Mesalamine

Uses and Indications

Mesalamine extended-release capsules are indicated for the induction of remission and for the treatment of mildly to moderately active ulcerative colitis in adult patients.

Limitations of Use: There are no teratogenic or nonteratogenic effects associated with the use of mesalamine extended-release capsules as per the available data.

Dosage and Administration

The recommended dosage for the medication is 1 g, administered orally four times daily. Healthcare professionals should instruct patients to swallow the capsules whole, ensuring they are not crushed or chewed to maintain the integrity of the formulation.

As an alternative, the capsule(s) may be opened, and the contents can be sprinkled onto a small amount of applesauce or yogurt for easier ingestion. It is essential for patients to consume an adequate amount of fluids while taking this medication to facilitate proper absorption and minimize gastrointestinal discomfort.

Contraindications

Use of mesalamine extended-release capsules 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 (5.1, 7.1, 8.6).

In cases where mesalamine-induced acute intolerance syndrome is suspected, characterized by symptoms such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash, treatment should be discontinued immediately (5.2).

Healthcare professionals should remain vigilant for hypersensitivity reactions, which may include myocarditis and pericarditis. If any signs of hypersensitivity are observed, mesalamine should be discontinued (5.3).

For patients with known liver impairment, a careful assessment of the risks and benefits of mesalamine use is warranted, as hepatic failure may occur (5.4).

Severe cutaneous adverse reactions have been reported; therefore, mesalamine should be discontinued at the first indication of such reactions or any other signs of hypersensitivity, with consideration for further evaluation (5.5).

Patients should be advised to avoid sun exposure if they have pre-existing skin conditions, as photosensitivity may occur (5.6). Additionally, 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). Adequate hydration should be maintained during treatment to mitigate this risk (5.7).

Mesalamine may interfere with laboratory tests, specifically leading to elevated urinary normetanephrine test results (5.8).

Side Effects

In clinical trials, the most common adverse reactions observed in patients receiving mesalamine (≥1%) included diarrhea (3%), headache (2%), nausea (2%), abdominal pain (2%), dyspepsia (2%), vomiting (2%), and rash (1%). Other adverse reactions reported in less than 1% of patients encompassed a range of systems and conditions.

Serious adverse reactions have been noted, particularly in the cardiac, hematologic, hepatic, immune, nervous, renal, respiratory, and skin systems. Cardiac disorders included chest pain, fatal myocarditis, pericarditis, and T-wave abnormalities. Hematologic disorders reported were agranulocytosis, anemia, aplastic anemia, leukopenia, and pancytopenia. Hepatic disorders included cirrhosis, jaundice (including cholestatic jaundice), hepatotoxicity, hepatitis, and possible hepatocellular damage, with some cases resulting in liver necrosis and failure, which were occasionally fatal. Immune system disorders reported included anaphylactic reactions, angioedema, lupus-like syndrome, and systemic lupus erythematosus.

Nervous system disorders included intracranial hypertension, while renal and urinary disorders encompassed acute renal failure, chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, and nephrotic syndrome. Respiratory disorders included hypersensitivity pneumonitis (which may involve interstitial pneumonitis, allergic alveolitis, and eosinophilic pneumonitis), interstitial lung disease, pleurisy/pleuritis, and pneumonitis. Skin and subcutaneous tissue disorders reported included AGEP, DRESS, and SJS/TEN.

Additional adverse reactions of note include mesalamine-induced acute intolerance syndrome, characterized by symptoms such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. Hypersensitivity reactions, including myocarditis and pericarditis, have also been documented. Cases of nephrolithiasis have been reported, with mesalamine-containing stones being undetectable by standard radiography or CT. Furthermore, urine discoloration may occur ex vivo due to contact with hypochlorite-containing bleach.

In summary, while many patients tolerate mesalamine well, healthcare providers should remain vigilant for both common and serious adverse reactions, particularly in patients with pre-existing conditions or those receiving concurrent therapies.

Drug Interactions

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

When azathioprine or 6-mercaptopurine is administered alongside this drug, 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 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

Safety and effectiveness in pediatric patients have not been established. Therefore, the use of this medication in children, infants, and adolescents should be approached with caution, as there is insufficient data to support its use in these populations. Healthcare professionals are advised to consider alternative treatments or therapies that have been validated for pediatric use.

Geriatric Use

Clinical trials of mesalamine did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently from younger patients. However, reports from uncontrolled clinical studies and postmarketing surveillance have indicated a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine-containing products compared to younger adults. This increased risk may be associated with factors such as ulcerative colitis, the use of interacting drugs, or reduced renal function.

