Mesalamine

Description

Each mesalamine delayed-release tablet for oral administration contains 1.2 g of 5-aminosalicylic acid (5-ASA; mesalamine), an anti-inflammatory agent. Mesalamine is also known by its chemical name, 5-amino-2-hydroxybenzoic acid, with a molecular formula of C7H7NO3 and a molecular weight of 153.14 g/mol. Mesalamine, USP appears as light tan to pink colored, needle-shaped crystals, which may darken upon exposure to air. The substance is generally odorless, although it may possess a slight characteristic odor.

The tablet is coated with a pH-dependent polymer film that disintegrates at or above pH 6.8. The core of the tablet contains mesalamine along with hydrophilic excipients, facilitating the extended release of mesalamine. 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

Prior to initiating mesalamine therapy, healthcare professionals should evaluate the patient's renal function and continue to monitor it periodically throughout the treatment. Mesalamine delayed-release tablets must be swallowed whole; they should not be split or crushed. It is recommended that these tablets be administered with food, and patients should be encouraged to drink an adequate amount of fluids.

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

In pediatric patients weighing at least 24 kg who are capable of swallowing tablets whole, the recommended dosages for the treatment of mildly to moderately active ulcerative colitis are as follows:

• For patients weighing 24 kg to 35 kg:

  • Weeks 0 to 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:

  • Weeks 0 to 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:

  • Weeks 0 to 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, 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

Assessment of renal function is essential at the initiation of mesalamine therapy and should be conducted periodically throughout treatment. Healthcare professionals must carefully evaluate the risks and benefits of mesalamine in patients with known renal impairment or those receiving nephrotoxic medications. Should renal function deteriorate during therapy, mesalamine must be discontinued.

Healthcare providers should be vigilant for symptoms indicative of mesalamine-induced acute intolerance syndrome, which may mimic an exacerbation of ulcerative colitis. Continuous monitoring for worsening symptoms is crucial, and treatment should be halted if acute intolerance syndrome is suspected.

In cases where a hypersensitivity reaction is suspected, including but not limited to myocarditis and pericarditis, immediate evaluation of the patient is warranted, and mesalamine should be discontinued. The risks and benefits of mesalamine use must also be assessed in patients with known liver impairment.

At the first signs or symptoms of severe cutaneous adverse reactions or other indications of hypersensitivity, mesalamine should be discontinued, and further evaluation should be considered. The use of mesalamine is contraindicated in patients with pyloric stenosis or any other organic or functional obstruction.

Patients with pre-existing skin conditions should be advised to minimize sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors to mitigate the risk of skin reactions. Additionally, there have been reports of nephrolithiasis associated with mesalamine use; it is important to note that mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is imperative.

It is important to recognize that the use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection.

In summary, healthcare professionals should remain alert to the potential for hypersensitivity reactions and discontinue mesalamine immediately if such reactions are suspected. Treatment should also be stopped if acute intolerance syndrome is suspected or if severe cutaneous adverse reactions occur, with appropriate evaluation following these events. Regular assessment of renal function is critical to ensure patient safety during mesalamine therapy.

Side Effects

Patients receiving mesalamine may experience a range of adverse reactions, which can be categorized into common and serious reactions.

Common adverse reactions observed in adults (≥2%) include headache, flatulence, abnormal liver function tests, abdominal pain, and diarrhea. In pediatric patients (≥5%), the most frequently reported adverse reactions are abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection.

Serious adverse reactions necessitate careful monitoring and management. Renal impairment is a significant concern; renal function should be assessed at the beginning of treatment and periodically thereafter. Mesalamine should be discontinued if renal function deteriorates during therapy. Additionally, 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. Hepatic failure is another serious risk; the benefits and risks of mesalamine use should be carefully evaluated in patients with known liver impairment. Severe cutaneous adverse reactions warrant discontinuation of the medication at the first signs or symptoms, along with further evaluation.

Patients with pyloric stenosis or other organic or functional obstructions should avoid mesalamine due to the risk of upper gastrointestinal tract obstruction. Photosensitivity has also been reported; patients with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors. Cases of nephrolithiasis have been documented, and it is important to ensure adequate hydration during treatment, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT).

Interference with laboratory tests is another consideration; the use of mesalamine may lead to spuriously elevated results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection.

In cases of overdosage, symptoms of salicylate toxicity may manifest as nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe intoxication can result in electrolyte and blood pH imbalances, potentially leading to end-organ damage, including renal and liver impairment.

Reports from uncontrolled clinical studies and postmarketing surveillance indicate a higher incidence of blood dyscrasias, such as agranulocytosis, neutropenia, and pancytopenia, in patients aged 65 years or older taking mesalamine-containing products compared to younger patients. Therefore, it is recommended to monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine.

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 necessary 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 of mesalamine in pediatric patients was found to be similar to that observed 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

Elderly patients may exhibit different responses to mesalamine compared to younger patients, although clinical trials did not include a sufficient number of individuals aged 65 years and older to establish definitive differences in efficacy. Reports from uncontrolled clinical studies and postmarketing surveillance indicate a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in patients aged 65 and older who are treated with mesalamine-containing products.

