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 chemically designated as 5-amino-2-hydroxybenzoic acid, with a molecular formula of C₇H₇NO₃ and a molecular weight of 153.14. The substance appears as light tan to pink colored, needle-shaped crystals, which may darken upon exposure to air and are generally odorless or possess a slight characteristic odor.

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 comprises mesalamine combined with hydrophilic excipients, facilitating the extended release of the active ingredient. Each mesalamine delayed-release tablet, USP, also contains the following inactive ingredients: 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. The product complies with USP Dissolution Test 4.

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 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 the 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 dosages for the treatment of mildly to moderately active ulcerative colitis are 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, 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

Healthcare professionals should be aware of several critical warnings and precautions associated with the use of mesalamine to ensure patient safety and effective treatment outcomes.

Renal Function Monitoring It is essential to assess renal function at the initiation of mesalamine therapy and to conduct periodic evaluations throughout the treatment course. The risks and benefits of mesalamine should be carefully considered in patients with known renal impairment or those receiving nephrotoxic medications. Should renal function deteriorate during treatment, mesalamine must be discontinued.

Acute Intolerance Syndrome Symptoms indicative of mesalamine-induced acute intolerance syndrome may closely resemble an exacerbation of ulcerative colitis. Therefore, healthcare providers should monitor patients for any worsening of symptoms while on mesalamine. If acute intolerance syndrome is suspected, treatment should be discontinued immediately.

Hypersensitivity Reactions Immediate evaluation is warranted if a hypersensitivity reaction is suspected, which may include serious conditions such as myocarditis and pericarditis. Mesalamine should be discontinued without delay in such cases.

Liver Impairment Considerations The use of mesalamine in patients with known liver impairment requires careful risk-benefit assessment.

Severe Cutaneous Adverse Reactions At the first signs or symptoms of severe cutaneous adverse reactions or any other indications of hypersensitivity, mesalamine should be discontinued, and further evaluation should be considered.

Obstruction Precautions Mesalamine is contraindicated in patients with pyloric stenosis or any other organic or functional obstruction.

Sun Exposure Precautions Patients with pre-existing skin conditions should be advised to minimize sun exposure, wear protective clothing, and utilize a broad-spectrum sunscreen when outdoors to mitigate the risk of skin reactions.

Nephrolithiasis Risk Reports of nephrolithiasis associated with mesalamine use have been documented. Notably, mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). Therefore, it is crucial to ensure adequate hydration during treatment to reduce the risk of stone formation.

Laboratory Test Considerations Healthcare professionals should be aware that the use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection.

In summary, careful monitoring of renal function, vigilance for hypersensitivity reactions, and appropriate patient education regarding sun exposure and hydration are vital components of safe mesalamine therapy.

Side Effects

Most common adverse reactions observed in clinical trials include headache, flatulence, liver function test abnormalities, abdominal pain, and diarrhea in adults, with an incidence of 2% or greater. In pediatric patients, adverse reactions occurring at a frequency of 5% or greater include abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection.

Serious adverse reactions necessitate 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. 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; thus, monitoring for worsening symptoms is essential, and treatment should be discontinued if this syndrome is suspected.

Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation and discontinuation of mesalamine if such reactions are suspected. The use of mesalamine in patients with known liver impairment should be approached with caution, weighing the risks and benefits. 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 been reported; therefore, patients with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and use broad-spectrum sunscreen when outdoors.

Nephrolithiasis has been reported in association with mesalamine use, and it is important to note that mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is recommended to mitigate this risk.

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. 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. 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 result in electrolyte and blood pH imbalances, potentially leading to end-organ damage, including renal and liver impairment.

Drug Interactions

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

Additionally, the use of azathioprine or 6-mercaptopurine in conjunction with this medication may elevate the risk of blood dyscrasias. Regular monitoring of complete blood cell counts and platelet counts is recommended 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 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, 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, 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 when prescribing mesalamine to geriatric patients.

For elderly patients, it is advisable to initiate treatment at the lower end of the dosing range for induction 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 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 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 in 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, 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 lactating mothers or its effects on breastfed infants. The prescribing information does not address the potential for excretion in breast milk or any associated risks for infants related to breastfeeding. The focus of the insert is primarily on pregnancy and its associated risks, without providing guidance or considerations for breastfeeding.

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 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 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 cases of salicylate intoxication can result in significant electrolyte and blood pH imbalances, potentially leading to end-organ damage, particularly affecting the renal and hepatic systems.

Management of mesalamine overdosage does not have a specific antidote; however, conventional treatment strategies for salicylate toxicity may be employed. Initial management should focus on gastrointestinal decontamination to minimize 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 due to the overdose. Administration of appropriate intravenous fluids is recommended to restore balance and support renal function. Given that mesalamine is a pH-dependent, delayed-release formulation, this characteristic should be taken into account when devising a treatment plan for suspected overdose cases. Continuous monitoring of the patient's clinical status and laboratory parameters is essential to guide further management and ensure patient safety.

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 corresponds to 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, representing 1.4 times the recommended human dose based on body surface area comparison.

No evidence of mutagenicity was identified in either an in vitro Ames test or an in vivo mouse micronucleus test. Additionally, assessments of fertility and reproductive performance in male and female rats indicated no adverse effects at 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 comparison.

In terms of animal pharmacology and toxicology, studies involving mesalamine have identified the kidney as 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 that oral daily doses of 2400 mg/kg in mice and 1150 mg/kg in rats resulted in significant renal lesions. These lesions included 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

The postmarketing experience for the drug associated with SPL code 90375-7 includes reports of additional adverse events received through voluntary reporting and surveillance programs. These events encompass a range of symptoms and conditions, some of which are rare and have been documented in isolated case reports.

Healthcare professionals and patients are encouraged to report any adverse events or side effects encountered during the use of this medication. The information gathered from these reports contributes to the ongoing assessment of the drug's safety profile.

It is important to note that the reported events do not imply a causal relationship with the medication, as the data reflects voluntary reports and may not represent the overall incidence of these events in the general population.

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 during treatment.

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

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 adjust treatment as necessary. This ongoing communication is vital for ensuring the safety and effectiveness of the therapy.

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

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

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 Zydus Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)