Mesalamine

Uses and Indications

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

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

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

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

It is important to instruct patients not to cut or break the suppository prior to administration. After insertion, patients should retain the suppository for one to three hours, or longer if possible, to maximize 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. Therefore, 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, aminosalicylates, or any components of the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Patients with renal impairment or those taking nephrotoxic drugs require careful evaluation of the risks and benefits associated with treatment. It is essential to monitor renal function in these individuals to ensure safety and efficacy.

In cases of mesalamine-induced acute intolerance syndrome, symptoms may closely resemble an exacerbation of ulcerative colitis. Healthcare professionals should monitor patients for any worsening of symptoms and discontinue treatment if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, necessitate immediate evaluation of the patient. If a hypersensitivity reaction is suspected, treatment should be discontinued promptly.

For patients with known liver impairment, a thorough assessment of the risks and benefits of treatment is crucial, as hepatic failure may occur.

General precautions should be taken regarding laboratory tests. Specifically, patients receiving mesalamine suppositories may exhibit spuriously elevated results in urinary normetanephrine tests when using liquid chromatography with electrochemical detection. Therefore, it is advisable to utilize an alternative, selective assay for normetanephrine to avoid misleading results.

Regular monitoring of renal function is recommended for patients with renal impairment or those on nephrotoxic medications. Additionally, due to the potential for spurious results, the use of an alternative, selective assay for normetanephrine is strongly advised.

Side Effects

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

Serious adverse reactions warrant particular attention. Patients with renal impairment or those taking nephrotoxic drugs should have their renal function monitored closely, as the risks and benefits of treatment must be carefully evaluated in these individuals. Additionally, mesalamine-induced acute intolerance syndrome may occur, with symptoms that can be challenging to differentiate from an exacerbation of ulcerative colitis. It is crucial to monitor for any worsening symptoms and to discontinue treatment if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of the medication if such reactions are suspected. Furthermore, patients with known liver impairment should also have their risks and benefits assessed, as hepatic failure has been reported.

Additional considerations include the potential for hypersensitivity to salicylates or aminosalicylates, as well as to any components of the formulation. Reports from uncontrolled clinical studies and postmarketing surveillance indicate a higher incidence of blood dyscrasias, such as agranulocytosis, neutropenia, and pancytopenia, particularly in patients aged 65 years and older. Therefore, it is recommended to monitor complete blood cell counts and platelet counts in elderly patients receiving 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 and observe for any mesalamine-related adverse reactions during co-administration.

When used 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.

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 have not been established in pediatric patients for the treatment of mildly to moderately active ulcerative proctitis. A clinical study evaluating the efficacy of mesalamine rectal suppositories in pediatric patients aged 5 to 17 years did not demonstrate efficacy. However, due to marketing exclusivity rights held by Forest Laboratories, LLC, this pediatric information is not included in the product labeling.

Geriatric Use

Clinical trials of mesalamine suppositories did not include a sufficient number of patients aged 65 and older to determine whether these elderly patients respond differently compared to younger patients. However, it is important to note that systemic exposures to mesalamine are increased in elderly subjects.

Reports from uncontrolled clinical studies and postmarketing surveillance have indicated a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in patients aged 65 years and older who are receiving mesalamine-containing products, such as mesalamine suppositories, compared to their younger counterparts.

Given these considerations, it is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine suppositories. Additionally, prescribers should take into account the greater frequency of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies, when prescribing mesalamine suppositories to geriatric patients.

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 2 to 4% and 15 to 20%, respectively. It is important to note that adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications. Therefore, healthcare professionals should consider these factors when prescribing mesalamine to pregnant patients or women of childbearing potential.

Lactation

Mesalamine and its N-acetyl metabolite are present in human milk in undetectable to small amounts. The concentration of mesalamine in milk has been reported to range from non-detectable to 0.11 mg/L, while the concentration of the N-acetyl-5-aminosalicylic acid metabolite ranges from 5 to 18.1 mg/L. Based on these concentrations, estimated infant daily dosages for an exclusively breastfed infant are 0 to 0.017 mg/kg/day of mesalamine and 0.75 to 2.72 mg/kg/day of N-acetyl-5-aminosalicylic acid.

There are limited reports of diarrhea in breastfed infants, and lactating mothers should monitor their breastfed infants for this adverse effect. However, there is no information available regarding the effects of mesalamine on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of mesalamine suppositories to an infant during lactation. Therefore, the developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for mesalamine suppositories and any potential adverse effects on the breastfed child from the drug or from the underlying maternal conditions. In published lactation studies, maternal mesalamine doses from various oral and rectal formulations ranged from 500 mg to 3 g daily.

Renal Impairment

Patients with renal impairment require careful evaluation of the risks and benefits associated with treatment. It is essential to monitor renal function in these individuals, particularly in those who are also taking nephrotoxic drugs. Dosing adjustments may be necessary based on the degree of renal impairment to ensure safety and efficacy.

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 is recommended to ensure patient safety and therapeutic efficacy.

Overdosage

In the event of an overdose with mesalamine suppository, it is important to note that there have been no documented reports of serious toxicity in humans resulting from massive overdosing. This suggests a favorable safety profile regarding acute overdosage.

