Mesalamine

Description

The active ingredient in Mesalamine suppositories, USP 1000 mg, is mesalamine, also known as mesalazine or 5-aminosalicylic acid (5-ASA). Chemically, mesalamine is identified as 5-amino-2-hydroxybenzoic acid and is classified as an aminosalicylate. Each suppository contains 1000 mg of micronized mesalamine in a base of hard fat. The mesalamine is presented as light tan to pink colored, needle-shaped crystals, which may darken upon exposure to air. The substance is generally odorless, although it may exhibit a slight characteristic odor.

In terms of solubility, mesalamine is slightly soluble in water and very slightly soluble in methanol, dehydrated alcohol, and acetone. It is practically insoluble in n-butyl alcohol, chloroform, ether, ethyl acetate, n-hexane, methylene chloride, and n-propyl alcohol, but is soluble in dilute hydrochloric acid and dilute alkali hydroxides. The molecular formula of mesalamine is C7H7NO3, with a molecular weight of 153.14.

Uses and Indications

Mesalamine is indicated for the treatment of mildly to moderately active ulcerative proctitis in adults.

Limitations of Use: The safety and efficacy of mesalamine in populations other than adults with mildly to moderately active ulcerative proctitis have not been established. There are no reported teratogenic or nonteratogenic effects associated with mesalamine in the available data.

Dosage and Administration

The recommended adult dosage of mesalamine is 1000 mg, administered rectally once daily at bedtime for a duration of 3 to 6 weeks. The safety and effectiveness of mesalamine beyond 6 weeks have not been established.

Prior to initiating therapy with mesalamine, healthcare professionals should evaluate the patient's renal function and continue to monitor it periodically throughout the treatment.

When administering the suppository, it is important to ensure that it is not cut or broken. Patients should be advised to drink an adequate amount of fluids to facilitate the treatment. After insertion, the suppository should be retained for one to three hours, or longer if possible, to maximize its therapeutic effect.

Healthcare professionals should also inform patients that mesalamine suppositories may cause staining of surfaces that come into direct contact with them, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. It is advisable to keep mesalamine suppositories away from these surfaces to prevent any potential staining.

Contraindications

Use is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any ingredients in the formulation. This is due to the potential for severe allergic reactions in these individuals.

Warnings and Precautions

Evaluate the risks and benefits of mesalamine treatment in patients with known renal impairment or those taking nephrotoxic drugs. It is essential to monitor renal function closely in these individuals. Should renal function deteriorate, 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. Continuous monitoring for worsening symptoms is crucial, and treatment should be halted if acute intolerance syndrome is suspected.

In cases where a hypersensitivity reaction is suspected, including but not limited to myocarditis and pericarditis, immediate evaluation of the patient is warranted, and mesalamine should be discontinued.

For patients with known liver impairment, a careful assessment of the risks and benefits of mesalamine therapy is necessary. Treatment should be stopped at the first signs or symptoms of severe cutaneous adverse reactions or any other indications of hypersensitivity, with further evaluation considered.

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

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 to prevent stone formation.

Healthcare providers should be aware that spurious elevations in test results may occur with liquid chromatography with electrochemical detection in patients receiving mesalamine suppositories. In such cases, it is recommended to utilize an alternative, selective assay for normetanephrine to obtain accurate results.

Regular monitoring of renal function is advised for patients with renal impairment or those on nephrotoxic medications. Additionally, when assessing normetanephrine levels in patients using mesalamine suppositories, the use of a selective assay is necessary to avoid misleading test outcomes.

Side Effects

Patients receiving mesalamine may experience a range of adverse reactions. Common adverse reactions occurring in 1% or more of patients include dizziness, rectal pain, fever, rash, acne, and colitis.

Serious adverse reactions have been reported, necessitating careful monitoring and evaluation. Renal impairment is a significant concern; it is essential to assess the risks and benefits in patients with known renal impairment or those taking nephrotoxic drugs, with renal function monitored closely. Mesalamine should be discontinued if renal function deteriorates. Additionally, mesalamine-induced acute intolerance syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Therefore, 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 consideration; the risks and benefits should be evaluated in patients with known liver impairment. Severe cutaneous adverse reactions have been reported, and treatment should be discontinued at the first signs or symptoms of such reactions or other signs of hypersensitivity, with further evaluation considered.

