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 of the tablet comprises mesalamine along with hydrophilic and lipophilic excipients, facilitating the extended release of mesalamine. Inactive ingredients 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 differ from those of 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

Healthcare professionals should evaluate renal function prior to the initiation of mesalamine delayed-release tablets and periodically during therapy. 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 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 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 indicative of mesalamine-induced acute intolerance syndrome, which may mimic an exacerbation of ulcerative colitis. If such symptoms arise, treatment should be discontinued immediately.

Hypersensitivity reactions, including but not limited to myocarditis and pericarditis, necessitate immediate evaluation. Mesalamine should be discontinued if a hypersensitivity reaction is suspected.

In patients with known liver impairment, careful consideration of the risks and benefits of mesalamine use is warranted due to the potential for hepatic failure.

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

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, including wearing protective clothing and using a broad-spectrum sunscreen when outdoors.

There have been reports of nephrolithiasis associated with mesalamine use. It is important to note that mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). To mitigate this risk, patients should be encouraged to maintain adequate hydration during treatment.

The use of mesalamine may interfere with laboratory tests, particularly leading to spuriously elevated results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection.

In the event of a suspected hypersensitivity reaction, immediate evaluation is required, and mesalamine should be discontinued. Additionally, treatment should be halted if acute intolerance syndrome is suspected or at the first signs of severe cutaneous adverse reactions or other hypersensitivity symptoms, with consideration for further evaluation.

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, abnormal liver function tests, 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 associated with mesalamine require 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, necessitate immediate evaluation and discontinuation of mesalamine if such reactions are 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.

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 of 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, as severe intoxication can lead to electrolyte and blood pH imbalances, and potentially result in 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 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 indicate that the use of mesalamine during pregnancy has not been reliably associated 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. Furthermore, there is no clear evidence that mesalamine exposure in early pregnancy is linked to an increased risk of major congenital malformations, including cardiac malformations.

The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown. 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, published data suggest that increased disease activity is correlated with 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 at birth.

Given these considerations, healthcare professionals should weigh the benefits of mesalamine treatment against potential risks in pregnant patients, particularly those with active ulcerative colitis.

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. Maternal doses of mesalamine from various oral and rectal formulations have ranged from 500 mg to 4.8 g daily. The average concentration of mesalamine in breast milk has been found to range from non-detectable to 0.5 mg/L, while the average concentration of N-acetyl-5-aminosalicylic acid in milk has ranged 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.

Due to the lack of clinical data during lactation, a clear determination of the risk of mesalamine to an infant cannot be made. 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 drug or from the underlying maternal condition. Caregivers should be advised to monitor breastfed infants for diarrhea.

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 individuals with known renal impairment or those who are taking nephrotoxic drugs. If there is any deterioration in renal function while on mesalamine therapy, the medication 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, close monitoring of liver function is recommended. It is essential to assess liver enzymes and other relevant laboratory values 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 the renal and hepatic systems. Therefore, prompt recognition and management of these complications are critical.

While there is no specific antidote for mesalamine overdose, conventional therapies for salicylate toxicity may be beneficial. 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.

It is essential to correct any fluid and electrolyte imbalances through the administration of appropriate intravenous therapy. Maintaining adequate renal function is also a priority during the management of an overdose.

Given that mesalamine is a pH-dependent, delayed-release formulation, this characteristic must be taken into account when treating a suspected overdose. Continuous monitoring and supportive care are crucial to ensure patient safety and recovery.

Nonclinical Toxicology

In nonclinical studies, no information regarding teratogenic effects was provided. However, non-teratogenic effects were evaluated, revealing no impact on fertility or reproductive performance 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 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 body surface area comparison. 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 body surface area comparison. 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

The postmarketing experience for the drug associated with SPL code 90375-7 includes reports of additional adverse events received voluntarily or through surveillance programs. These reports encompass a range of events, some of which are rare and may not have been observed during clinical trials.

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 events reported do not imply a causal relationship with the drug, as the data reflects voluntary reporting and may include confounding factors. Continuous monitoring and evaluation of postmarketing data are essential for ensuring patient safety and effective risk management.

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. Patients should be counseled on the potential consequences of missed doses and the appropriate steps to take if a dose is forgotten.

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 affect the efficacy or safety of the treatment.

Emphasize the need for regular follow-up appointments to monitor the patient's response to the medication and to make any necessary adjustments to the treatment plan. Encourage patients to communicate openly with their healthcare provider about their progress and any concerns they may have.

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

Storage and Handling

The product is supplied in high-density polyethylene (HDPE) bottles with child-resistant closures. Available configurations include bottles containing 120 delayed-release tablets and bottles containing 500 delayed-release tablets.

Storage conditions require the product to be maintained at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to ensure that the product is stored in a manner that protects it from moisture and extreme temperatures to maintain its integrity and efficacy.

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

View full prescribing information (PDF)