Mesalamine

Description

Each mesalamine delayed-release tablet, USP for oral administration contains 1.2 g of 5-aminosalicylic acid (5-ASA; mesalamine), an anti-inflammatory agent. Mesalamine, USP is characterized as an almost white to light brown to light tan to pink colored powder. It exhibits slight solubility in water and very slight solubility in methanol, dehydrated alcohol, and acetone, while being practically insoluble in n-butyl alcohol, chloroform, ether, ethyl acetate, n-hexane, methylene chloride, and n-propyl alcohol. Mesalamine is soluble in 10% v/v hydrochloric acid and in 10% w/v alkali hydroxides. The chemical name for mesalamine is 5-amino-2-hydroxybenzoic acid.

The tablet is coated with a pH-dependent polymer film that disintegrates at or above pH 6.8, typically in the terminal ileum, where mesalamine is released from the tablet core. The core of the tablet contains mesalamine along with hydrophilic excipients, facilitating the extended release of mesalamine. Inactive ingredients include carboxymethyl cellulose sodium, colloidal silicon dioxide, ferric oxide red, hypromellose, magnesium stearate, methacrylic acid copolymer (type A), methacrylic acid copolymer (type B), microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc, titanium dioxide, and triethyl citrate. The imprinting ink consists of ferrosoferric oxide, propylene glycol, and shellac glaze. This formulation meets USP dissolution Test 5.

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, this medication is indicated for the treatment of mildly to moderately active ulcerative colitis in pediatric patients who weigh 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 therapy with mesalamine delayed-release tablets, 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 advised 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, the dosage is 2.4 g (two 1.2-g tablets) once daily from Week 0 to Week 8, followed by 1.2 g (one 1.2-g tablet) once daily after Week 8.

• For patients weighing greater than 35 kg to 50 kg, the dosage is 3.6 g (three 1.2-g tablets) once daily from Week 0 to Week 8, followed by 2.4 g (two 1.2-g tablets) once daily after Week 8.

• For patients weighing greater than 50 kg, the dosage is 4.8 g (four 1.2-g tablets) once daily from Week 0 to Week 8, followed by 2.4 g (two 1.2-g tablets) once daily after Week 8.

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

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 receiving nephrotoxic medications. Should renal function deteriorate during treatment, mesalamine delayed-release tablets must be discontinued.

Healthcare professionals should be vigilant for symptoms 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 discontinued 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. Additionally, the use of mesalamine in patients with known liver impairment requires careful consideration of the associated risks and benefits.

Severe cutaneous adverse reactions may occur; therefore, treatment should be halted at the first indication of such reactions or any other signs of hypersensitivity, with further evaluation recommended. Mesalamine is contraindicated in patients with upper gastrointestinal tract obstruction, including pyloric stenosis or other organic or functional obstructions.

Patients should be advised about the risk of photosensitivity. Those with pre-existing skin conditions should take precautions to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors. Furthermore, cases of nephrolithiasis have been reported in patients using mesalamine. It is important to note that mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). Adequate hydration should be maintained during treatment to mitigate this risk.

Healthcare professionals should also be aware that the use of mesalamine may interfere with laboratory tests, specifically 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 to ensure patient safety.

Side Effects

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

Most 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. Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically thereafter. The risks and benefits of mesalamine should be evaluated in these patients, particularly those taking nephrotoxic drugs. If renal function deteriorates during therapy, mesalamine delayed-release tablets should be discontinued.

Mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Therefore, it is crucial to monitor for any worsening symptoms during treatment and discontinue mesalamine if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of mesalamine if such reactions are suspected. Additionally, hepatic failure has been reported; thus, the risks and benefits of mesalamine use should be carefully considered in patients with known liver impairment.

Severe cutaneous adverse reactions have been noted, and treatment should be discontinued at the first signs or symptoms of such reactions or any other signs of hypersensitivity. Patients with pyloric stenosis or other organic or functional obstructions should avoid mesalamine due to the risk of upper gastrointestinal tract obstruction.

Photosensitivity is another concern; 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 also been reported, and it is important to ensure adequate hydration during treatment, as mesalamine-containing stones are undetectable by standard radiography or computed tomography.

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 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.

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.

Drug Interactions

The concomitant use of nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), may lead to an increased risk of nephrotoxicity. It is recommended to monitor renal function closely and observe for any mesalamine-related adverse reactions.

When azathioprine or 6-mercaptopurine is administered alongside this medication, there is an elevated risk of blood dyscrasias. Regular monitoring of complete blood cell counts and platelet counts is advised to detect any potential hematological abnormalities.

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 have not been established in patients weighing less than 24 kg, and caution is advised when considering treatment in this subgroup.

Geriatric Use

Elderly patients may exhibit different responses to mesalamine compared to younger patients, as clinical trials did not include a sufficient number of individuals aged 65 years and older to establish definitive differences in efficacy or safety. 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 these factors.

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. However, it is important to note that adverse effects on maternal and fetal outcomes are associated with ulcerative colitis itself during pregnancy.

In animal reproduction studies, administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.8 and 2.9 times, respectively, the maximum recommended human dose did not result in adverse developmental outcomes. Despite this, the estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown, as 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.