Patients may also experience photosensitivity; those with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. Nephrolithiasis has been noted, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is crucial to mitigate this risk.

In terms of laboratory interactions, patients receiving mesalamine suppositories may experience spuriously elevated test results for urinary normetanephrine when using liquid chromatography with electrochemical detection; alternative, selective assays for normetanephrine should be utilized.

In pediatric patients, adverse reactions such as abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting have been observed, mirroring those seen in adult patients.

Geriatric patients, particularly those aged 65 years or older, may have a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, as reported in uncontrolled clinical studies and postmarketing reporting systems. It is recommended to monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine suppositories.

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, as well as to observe for any mesalamine-related adverse reactions.

When administered alongside azathioprine or 6-mercaptopurine, there is an elevated risk of blood disorders. Regular monitoring of complete blood cell counts and platelet counts is recommended to detect any potential hematological complications early.

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 suppositories for the treatment of mildly to moderately active ulcerative proctitis in pediatric patients have not been established. In a 6-week, open-label, single-arm study involving 49 patients aged 5 to 17 years, mesalamine suppositories were evaluated; however, efficacy was not demonstrated. The study included only 14 patients with histologically confirmed ulcerative proctitis.

Adverse reactions observed in pediatric patients during this trial included abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting. These reactions were consistent with those reported in adult patients.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, were not adequately represented in clinical trials of mesalamine suppositories, making it difficult to ascertain whether they respond differently compared to younger patients. However, data from uncontrolled clinical studies and postmarketing reports indicate that this population may experience a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, when treated with mesalamine-containing products.

Due to these findings, it is essential to monitor complete blood cell counts and platelet counts in geriatric patients receiving mesalamine suppositories. Additionally, healthcare providers should consider the increased likelihood of diminished hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies, when prescribing mesalamine to elderly patients. These factors may necessitate careful dose adjustments and heightened vigilance during treatment.

Pregnancy

Limited published data on mesalamine use in pregnant women are insufficient to inform a drug-associated risk. Animal studies have shown no evidence of teratogenicity when mesalamine was administered orally to rats and rabbits during gestation at doses greater than the recommended human intra-rectal dose. Specifically, reproduction studies in rats at oral doses up to 320 mg/kg/day (approximately 1.7 times the recommended human intra-rectal dose) and in rabbits at doses up to 495 mg/kg/day (about 5.4 times the recommended human intra-rectal dose) during the period of organogenesis revealed no evidence of impaired fertility or harm to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. However, in the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2 to 4% and 15 to 20%, respectively. It is important to note that adverse outcomes in pregnancy can occur regardless of maternal health or medication use. Therefore, healthcare professionals should consider these factors when prescribing mesalamine to pregnant patients or women of childbearing potential.

Lactation

Limited published data on mesalamine use in nursing mothers are insufficient to inform a drug-associated risk. There is a potential for excretion of mesalamine in human breast milk. The effects of mesalamine on a breastfed infant or on milk production are unknown.

Renal Impairment

Patients with renal impairment or those taking nephrotoxic drugs should have their risks and benefits evaluated prior to treatment. It is essential to monitor renal function closely in these individuals. If there is any deterioration in renal function, mesalamine should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits associated with treatment. It is essential to assess liver function prior to initiating therapy and to monitor liver parameters throughout the course of treatment. Adjustments to dosage may be necessary based on the severity of liver impairment, and close monitoring of liver function tests is recommended to ensure patient safety.

Overdosage

In cases of mesalamine overdosage, it is important to recognize that while mesalamine absorption from the colon is limited, it is classified as an aminosalicylate. Symptoms indicative of salicylate toxicity may manifest, including nausea, vomiting, and abdominal pain. Additional symptoms can include tachypnea, hyperpnea, tinnitus, and various neurologic manifestations such as headache, dizziness, confusion, and seizures.

Severe salicylate intoxication can result in significant complications, including electrolyte and blood pH imbalances, which may lead to involvement of other organs, particularly the kidneys and liver.

Currently, there is no specific antidote available for mesalamine overdose. Therefore, management should focus on correcting fluid and electrolyte imbalances through the administration of appropriate intravenous therapy. It is also crucial to monitor and maintain adequate renal function throughout the treatment process.