Absorption Considerations

Under ordinary circumstances, the absorption of mesalamine from the colon is limited. This characteristic may contribute to the low incidence of serious adverse effects associated with overdose scenarios.

Recommended Actions

Healthcare professionals should monitor patients for any unusual symptoms following an overdose, although the likelihood of significant toxicity is low. Supportive care and symptomatic management should be the primary focus, as specific antidotes are not indicated for mesalamine overdose.

In summary, while the risk of serious toxicity from mesalamine suppository overdose appears minimal, vigilance and appropriate management remain essential in clinical practice.

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.

Non-teratogenic effects were observed in various studies. In a two-year study involving Wistar rats fed up to 320 mg/kg/day of mesalamine, there was no increase in the incidence of neoplastic lesions compared to controls. Mesalamine demonstrated no mutagenic potential in the Ames test, the mouse lymphoma cell (TK +/-) forward mutation test, or the mouse micronucleus test. Additionally, no effects on fertility or reproductive performance were noted in male and female rats at oral doses of mesalamine up to 320 mg/kg/day.

In terms of animal pharmacology and toxicology, adverse renal effects were noted in rats at a single oral dose of 600 mg/kg and at intravenous doses exceeding 214 mg/kg. A 13-week oral gavage toxicity study in rats revealed papillary necrosis and/or multifocal tubular injury in males receiving 160 mg/kg and in both sexes at 640 mg/kg. In a combined 52-week toxicity and 127-week carcinogenicity study, 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.

In a 14-day rectal toxicity study in rabbits, intra-rectal doses up to 800 mg/kg were not associated with any adverse effects. A six-month oral toxicity study in dogs indicated that doses of 80 mg/kg and higher caused renal pathology similar to that observed in rats. In a rectal toxicity study of mesalamine suppositories in dogs, a dose of 166.6 mg/kg resulted in chronic nephritis and pyelitis. Furthermore, in a 12-month eye toxicity study in dogs, keratoconjunctivitis sicca occurred at oral doses of 40 mg/kg and above.

Postmarketing Experience

No specific postmarketing experience details are available in the extracted data. As such, there are no additional adverse events or rare case reports to summarize.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling (Patient Information) thoroughly to understand the proper use and potential risks associated with 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 that they need to retain the suppository for one to three hours, or longer if possible, to ensure optimal absorption. In the event that a dose is missed, patients should administer the missed dose as soon as possible, unless it is nearly time for the next scheduled dose. They should be cautioned against using two mesalamine suppositories simultaneously to compensate for a missed dose.

Healthcare providers should also inform patients that mesalamine suppositories can cause staining of surfaces that come into direct contact with them, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Patients should be advised to keep the suppositories away from these surfaces to prevent staining.

It is essential to inform patients that mesalamine suppositories may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic medications, such as NSAIDs. Periodic monitoring of renal function will be conducted while patients are on therapy, and they should be encouraged to complete all blood tests ordered by their healthcare provider.

Patients should be made aware of the signs and symptoms of hypersensitivity reactions. They should be instructed to discontinue the use of mesalamine suppositories and report to their healthcare provider if they experience new or worsening symptoms of Acute Intolerance Syndrome, which may include cramping, abdominal pain, bloody diarrhea, fever, headache, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, healthcare providers should discuss the signs and symptoms of worsening liver function and advise them to report any such changes to their healthcare provider promptly.

Elderly patients and those taking azathioprine or 6-mercaptopurine should be informed about the risk of blood disorders associated with mesalamine therapy. They should be advised of the necessity for periodic monitoring of complete blood cell counts and platelet counts, and encouraged to complete all blood tests as directed by their healthcare provider.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at temperatures below 25ºC (77ºF) and may be refrigerated if necessary. Care should be taken to keep the product away from direct heat, light, and humidity to maintain its integrity and efficacy. Proper storage conditions are essential to ensure the product remains effective throughout its shelf life.

Additional Clinical Information

Patients should be advised to read the FDA-approved patient labeling for mesalamine suppositories. It is important not to cut or break the suppository and to retain it for one to three hours, or longer if possible. In the event of a missed dose, patients should administer the suppository as soon as possible, unless it is nearly time for the next dose; they should not use two suppositories simultaneously to compensate for a missed dose.

Clinicians should inform patients that mesalamine suppositories can stain direct contact surfaces, including fabrics and various materials, and should be kept away from these surfaces. Patients with known renal impairment or those taking nephrotoxic drugs, such as NSAIDs, should be made aware that mesalamine may decrease renal function, necessitating periodic monitoring of renal function. Patients should also be educated on the signs and symptoms of hypersensitivity reactions, including Acute Intolerance Syndrome, and instructed to report any new or worsening symptoms. Additionally, those with liver disease should be informed about the signs of worsening liver function. Elderly patients and those on azathioprine or 6-mercaptopurine should be monitored for blood disorders, with complete blood cell counts and platelet counts checked regularly as directed by their healthcare provider.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Mesalamine as submitted by Rising Pharma Holdings, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)