In women with ulcerative colitis, increased disease activity has been linked to 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. While published data suggest that mesalamine exposure in early pregnancy is not associated with an increased risk of major congenital malformations, including cardiac malformations, the methodological limitations of these epidemiologic studies must be acknowledged. These limitations include 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.

Given the available data, healthcare professionals should carefully consider the potential risks and benefits of mesalamine therapy in pregnant patients, particularly in the context of the underlying condition of ulcerative colitis.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers or its effects on lactation. Consequently, healthcare professionals should exercise caution when prescribing this medication to lactating mothers, as the potential risks to breastfed infants are not well characterized. It is advisable to consider the benefits of breastfeeding alongside the potential risks associated with the medication.

Renal Impairment

Renal function should be assessed at the beginning of treatment and periodically throughout therapy in patients with renal impairment. It is essential to evaluate the risks and benefits of mesalamine in these patients, particularly those taking nephrotoxic drugs. If renal function deteriorates during treatment, mesalamine delayed-release tablets should be discontinued.

Additionally, cases of nephrolithiasis have been reported in patients using mesalamine. Notably, mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is crucial to mitigate this risk.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using mesalamine. It is essential to consider the potential impact of compromised liver function on the pharmacokinetics and safety profile of the medication. Close monitoring of liver function is recommended for these patients to ensure that any adverse effects are promptly identified and managed. Adjustments to the dosage may be necessary based on the severity of liver impairment and the patient's overall clinical condition.

Overdosage

In cases of mesalamine overdosage, symptoms may reflect those associated with salicylate toxicity. Healthcare professionals should be vigilant for signs such as nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and various neurologic manifestations, including headache, dizziness, confusion, and seizures. Severe cases of salicylate intoxication can result in significant electrolyte and blood pH imbalances, potentially leading to end-organ damage, particularly affecting the kidneys and liver.

Management of mesalamine overdosage does not have a specific antidote; however, conventional treatment strategies for salicylate toxicity may be applicable. Immediate actions should include gastrointestinal decontamination to limit further absorption of the drug. This may involve the use of activated charcoal if the patient presents within an appropriate time frame post-ingestion.

It is crucial to address any fluid and electrolyte imbalances that may arise. The administration of intravenous fluids and electrolytes should be tailored to the individual patient's needs to ensure adequate renal function is maintained throughout the treatment process.

Additionally, it is important to consider that mesalamine is a pH-dependent, delayed-release formulation. This characteristic should be taken into account when evaluating and managing a suspected overdose, as it may influence the timing and effectiveness of therapeutic interventions.

Nonclinical Toxicology

In nonclinical studies, no teratogenic effects were observed. Additionally, no effects on fertility or reproductive performance were noted in male or female rats administered 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 at doses up to 2500 mg/kg/day was found to be non-tumorigenic. 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 demonstrated that mesalamine at doses up to 800 mg/kg/day was also non-tumorigenic, representing 1.4 times the recommended human dose based on a body surface area comparison for mesalamine delayed-release tablets. Furthermore, no evidence of mutagenicity was detected in either an in vitro Ames test or an in vivo mouse micronucleus test.

In terms of animal pharmacology and toxicology, studies involving mesalamine indicated that the kidney is the primary target organ for 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, 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

Postmarketing experience has identified additional adverse events reported voluntarily or through surveillance programs. These events include, but are not limited to, rare case reports of hypersensitivity reactions, including anaphylaxis, and instances of liver enzyme elevations. Reports of gastrointestinal disturbances, such as nausea and diarrhea, have also been noted. Other events include skin reactions, such as rash and urticaria. It is important to note that the frequency of these events is not established, and the relationship to the drug has not been definitively determined.

Patient Counseling

Advise patients to take the medication exactly as prescribed by their healthcare provider. It is important for patients to understand the dosage and frequency of administration to ensure optimal therapeutic outcomes.

Inform patients about the potential side effects associated with the medication. Patients should be made aware of common side effects, as well as any serious adverse reactions that may require immediate medical attention. Encourage patients to report any unusual symptoms or side effects they experience while taking the medication.

Discuss the importance of adherence to the prescribed treatment regimen. Emphasize that missing doses can affect the effectiveness of the therapy and may lead to complications.

Instruct patients to avoid certain activities or substances that may interact with the medication. This may include specific foods, alcohol, or other medications that could lead to adverse effects or reduced efficacy.

Encourage patients to maintain regular follow-up appointments to monitor their progress and any potential side effects. This will help ensure that the treatment remains effective and safe.

Remind patients to keep the medication out of reach of children and to store it according to the instructions provided, ensuring its safety and integrity.

Lastly, advise patients to consult their healthcare provider before making any changes to their medication regimen or if they have any questions or concerns regarding their treatment.

Storage and Handling

The product is supplied in a child-resistant package designed to ensure safety. It is essential to store the product at a temperature range of 20° C to 25° C (68° F to 77° F), in accordance with USP Controlled Room Temperature guidelines. Additionally, it is crucial to keep the product out of reach of children to prevent accidental ingestion or misuse.

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 Sun Pharmaceutical Industries, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)