Mesalamine

Description

The active ingredient in Mesalamine suppositories, USP 1000 mg, is mesalamine, also known as mesalazine or 5-aminosalicylic acid (5-ASA). Mesalamine is chemically defined 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: There are no reported teratogenic or nonteratogenic effects associated with the use of mesalamine as per 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 support overall hydration. 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 the medication. This includes, but is not limited to, fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. It is advisable to keep mesalamine suppositories away from these surfaces to prevent 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

Healthcare professionals should carefully evaluate the risks and benefits of mesalamine treatment in patients with known renal impairment or those taking nephrotoxic medications. It is essential to monitor renal function closely, and mesalamine should be discontinued if there is any deterioration in renal status.

Patients may experience symptoms of mesalamine-induced acute intolerance syndrome, which can be challenging to differentiate from an exacerbation of ulcerative colitis. Therefore, it is crucial to monitor for any worsening of symptoms and to discontinue treatment if acute intolerance syndrome is suspected.

In cases where a hypersensitivity reaction is suspected, including conditions such as myocarditis and pericarditis, immediate evaluation of the patient is warranted, and mesalamine should be discontinued. Additionally, healthcare providers should assess the risks and benefits of mesalamine in patients with known liver impairment.

At the first signs or symptoms of severe cutaneous adverse reactions or any other indications of hypersensitivity, treatment should be discontinued, and further evaluation should be considered. Patients with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and utilize 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 complications.

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

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. 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 and require careful monitoring. Renal impairment is a significant concern; it is essential to evaluate the risks and benefits in patients with known renal impairment or those taking nephrotoxic drugs, and renal function should be 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, monitoring for worsening symptoms is crucial, 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 treatment if suspected. Hepatic failure is another serious concern, particularly in patients with known liver impairment, who should be carefully assessed for risks and benefits. Severe cutaneous adverse reactions require discontinuation of the medication at the first signs or symptoms, along with further evaluation for hypersensitivity. Patients should also be advised about photosensitivity, particularly those with pre-existing skin conditions, to avoid sun exposure and use protective measures.

Nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT); thus, ensuring adequate hydration during treatment is important. Furthermore, patients receiving mesalamine suppositories may experience spuriously elevated results in laboratory tests for urinary normetanephrine; alternative, selective assays should be used.

Additional considerations include known or suspected hypersensitivity to salicylates or aminosalicylates or to any ingredients in the formulation. Symptoms of overdosage may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication can lead to electrolyte and blood pH imbalances, potentially affecting other organs, including the kidneys and liver.

In pediatric patients, adverse reactions reported include abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting, which are similar to those observed in adult patients. In geriatric patients, there is a reported higher incidence of blood dyscrasias, such as agranulocytosis, neutropenia, and pancytopenia, compared to younger patients; therefore, monitoring of complete blood cell counts and platelet counts is recommended during treatment in this population.

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 agents.

The use of azathioprine or 6-mercaptopurine in conjunction with this medication may elevate the risk of blood disorders. Therefore, it is advised to monitor complete blood cell counts and platelet counts regularly 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 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. Among the participants, only 14 had histologically-confirmed cases of ulcerative proctitis.

Adverse reactions reported in pediatric patients during this trial included abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting. These reactions were consistent with those observed in adult patients. Caution is advised when considering the use of mesalamine suppositories in this population due to the lack of established efficacy and the potential for similar adverse effects.

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, reports from uncontrolled clinical studies and postmarketing surveillance 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 dose adjustments or heightened monitoring to ensure patient safety and therapeutic efficacy.

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 or rabbits during gestation at doses greater than the recommended human intra-rectal dose. Specifically, reproduction studies conducted 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 weigh the potential benefits and risks of mesalamine use in pregnant patients and consider individual circumstances when making treatment decisions.

Lactation

Limited published data on mesalamine use in nursing mothers are insufficient to inform a drug-associated risk. There is a potential for excretion in breast milk; however, the effects of mesalamine on the breastfed infant and on milk production are unknown. Caution should be exercised when administering mesalamine to a nursing woman.

Renal Impairment

Patients with renal impairment should be carefully evaluated for the risks and benefits of treatment, particularly if they are also taking nephrotoxic drugs. It is essential to monitor renal function regularly in these individuals. In cases where renal function deteriorates, mesalamine should be discontinued to prevent further complications.

Hepatic Impairment

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

No information is available regarding teratogenic effects associated with mesalamine.

Non-teratogenic effects were observed in studies where no adverse effects on fertility or reproductive performance were noted in male and female rats administered oral doses of mesalamine up to 320 mg/kg/day, which is approximately 1.7 times the recommended human intra-rectal dose based on body surface area.

In nonclinical toxicology studies, mesalamine did not result in an increased incidence of neoplastic lesions compared to controls in a two-year study involving Wistar rats fed up to 320 mg/kg/day of mesalamine mixed with their diet, also about 1.7 times the recommended human intra-rectal dose based on body surface area. Furthermore, mesalamine was found to be non-mutagenic in the Ames test, the mouse lymphoma cell (TK +/-) forward mutation test, and the mouse micronucleus test.

Toxicology studies conducted in rats, mice, rabbits, and dogs identified the kidney as the primary target organ for toxicity. In rats, adverse renal effects were noted at a single oral dose of 600 mg/kg, approximately 3.2 times the recommended human intra-rectal dose, and at intravenous doses exceeding 214 mg/kg, about 1.2 times the recommended human intra-rectal dose. A 13-week oral gavage toxicity study in rats revealed papillary necrosis and/or multifocal tubular injury in males receiving 160 mg/kg, about 0.86 times the recommended human intra-rectal dose, and in both sexes at 640 mg/kg, approximately 3.5 times the recommended human intra-rectal dose.

In a combined 52-week toxicity and 127-week carcinogenicity study in rats, degeneration of the kidneys and hyalinization of basement membranes and Bowman's capsule were observed at oral doses of 100 mg/kg/day and above, which is about 0.54 times the recommended human intra-rectal dose. A 14-day rectal toxicity study in rabbits indicated that 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.

In a six-month oral toxicity study in dogs, 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. 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. Additionally, in a 12-month eye toxicity study in dogs, keratoconjunctivitis sicca (KCS) was noted at oral doses of 40 mg/kg and above, which is about 0.72 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. If patients observe discolored urine, they should be advised to monitor their urine flow. However, they should report to their healthcare provider only if the urine is discolored upon leaving the body, prior to contact with any surface or water (e.g., in the toilet).

Furthermore, healthcare providers should inform patients that mesalamine suppositories can cause staining of surfaces that come into direct contact with the medication, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Patients should be advised 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 upon request. It should be stored at temperatures below 25°C (77°F) and may be refrigerated if necessary. Care should be taken to keep the product away from direct heat, light, and humidity to ensure 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 Zydus Pharmaceuticals USA Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)