Mesalamine

Description

Mesalamine Rectal Suspension Enema is a disposable unit containing 60 mL of a rectal suspension formulation. The active ingredient is mesalamine, also known as 5-aminosalicylic acid (5-ASA), which is chemically defined as 5-amino-2-hydroxybenzoic acid. The empirical formula of mesalamine is C₇H₇NO₃, with a molecular weight of 153.14. Each enema unit delivers 4 grams of mesalamine.

The formulation includes several inactive ingredients: carbomer 934P, edetate disodium, potassium acetate, potassium metabisulfite, purified water, and xanthan gum. Sodium benzoate is incorporated as a preservative. The enema unit features an applicator tip that is protected by a polyethylene cover and lubricated with USP white petrolatum. Additionally, the unit is designed with a one-way valve to prevent backflow of the dispensed product.

Uses and Indications

Mesalamine Rectal Suspension Enema is indicated for the treatment of active mild to moderate distal ulcerative colitis, proctosigmoiditis, or proctitis in adults.

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

Dosage and Administration

The recommended adult dosage of Mesalamine Rectal Suspension Enema is one rectal instillation (4 grams) in a 60 mL unit, administered once daily, preferably at bedtime. The enema should be retained for approximately eight hours to maximize therapeutic effect.

The usual course of therapy ranges from 3 to 6 weeks, tailored to the patient's symptoms and sigmoidoscopic findings. Mesalamine Rectal Suspension Enema is intended for rectal use only.

Prior to administration, patients should be instructed to shake the bottle well to ensure the suspension is homogeneous. The protective sheath from the applicator tip must be removed before use.

For optimal administration, patients are advised to assume a position lying on their left side, with the lower leg extended and the upper right leg flexed forward for balance. An alternative position is the knee-chest position. The applicator tip should be gently inserted into the rectum, directed toward the umbilicus. A steady squeezing of the bottle will facilitate the discharge of most of the preparation. It is important that the preparation is taken at bedtime, with the goal of retaining it throughout the night.

Contraindications

Mesalamine Rectal Suspension Enema is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, sulfites, or any other component of this medication. Use in these patients may lead to severe allergic reactions.

Warnings and Precautions

Mesalamine Rectal Suspension Enema contains potassium metabisulfite, which may lead to allergic-type reactions, including anaphylactic symptoms and potentially life-threatening or less severe asthmatic episodes in susceptible individuals. Healthcare professionals should be vigilant for signs of hypersensitivity reactions, particularly in patients with a history of sulfasalazine hypersensitivity, as similar reactions may occur with Mesalamine Rectal Suspension Enema or other mesalamine-containing compounds.

Hypersensitivity reactions associated with mesalamine can manifest as internal organ involvement, including myocarditis, pericarditis, nephritis, hepatitis, pneumonitis, and hematologic abnormalities. Immediate evaluation is warranted if any signs or symptoms of a hypersensitivity reaction arise. Should an alternative etiology for these symptoms not be established, Mesalamine Rectal Suspension Enema must be discontinued.

Renal impairment, including conditions such as minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been reported in patients treated with mesalamine or its derivatives. Therefore, it is essential to assess the risks and benefits of Mesalamine Rectal Suspension Enema in patients with known renal impairment, a history of renal disease, or those taking concomitant nephrotoxic medications. Given that mesalamine is primarily excreted by the kidneys, the risk of adverse reactions may be heightened in patients with impaired renal function. If renal function deteriorates during therapy, discontinuation of Mesalamine Rectal Suspension Enema is advised.

Additionally, mesalamine has been linked to an acute intolerance syndrome, which may be challenging to differentiate from a flare of inflammatory bowel disease. Symptoms of this syndrome include cramping, acute abdominal pain, bloody diarrhea, and may also present with fever, headache, and rash. If acute intolerance syndrome is suspected, treatment with Mesalamine Rectal Suspension Enema should be promptly discontinued.

It is recommended that renal function be evaluated in all patients prior to the initiation of Mesalamine Rectal Suspension Enema therapy and monitored periodically throughout treatment.

In cases of serious allergic reactions or emergencies, epinephrine is the preferred treatment, despite the presence of sodium or potassium metabisulfite in the injection, which carries its own potential risks.

