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 is chemically designated as 5-amino-2-hydroxybenzoic acid, with a molecular formula of C₇H₇NO₃ and a molecular weight of 153.14. 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 along with hydrophilic and lipophilic excipients, facilitating the extended release of the active ingredient.

Inactive ingredients in the mesalamine delayed-release tablets, USP, include colloidal silicon dioxide, ferric oxide, hypromellose, magnesium stearate, methacrylic acid and methyl methacrylate copolymer, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, talc, titanium dioxide, triethyl citrate, and an imprinting ink containing ammonium hydroxide, black iron oxide, propylene glycol, and shellac. It is important to note that FDA-approved dissolution test specifications may differ from those established by the USP.

Uses and Indications

Mesalamine delayed-release tablet is indicated for the induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis. Additionally, it is 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 this medication.

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:

  • 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 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 mesalamine therapy and monitored periodically throughout treatment. 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 therapy, mesalamine must be discontinued.

Healthcare professionals should be vigilant for symptoms of mesalamine-induced acute intolerance syndrome, which may mimic 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. Mesalamine should be discontinued if any signs of hypersensitivity are observed. Additionally, the use of mesalamine in patients with known liver impairment requires careful consideration of the associated risks and benefits.

Severe cutaneous adverse reactions warrant prompt discontinuation of mesalamine at the first indication of such reactions or any other signs of hypersensitivity, with further evaluation recommended. Caution is advised in patients with upper gastrointestinal tract obstructions, such as pyloric stenosis, as mesalamine should be avoided in these cases.

Patients should be informed about the risk of photosensitivity. Those with pre-existing skin conditions are advised to minimize 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 through standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is critical.

Healthcare professionals should also be aware that mesalamine may interfere with laboratory tests, particularly leading to spuriously elevated results when measuring urinary normetanephrine using 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 into common and serious reactions.

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, the most frequently reported adverse reactions (≥5%) include abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection.

Serious adverse reactions associated with mesalamine use 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, including myocarditis and pericarditis, require immediate evaluation and discontinuation of mesalamine if suspected. Hepatic failure is another serious risk; the benefits and risks of mesalamine should be carefully weighed in patients with known liver impairment. Severe cutaneous adverse reactions may occur, and treatment should be stopped at the first signs or symptoms of such reactions or 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 has also been reported; patients with pre-existing skin conditions are advised to take precautions against sun exposure. Nephrolithiasis has been noted in some cases, 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.

Patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any of the ingredients in mesalamine, should not use this medication. Symptoms of salicylate toxicity, which may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (such as headache, dizziness, confusion, and seizures), should be monitored closely. Severe intoxication can lead to electrolyte and blood pH imbalances, as well as potential 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

Nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), may increase the risk of nephrotoxicity when used concomitantly. It is recommended to monitor renal function and observe for any mesalamine-related adverse reactions in patients receiving these medications.

The use of azathioprine or 6-mercaptopurine in conjunction with this drug may elevate the risk of blood dyscrasias. Regular monitoring of complete blood cell counts and platelet counts is advised to detect any potential hematological complications.

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.

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 common occurrence of decreased hepatic, renal, or cardiac function, as well as the potential for concomitant diseases or other drug therapies that may affect treatment outcomes.

For induction therapy, it is advisable to initiate treatment at the lower end of the dosing range for elderly patients to mitigate the risk of adverse effects and ensure safety.

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 during pregnancy. 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.

In animal reproduction studies, oral administration of mesalamine during organogenesis in 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. Specifically, studies conducted with mesalamine during organogenesis have shown no evidence of harm to the fetus at doses up to 1000 mg/kg/day in rats and 800 mg/kg/day in rabbits.

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.

There is no clear evidence indicating that mesalamine exposure during early pregnancy is associated with an increased risk of major congenital malformations, including cardiac malformations. Given the potential risks associated with uncontrolled ulcerative colitis, healthcare providers should carefully consider the benefits and risks of mesalamine therapy in pregnant patients.

Lactation

Data from published literature indicate that mesalamine and its metabolite, N-acetyl-5-aminosalicylic acid, are present in human milk in small amounts. The relative infant doses (RID) for mesalamine are reported to be 0.1% or less. The average concentration of mesalamine in breast milk ranges from non-detectable to 0.5 mg/L, while the average concentration of N-acetyl-5-aminosalicylic acid ranges from 0.2 to 9.3 mg/L. Estimated daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day for mesalamine (RID 0% to 0.1%) and 0.03 to 1.4 mg/kg/day for N-acetyl-5-aminosalicylic acid.

There have been case reports of diarrhea in breastfed infants exposed to mesalamine. However, there is no information available regarding the effects of mesalamine on milk production. The lack of clinical data during lactation prevents a clear determination of the risk of mesalamine to an infant during this period. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for mesalamine and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Healthcare providers are advised to instruct caregivers to monitor breastfed infants for signs of diarrhea.

Renal Impairment

Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically during therapy. It is important to evaluate the risks and benefits of mesalamine in patients 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 restricted, and dosage adjustments may be necessary based on the severity of the impairment. Clinicians should exercise caution and consider alternative therapies if the risks outweigh the benefits for patients with compromised liver function.

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 the renal and hepatic systems. 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 treatment strategies for salicylate toxicity may be beneficial in managing acute overdosage. Initial management should focus on gastrointestinal decontamination to prevent further absorption of the drug. This may involve the use of activated charcoal, provided that the patient presents within an appropriate time frame post-ingestion.

Additionally, it is essential to correct any fluid and electrolyte imbalances that may arise. This can be achieved through the administration of appropriate intravenous fluids, which will also help maintain adequate renal function during the treatment process.

Given that mesalamine is a pH-dependent, delayed-release formulation, this characteristic should be taken into account when treating a suspected overdose. Monitoring and supportive care are critical components of the management strategy, ensuring that the patient is stabilized and any complications are promptly addressed.

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. Similarly, in a 104-week dietary carcinogenicity study in Wistar rats, mesalamine administered at doses up to 800 mg/kg/day did not demonstrate tumorigenic potential, representing 1.4 times the recommended human dose based on a body surface area comparison. Furthermore, no evidence of mutagenicity was detected 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. 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 renal lesions, including 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 that have been documented through voluntary reporting and surveillance programs. These events encompass a range of symptoms and conditions, some of which are rare and have been reported infrequently.

Healthcare professionals and patients are encouraged to report any adverse events or side effects that occur 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 is derived from voluntary reports and may not represent the 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 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.

Finally, remind patients to keep the medication out of reach of children and to store it as directed, to prevent accidental ingestion or misuse.

Storage and Handling

The product is supplied in a high-density polyethylene (HDPE) bottle containing 120 delayed-release tablets, equipped with a child-resistant closure. 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 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 NorthStar RxLLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)