment should be halted if acute intolerance syndrome is suspected.

Hypersensitivity reactions, including myocarditis and pericarditis, necessitate immediate evaluation. If a hypersensitivity reaction is suspected, mesalamine should be discontinued without delay.

In patients with known liver impairment, a careful assessment of the risks and benefits of mesalamine is required due to the potential for hepatic failure.

Severe cutaneous adverse reactions may occur; therefore, treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation may be warranted in these cases.

Mesalamine is contraindicated in patients with upper gastrointestinal tract obstruction, including pyloric stenosis or any other organic or functional obstruction.

Patients with pre-existing skin conditions should be advised about the risk of photosensitivity. It is recommended that they avoid excessive sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors.

There have been reports of nephrolithiasis associated with mesalamine use. Notably, mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). To mitigate this risk, it is important to ensure adequate hydration during treatment.

Finally, healthcare professionals should be aware that the use of mesalamine may interfere with laboratory tests, specifically leading to spuriously elevated results when measuring urinary normetanephrine using liquid chromatography with electrochemical detection.

Side Effects

Patients receiving mesalamine may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Most common adverse reactions observed in clinical trials include headache, flatulence, liver function test abnormalities, abdominal pain, and diarrhea in adults, occurring in 2% or more of participants. In pediatric patients, the most frequently reported adverse reactions (≥5%) include abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection.

Serious adverse reactions necessitating careful monitoring include renal impairment, where renal function should be assessed at the beginning of treatment and periodically thereafter. The risks and benefits of mesalamine should be evaluated in patients with known renal impairment or those taking nephrotoxic drugs. Mesalamine should be discontinued if renal function deteriorates during therapy.

Mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. 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 mesalamine if suspected.

Patients with known liver impairment should be evaluated for the risks and benefits of mesalamine use, as hepatic failure has been reported. Severe cutaneous adverse reactions warrant discontinuation of the medication at the first signs or symptoms, along with further evaluation for hypersensitivity.

Upper gastrointestinal tract obstruction is a concern, particularly in patients with pyloric stenosis or other organic or functional obstructions, and mesalamine should be avoided in these cases. Additionally, patients should be advised about the risk of photosensitivity, particularly those with pre-existing skin conditions, and should take precautions against sun exposure.

Nephrolithiasis has been reported in patients using mesalamine, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to mitigate this risk.

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.

Patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any of the ingredients in mesalamine delayed-release tablets, should not use this medication.

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 intoxication can lead to electrolyte and blood pH imbalances, potentially resulting in end-organ damage, including renal and liver impairment.

Drug Interactions

There are currently no documented drug interactions associated with 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 have been established for the treatment of mildly to moderately active ulcerative colitis in pediatric patients weighing at least 24 kg. Evidence supporting its use in this population includes data from adequate and well-controlled trials in adults, as well as a multicenter, randomized, double-blind, parallel group trial involving 105 pediatric patients aged 5 to 17 years.

The safety profile observed in pediatric patients was similar to that reported in adults. However, the safety and effectiveness of mesalamine delayed-release tablets have not been established in patients weighing less than 24 kg.

Geriatric Use

Clinical trials of mesalamine did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently from younger patients. However, reports from uncontrolled clinical studies and postmarketing surveillance have indicated a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients taking mesalamine-containing products compared to their younger counterparts.

Elderly patients may experience increased systemic exposures to mesalamine. Therefore, it is essential to monitor complete blood cell counts and platelet counts in this population during treatment. Additionally, when prescribing mesalamine to geriatric patients, healthcare providers should consider the greater frequency of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

For induction therapy, it is advisable to consider starting at the low end of the dosing range for elderly patients to mitigate potential risks associated with higher doses.

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. However, it is important to note that adverse effects on maternal and fetal outcomes are associated with ulcerative colitis in pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown, although in the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is approximately 2% to 4% and 15% to 20%, respectively.

In animal reproduction studies, administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.8 and 2.9 times the maximum recommended human dose, respectively, did not result in adverse developmental outcomes. Furthermore, there is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk of major congenital malformations, including cardiac malformations.

It is also noted that increased disease activity in women with ulcerative colitis is associated with a higher risk of adverse pregnancy outcomes, which may include preterm delivery, low birth weight infants, and small for gestational age at birth. However, published epidemiologic studies have important methodological limitations that hinder the interpretation of the data, including the inability to control for confounders such as underlying maternal disease, concomitant medication use, and incomplete information regarding the dose and duration of mesalamine use.

Healthcare professionals should consider these factors when counseling pregnant patients or women of childbearing potential regarding the use of mesalamine.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers. Additionally, there is no data on the potential for excretion in breast milk or its effects on breastfed infants. Healthcare professionals should consider these factors when advising lactating mothers.