Healthcare professionals should instruct patients to discontinue Mesalamine Rectal Suspension Enema if an alternative etiology for any signs or symptoms cannot be established, and to promptly stop treatment if acute intolerance syndrome is suspected.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most common clinical adverse experiences reported include abdominal pain, cramps, or discomfort (8.10%), headache (6.50%), gas or flatulence (6.13%), and nausea (5.77%). Other frequently observed reactions include flu-like symptoms (5.28%), tiredness or malaise (3.44%), fever (3.19%), and rash or spots (2.82%). Additional common reactions reported by participants include cold or sore throat (2.33%), diarrhea (2.09%), leg or joint pain (2.09%), dizziness (1.84%), and bloating (1.47%). Less frequently, patients may experience back pain (1.35%), pain on insertion of the enema tip (1.35%), hemorrhoids (1.35%), itching (1.23%), rectal pain (1.23%), constipation (0.98%), hair loss (0.86%), peripheral edema (0.61%), urinary tract infections or urinary burning (0.61%), and rectal pain, soreness, or burning (0.61%). Rarely, asthenia and insomnia have been reported (0.12% each).

In addition to these clinical experiences, postmarketing data have identified several serious adverse reactions. These include nephrotoxicity, pancreatitis, fibrosing alveolitis, elevated liver enzymes, nephrogenic diabetes insipidus, intracranial hypertension, nephrolithiasis, aplastic anemia, agranulocytosis, thrombocytopenia, eosinophilia, pancytopenia, neutropenia, oligospermia, infertility in men, anemia, leukocytosis, and thrombocytosis. Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have also been reported.

Warnings associated with treatment include the potential for hypersensitivity reactions, which may manifest as anaphylactic symptoms or less severe asthmatic episodes. Renal impairment, including minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been observed, particularly in patients with pre-existing conditions. Mesalamine-induced acute intolerance syndrome may present with cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. Hepatic failure has been reported in patients with pre-existing liver disease, and severe cutaneous adverse reactions necessitate discontinuation of treatment at the first signs or symptoms. Patients with pre-existing skin conditions may experience more severe photosensitivity reactions, and adequate hydration is advised to mitigate the risk of nephrolithiasis.

Additional considerations include urine discoloration, which may occur when mesalamine comes into contact with hypochlorite-containing bleach, and potential interference with laboratory tests, leading to spuriously elevated results for urinary normetanephrine. There is also an increased risk of nephrotoxicity when used in conjunction with nephrotoxic agents, as well as blood disorders when combined with azathioprine or 6-mercaptopurine.

Drug Interactions

The concurrent administration of mesalamine with nephrotoxic agents, particularly non-steroidal anti-inflammatory drugs (NSAIDs), may elevate the risk of nephrotoxicity. It is advisable to monitor patients receiving these combinations for any alterations in renal function as well as for mesalamine-related adverse reactions.

Additionally, the use of mesalamine in conjunction with azathioprine or 6-mercaptopurine, as well as other myelotoxic agents, may heighten the risk of blood disorders, bone marrow failure, and related complications. In instances where the concomitant use of mesalamine and these myelotoxic drugs is necessary, it is recommended to conduct regular blood tests, including complete blood cell counts and platelet counts, to ensure patient safety.

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 the lack of pediatric-specific studies when prescribing this medication to younger patients.

Geriatric Use

Clinical trials of Mesalamine Rectal Suspension Enema 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 indicate a higher incidence of blood dyscrasias, such as agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine-containing products, including Mesalamine Rectal Suspension Enema. This increased risk may be associated with factors such as ulcerative colitis, the use of interacting drugs, or reduced renal function.

Given these considerations, it is advisable to monitor complete blood cell counts and platelet counts in elderly patients during treatment with Mesalamine Rectal Suspension Enema, particularly if the patient is also receiving anticoagulants. Additionally, when prescribing this medication to geriatric patients, healthcare providers should take into account the higher likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies.

Pregnancy

Teratologic studies conducted in rats and rabbits at oral doses up to five and eight times, respectively, the maximum recommended human dose have shown no evidence of harm to the embryo or fetus. However, there are no adequate and well-controlled studies in pregnant women for either sulfasalazine or 5-ASA. Given that animal reproduction studies are not always predictive of human response, 5-ASA should be used during pregnancy only if clearly needed. Healthcare professionals are advised to weigh the potential benefits against the risks when considering the use of this medication in pregnant patients.

Lactation

It is not known whether mesalamine or its metabolite(s) are excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug, as many drugs are excreted in human milk. Therefore, healthcare professionals should consider the potential risks and benefits when advising lactating mothers regarding the use of mesalamine.