It is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine. Additionally, when prescribing mesalamine to patients aged 65 years and older, healthcare providers should consider the greater frequency of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies that may affect treatment outcomes.

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. It is important to note that adverse effects on maternal and fetal outcomes are associated with ulcerative colitis itself during pregnancy. The background risk of major birth defects and miscarriage in the general population is estimated to be 2% to 4% and 15% to 20%, respectively, although the specific background risk for the indicated populations remains unknown.

Animal reproduction studies have shown that oral administration of mesalamine during organogenesis in pregnant rats at doses up to 1000 mg/kg/day (approximately 2.4 times the maximum recommended human dose of 4 g/day, based on body surface area comparison) and in rabbits at doses of 800 mg/kg/day (approximately 3.9 times the maximum recommended human dose) revealed no evidence of adverse developmental effects.

Increased disease activity in women with ulcerative colitis has been associated with a higher risk of adverse pregnancy outcomes, including preterm delivery, low birth weight infants, and small for gestational age at birth. While published data suggest that mesalamine exposure during early pregnancy (first trimester) and throughout pregnancy does not correlate with an increased risk of major congenital malformations, including cardiac malformations, the methodological limitations of these studies, such as the inability to control for confounding factors, must be considered when interpreting the data.

Healthcare professionals should remain vigilant regarding the management of ulcerative colitis in pregnant patients, as the disease itself poses risks that may impact pregnancy outcomes.

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 limits the ability to clearly determine 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, whether from mesalamine or from the underlying maternal condition.

Caregivers should be advised to monitor breastfed infants for signs of diarrhea.

Renal Impairment

Patients with renal impairment, including conditions such as minimal change disease, acute and chronic interstitial nephritis, and renal failure, have been reported in those receiving mesalamine or products containing mesalamine. It is essential to evaluate the risks and benefits of using mesalamine in patients with known renal impairment, a history of renal disease, or those taking concomitant nephrotoxic drugs.

Renal function should be assessed in all patients prior to the initiation of mesalamine therapy and monitored periodically throughout treatment. If renal function deteriorates during therapy, mesalamine should be discontinued. Regular evaluation of renal function is crucial to ensure patient safety and effective management.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of hepatic failure when administered mesalamine, particularly those with pre-existing liver disease. It is essential for healthcare providers to carefully evaluate the risks and benefits of using mesalamine in this population. Close monitoring of liver function is recommended for patients with compromised liver function to ensure safety and efficacy.

Overdosage

In cases of mesalamine overdosage, symptoms consistent with salicylate toxicity may manifest. These symptoms can include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and various neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe intoxication may result in significant electrolyte and blood pH imbalances, potentially leading to damage of vital organs, including the kidneys and liver.

There is currently no specific antidote available for mesalamine overdose. However, conventional treatment strategies for salicylate toxicity may be employed to manage acute overdosage. These strategies typically involve gastrointestinal tract decontamination to minimize further absorption of the drug.

Management of mesalamine overdosage should also focus on correcting any fluid and electrolyte imbalances. This can be achieved through the administration of appropriate intravenous therapy, which is essential for maintaining adequate renal function during the treatment process. Healthcare professionals are advised to monitor the patient closely for any signs of complications and to provide supportive care as needed.

Nonclinical Toxicology

In a 104-week dietary carcinogenicity study, mesalamine was administered to CD-1 mice at doses up to 2500 mg/kg/day, with no evidence of tumorigenicity observed. This dose corresponds to approximately 2.5 times the maximum recommended human dose based on body surface area. Similarly, in a 104-week dietary carcinogenicity study conducted in Wistar rats, mesalamine was given at doses up to 800 mg/kg/day, which also did not result in tumor formation. This dose is approximately 1.5 times the maximum recommended human dose on a body surface area basis.

Regarding mutagenicity, no evidence was found in both an in vitro Ames test and an in vivo mouse micronucleus test. Additionally, no effects on fertility or reproductive performance were noted in male or female rats at oral doses of mesalamine up to 400 mg/kg/day, which is 0.8 times the maximum recommended human dose based on body surface area. There is no information available concerning teratogenic effects.

Postmarketing Experience

During post-approval use of mesalamine, various adverse reactions have been reported voluntarily from a population of uncertain size. As a result, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders include chest pain, fatal myocarditis, pericarditis, and T-wave abnormalities.

Hematologic Disorders reported include agranulocytosis, anemia, aplastic anemia, leukopenia, and pancytopenia.