Nonclinical Toxicology

Toxicology studies of mesalamine were conducted in rats, mice, rabbits, and dogs, with the kidney identified as the primary target organ of toxicity. In rats, adverse renal effects were noted following a single oral dose of 600 mg/kg, which is approximately 3.2 times the recommended human intra-rectal dose of mesalamine suppositories based on body surface area. Additionally, intravenous doses exceeding 214 mg/kg, about 1.2 times the recommended human intra-rectal dose, also resulted in renal toxicity.

In a 13-week oral gavage toxicity study in rats, papillary necrosis and/or multifocal tubular injury were observed in males receiving 160 mg/kg, approximately 0.86 times the recommended human intra-rectal dose, and in both males and females at 640 mg/kg, about 3.5 times the recommended dose. A combined 52-week toxicity and 127-week carcinogenicity study in rats revealed degeneration of the kidneys and hyalinization of basement membranes and Bowman's capsule at oral doses of 100 mg/kg/day, roughly 0.54 times the recommended human intra-rectal dose.

In a 14-day rectal toxicity study of mesalamine suppositories in rabbits, intra-rectal doses up to 800 mg/kg, approximately 8.6 times the recommended human intra-rectal dose, were not associated with any adverse effects. A six-month oral toxicity study in dogs indicated that doses of 80 mg/kg, about 1.4 times the recommended human intra-rectal dose, and higher resulted in renal pathology similar to that observed in rats. Furthermore, a rectal toxicity study in dogs demonstrated that a dose of 166.6 mg/kg, approximately 3 times the recommended human intra-rectal dose, led to chronic nephritis and pyelitis. In a 12-month eye toxicity study in dogs, keratoconjunctivitis sicca (KCS) was noted at oral doses of 40 mg/kg, about 0.72 times the recommended human intra-rectal dose, and above.

No teratogenic effects were reported in the studies. Mesalamine did not increase the incidence of neoplastic lesions over controls in a two-year study of Wistar rats fed up to 320 mg/kg/day, which is about 1.7 times the recommended human intra-rectal dose. Furthermore, mesalamine was not found to be mutagenic in the Ames test, the mouse lymphoma cell (TK +/-) forward mutation test, or the mouse micronucleus test. No effects on fertility or reproductive performance were observed in male and female rats at oral doses of mesalamine up to 320 mg/kg/day, approximately 1.7 times the recommended human intra-rectal dose.

Postmarketing Experience

Discoloration of urine to a reddish-brown hue has been reported in patients using mesalamine suppositories, particularly when urine comes into contact with surfaces or water treated with hypochlorite-containing bleach. Patients are advised to monitor their urine flow and to report any discoloration that occurs prior to contact with any surface or water, such as in the toilet.

Additionally, mesalamine suppositories have been associated with staining of surfaces that come into direct contact with the product. This includes, but is not limited to, fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. To prevent staining, it is recommended that mesalamine suppositories be kept away from these surfaces.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling (Patient Information) thoroughly to understand the proper use and potential effects of mesalamine suppositories. It is important to instruct patients not to cut or break the suppository, as this may affect its efficacy.

Patients should be informed to retain the suppository for one to three hours, or longer if possible, to ensure optimal absorption. Additionally, they should be encouraged to drink an adequate amount of fluids while using this medication.

In the event that a dose of mesalamine suppository is missed, patients should be instructed to administer it as soon as possible, unless it is almost time for the next scheduled dose. They must be cautioned against using two mesalamine suppositories simultaneously to compensate for a missed dose.

Patients may notice that their urine becomes discolored reddish-brown while using mesalamine suppositories, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. Healthcare providers should advise patients to monitor their urine flow and report any discoloration that occurs before contact with any surface or water, such as in the toilet.

Furthermore, it is essential to inform patients that mesalamine suppositories can stain surfaces that come into direct contact with them, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Patients should be instructed to keep mesalamine suppositories away from these surfaces to prevent staining.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product below 25°C (77°F), although refrigeration is permissible. Care should be taken to keep the product away from direct heat, light, and humidity to maintain its integrity and efficacy. Proper handling and storage conditions are crucial to ensure the product remains effective 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 Northstar Rx LLC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)