Renal Impairment

Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically during therapy. It is essential to evaluate the risks and benefits of mesalamine in individuals with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates while on therapy, mesalamine should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using mesalamine. Due to the potential for altered drug metabolism and excretion in this population, close monitoring of liver function is recommended. It is essential to assess liver enzymes and other relevant parameters prior to initiating treatment and periodically during therapy.

In cases of significant liver dysfunction, the use of mesalamine may be contraindicated, and alternative therapies should be considered. Adjustments to the dosage regimen may be necessary based on the severity of hepatic impairment, and clinicians should remain vigilant for any signs of liver-related adverse effects throughout the course of treatment.

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 intoxication with salicylates can result in significant electrolyte and blood pH imbalances, which may lead to end organ damage, particularly affecting renal and liver function. It is crucial to recognize these potential complications early in the management of an overdose.

Currently, there is no specific antidote for mesalamine overdose. However, conventional therapies used for salicylate toxicity may provide beneficial effects in acute cases. Healthcare providers should consider gastrointestinal tract decontamination to prevent further absorption of the drug, especially if the overdose is identified shortly after ingestion.

Management of mesalamine overdosage should also focus on correcting fluid and electrolyte imbalances. This can be achieved through the administration of appropriate intravenous therapy, ensuring that renal function is adequately maintained throughout the treatment process.

It is important to note that mesalamine is 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

In a 104-week dietary carcinogenicity study conducted in CD-1 mice, mesalamine administered at doses up to 2500 mg/kg/day did not demonstrate tumorigenic potential. This dose is approximately 2.2 times the maximum recommended human dose based on a body surface area comparison for mesalamine delayed-release tablets. Similarly, a 104-week dietary carcinogenicity study in Wistar rats revealed that mesalamine at doses up to 800 mg/kg/day was also non-tumorigenic, corresponding to 1.4 times the recommended human dose based on body surface area.

No evidence of mutagenicity was identified in either an in vitro Ames test or an in vivo mouse micronucleus test, indicating that mesalamine does not pose a mutagenic risk.

Regarding reproductive toxicity, no adverse effects on fertility or reproductive performance were observed in male or female rats administered oral doses of mesalamine up to 400 mg/kg/day, which is 0.7 times the maximum recommended human dose based on body surface area.

In terms of animal toxicology, studies have indicated that the kidney is the primary target organ for mesalamine toxicity. A 13-week oral toxicity study in mice, along with 13-week and 52-week oral toxicity studies in rats and cynomolgus monkeys, revealed significant renal lesions. In mice, daily oral doses of 2400 mg/kg resulted in granular and hyaline casts, tubular degeneration, tubular dilation, renal infarct, papillary necrosis, tubular necrosis, and interstitial nephritis. In cynomolgus monkeys, daily doses of 250 mg/kg or higher led to nephrosis, papillary edema, and interstitial fibrosis.

Postmarketing Experience

No specific postmarketing experience details have been reported. As such, there are currently no additional adverse events or rare case reports available for review.

Patient Counseling

Patients should be informed that mesalamine may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic drugs. Periodic monitoring of renal function will be conducted during therapy, and patients are advised to complete all blood tests ordered by their healthcare provider.

Patients should be instructed to discontinue mesalamine 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, as well as any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, it is important to contact their healthcare provider if they notice any signs or symptoms indicative of worsening liver function. Additionally, patients should be informed about the signs and symptoms of severe cutaneous adverse reactions. They should stop taking mesalamine delayed-release tablets and report to their healthcare provider at the first appearance of any severe cutaneous adverse reaction or other signs of hypersensitivity.

Patients should also be advised to contact their healthcare provider if they experience signs and symptoms of upper gastrointestinal tract obstruction. Those with pre-existing skin conditions should be counseled to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

It is essential for patients to drink an adequate amount of fluids during treatment to minimize the risk of kidney stone formation. They should 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.

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. Patients are encouraged to complete all blood tests as directed by their healthcare provider.

Patients should be instructed to swallow mesalamine delayed-release tablets whole and not to split or crush them. It is also recommended that they take mesalamine delayed-release tablets with food.

Patients may notice that their urine becomes discolored reddish-brown while taking mesalamine delayed-release tablets when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. If discolored urine is observed, patients 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 (e.g., in the toilet).

Lastly, patients should be instructed to drink an adequate amount of fluids and to contact their healthcare provider if intact, partially intact, and/or tablet shells are repeatedly observed in the stool.

Storage and Handling

The product is supplied in a tight, light-resistant container to ensure its integrity and efficacy. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality of the product throughout its shelf life.

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

View full prescribing information (PDF)