Hepatic Disorders encompass cirrhosis, jaundice (including cholestatic jaundice), hepatotoxicity, hepatitis, and possible hepatocellular damage, which may include liver necrosis and liver failure; some cases were fatal. Additionally, one case of Kawasaki-like syndrome with hepatic function changes was noted.

Immune System Disorders include anaphylactic reactions, angioedema, lupus-like syndrome, and systemic lupus erythematosus.

Nervous System Disorders have been reported as intracranial hypertension.

Renal and Urinary Disorders consist of acute renal failure, chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, and nephrotic syndrome. Urine discoloration occurring ex vivo has been observed due to contact of mesalamine, including its inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Reproductive System and Breast Disorders include reversible oligospermia.

Respiratory, Thoracic and Mediastinal Disorders reported are hypersensitivity pneumonitis (which includes interstitial pneumonitis, allergic alveolitis, and eosinophilic pneumonitis), interstitial lung disease, pleurisy/pleuritis, and pneumonitis.

Skin and Subcutaneous Tissue Disorders include AGEP, DRESS, and SJS/TEN.

Patient Counseling

Patients should be informed that mesalamine extended-release capsules may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic medications. It is essential for patients to understand that periodic monitoring of renal function will be conducted during their therapy, and they should complete all blood tests as ordered by their healthcare provider.

Patients must be instructed to discontinue mesalamine extended-release capsules and promptly report to their healthcare provider if they experience new or worsening symptoms indicative of acute intolerance syndrome, such as cramping, abdominal pain, bloody diarrhea, fever, headache, or rash. Additionally, patients with a history of liver disease should be advised to contact their healthcare provider if they notice any signs or symptoms of worsening liver function.

It is important to inform patients about the signs and symptoms of severe cutaneous adverse reactions. They should be instructed to stop taking mesalamine extended-release capsules and report to their healthcare provider at the first appearance of any severe cutaneous adverse reaction or other signs of hypersensitivity.

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

Patients should be instructed to maintain adequate fluid intake during treatment to reduce the risk of kidney stone formation. They should also be advised to 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. It is crucial for these patients to complete all blood tests as ordered by their healthcare provider.

Patients must be instructed to swallow mesalamine extended-release capsules whole and not to crush or chew them. Alternatively, they may open the capsules and sprinkle the contents onto applesauce or yogurt for easier consumption.

Patients should be made aware that their urine may become discolored reddish-brown while taking mesalamine extended-release capsules, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. They should observe their urine flow and report to their healthcare provider only if the urine is discolored upon leaving the body, before contact with any surface or water, such as in the toilet.

Finally, patients should be reminded to drink an adequate amount of fluids throughout their treatment.

Storage and Handling

The product is supplied in tight, light-resistant containers to ensure its integrity. 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 quality and efficacy of the product.

Additional Clinical Information

Postmarketing experience has revealed several adverse events associated with mesalamine. Cardiac disorders may include chest pain, fatal myocarditis, pericarditis, and T-wave abnormalities. Hematologic disorders reported include agranulocytosis, anemia, aplastic anemia, leukopenia, and pancytopenia. Hepatic disorders such as cirrhosis, jaundice (including cholestatic jaundice), hepatotoxicity, and hepatitis have been noted, with some cases resulting in fatal outcomes. Additionally, there have been reports of immune system disorders like anaphylactic reactions and lupus-like syndromes, as well as nervous system disorders including intracranial hypertension. Renal and urinary disorders encompass acute and chronic renal failure, interstitial nephritis, and nephrolithiasis. Other notable conditions include reversible oligospermia in the reproductive system, hypersensitivity pneumonitis in the respiratory system, and severe skin reactions such as AGEP, DRESS, and SJS/TEN.

Clinicians should counsel patients regarding potential renal impairment, particularly in those with pre-existing conditions or those taking nephrotoxic medications, emphasizing the importance of regular monitoring of renal function. Patients should be instructed to discontinue mesalamine and report any symptoms indicative of mesalamine-induced acute intolerance syndrome or hypersensitivity reactions. Those with liver disease should be vigilant for signs of hepatic failure. Patients should also be informed about the risk of severe cutaneous adverse reactions and the need for sun protection due to photosensitivity. Adequate hydration is essential to minimize the risk of nephrolithiasis, and patients should be aware of the potential for urine discoloration due to contact with hypochlorite-containing surfaces. Finally, elderly patients and those on specific immunosuppressive therapies should be monitored for blood disorders, with adherence to blood testing protocols emphasized.

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)