Due to increased systemic exposures observed in elderly subjects, it is essential to monitor complete blood cell counts and platelet counts during treatment with mesalamine. Additionally, when prescribing mesalamine to geriatric patients, healthcare providers should consider the higher likelihood 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 initiate treatment at the lower end of the dosing range in elderly patients to mitigate potential risks associated with increased sensitivity to the medication.

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 all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. 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.

Increased disease activity in women with ulcerative colitis has been linked to a higher risk of adverse pregnancy outcomes, including preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g), and small for gestational age infants at birth. Despite this, there is no clear evidence that mesalamine exposure during early pregnancy is associated with an increased risk of major congenital malformations, including cardiac malformations.

Animal reproduction studies have shown no adverse developmental outcomes with the administration of oral mesalamine during organogenesis in pregnant rats and rabbits at doses 1.8 and 2.9 times, respectively, the maximum recommended human dose. Specifically, reproduction studies conducted in rats at doses up to 1000 mg/kg/day and in rabbits at doses up to 800 mg/kg/day have revealed no evidence of harm to the fetus due to mesalamine.

It is important to consider that published epidemiologic studies have significant methodological limitations that may affect the interpretation of the data, including the inability to control for confounding factors such as underlying maternal disease, concomitant medication use, and incomplete information regarding the dose and duration of mesalamine use. Therefore, healthcare professionals should weigh the potential benefits of mesalamine treatment against the risks associated with untreated ulcerative colitis during pregnancy.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers or any lactation considerations. Healthcare professionals should exercise caution and consider the potential risks and benefits when prescribing this medication to lactating mothers. Further research may be necessary to fully understand the implications for breastfed infants.

Renal Impairment

Renal function should be assessed at the beginning of treatment and periodically throughout the course of therapy in patients with renal impairment. It is essential to evaluate the risks and benefits of mesalamine in these patients, particularly those who are also taking nephrotoxic drugs. If renal function deteriorates while on mesalamine therapy, the medication should be discontinued.

Additionally, cases of nephrolithiasis have been reported in patients using mesalamine, and it is important to note that mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). To mitigate potential risks, ensuring adequate hydration during treatment is recommended.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using mesalamine. Due to the potential for altered pharmacokinetics in this population, it is essential to consider the degree of liver function compromise when determining the appropriateness of treatment. Monitoring of liver function tests may be warranted to assess the impact of mesalamine on hepatic status and to ensure patient safety. Adjustments to dosage or treatment regimens may be necessary based on the severity of hepatic impairment and the patient's overall clinical condition.

Overdosage

In cases of mesalamine overdose, 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. Therefore, prompt recognition and management of overdose symptoms are critical.

While there is no specific antidote for mesalamine overdose, conventional therapies used for salicylate toxicity may provide beneficial effects in acute cases. It is essential to consider the pH-dependent, delayed-release nature of mesalamine when evaluating and treating a suspected overdose.

Gastrointestinal tract decontamination may be necessary to prevent further absorption of the drug. This can be achieved through appropriate medical interventions. Additionally, it is crucial to correct any fluid and electrolyte imbalances by administering suitable intravenous therapy, ensuring the maintenance of adequate renal function throughout the management of the overdose.

Nonclinical Toxicology

In nonclinical studies, the teratogenic effects of mesalamine have not been evaluated, and no information is available regarding such effects. However, non-teratogenic effects were assessed, revealing no impact on fertility or reproductive performance in male or female rats at oral doses of mesalamine up to 400 mg/kg/day, which corresponds to 0.7 times the maximum recommended human dose based on a body surface area comparison.

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 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 showed that mesalamine at doses up to 800 mg/kg/day was not tumorigenic, representing 1.4 times the recommended human dose based on a body surface area comparison for mesalamine delayed-release tablets. Additionally, no evidence of mutagenicity was observed in either an in vitro Ames test or an in vivo mouse micronucleus test.

Animal studies have identified the kidney as the primary target organ for mesalamine toxicity. In a 13-week oral toxicity study in mice, as well as 13-week and 52-week oral toxicity studies in rats and cynomolgus monkeys, significant renal lesions were noted. In mice, oral daily doses of 2400 mg/kg resulted in renal lesions such as granular and hyaline casts, tubular degeneration, tubular dilation, renal infarct, papillary necrosis, tubular necrosis, and interstitial nephritis. In cynomolgus monkeys, oral 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 no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Patients should be informed that mesalamine may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic medications. 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 must 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 essential to contact their healthcare provider if they notice any signs or symptoms indicative of worsening liver function. Additionally, patients should be made aware of 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 are advised to reach out to 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 important to instruct patients to maintain adequate fluid intake 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 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 are encouraged to complete all blood tests as directed by their healthcare provider.

Patients should be instructed to swallow mesalamine delayed-release tablets whole, without splitting or crushing them, and to take the tablets with food. They should also be informed that urine may become 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.

Lastly, patients should be advised to drink an adequate amount of fluids and to contact their healthcare provider if intact, partially intact, 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 controlled room temperature of 20°C to 25°C (68°F to 77°F), in accordance with USP 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 Northstar Rx LLC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)