Renal Impairment

Patients with renal impairment, including conditions such as minimal change disease, acute and chronic interstitial nephritis, and renal failure, have been reported to experience adverse effects when treated with products containing mesalamine or those converted to mesalamine. Given that mesalamine is substantially excreted by the kidneys, the risk of adverse reactions may be heightened in patients with reduced kidney function.

It is essential to evaluate the risks and benefits of using Mesalamine Rectal Suspension Enema in patients with known renal impairment, a history of renal disease, or those taking concomitant nephrotoxic medications. Prior to initiating therapy, renal function should be assessed in all patients, and ongoing monitoring is recommended throughout the course of treatment. If there is any deterioration in renal function while on Mesalamine Rectal Suspension Enema, the therapy should be discontinued.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the prescribing information.

Overdosage

In cases of mesalamine overdose, it is important to recognize that while mesalamine absorption from the colon is limited, the use of Mesalamine Rectal Suspension Enema can still lead to significant toxicity. Symptoms of salicylate toxicity may manifest as nausea, vomiting, and abdominal pain, along with respiratory symptoms such as tachypnea and hyperpnea. Neurologic symptoms, including headache, dizziness, confusion, and seizures, may also occur.

Severe salicylate intoxication can result in serious complications, including electrolyte and blood pH imbalances, which may further lead to involvement of other organs, such as 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. Healthcare professionals should remain vigilant for the development of any severe symptoms and manage them accordingly.

Nonclinical Toxicology

Mesalamine was evaluated for its potential carcinogenic effects in a two-year study involving Wistar rats. The results indicated no increase in the incidence of neoplastic lesions when compared to control groups, with subjects receiving doses of up to 320 mg/kg/day of mesalamine mixed with their diet.

In terms of mutagenicity, mesalamine demonstrated no mutagenic effects in various Salmonella typhimurium tester strains, including TA98, TA100, TA1535, TA1537, and TA1538. Additionally, no reverse mutations were observed in assays utilizing the E. coli strain WP2UVRA. An in vivo mouse micronucleus assay conducted at a dose of 600 mg/kg also showed no effects, and a sister chromatid exchange assay at doses up to 610 mg/kg yielded similar results, indicating a lack of mutagenic potential.

Regarding reproductive toxicity, no adverse effects on fertility were noted in rats administered doses of up to 320 mg/kg/day. It is important to mention that while oligospermia and infertility have been very rarely reported in men treated with sulfasalazine, such effects have not been associated with mesalamine treatment.

Postmarketing Experience

During post-approval use of mesalamine, various adverse reactions have been identified. These reactions are reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Renal disorders have been noted, along with additional adverse events associated with products containing or metabolized to mesalamine. These include nephrotoxicity, pancreatitis, fibrosing alveolitis, elevated liver enzymes, nephrogenic diabetes insipidus, intracranial hypertension, and nephrolithiasis. Notably, cases of pancreatitis and fibrosing alveolitis have also been reported as manifestations of inflammatory bowel disease.

Published case reports and spontaneous postmarketing surveillance have documented rare instances of aplastic anemia, agranulocytosis, thrombocytopenia, eosinophilia, pancytopenia, neutropenia, oligospermia, and infertility in men. Additionally, anemia, leukocytosis, and thrombocytosis may present as part of the clinical picture of inflammatory bowel disease.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported, as well as cases of pleurisy and pleuritis.

Mild hair loss, characterized by "more hair in the comb," was observed in 7 of 815 patients treated with mesalamine, with no instances reported in the placebo group. The literature also includes at least six additional patients experiencing mild hair loss while receiving either mesalamine or sulfasalazine. It is noted that retreatment does not always lead to repeated hair loss.

Patient Counseling

Patients should be informed that while using Mesalamine Rectal Suspension Enema, their urine may become discolored reddish-brown if it comes into contact with surfaces or water treated with hypochlorite-containing bleach. They should be advised to monitor their urine flow and report any discoloration that occurs upon leaving the body, prior to contact with any surface or water, to their healthcare provider.

It is important to counsel patients with pre-existing skin conditions, such as atopic dermatitis and atopic eczema, that they may experience more severe photosensitivity reactions. They should be advised to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors.

Patients should be reminded to maintain adequate hydration throughout their treatment.

Instructions for the administration of the enema should be clearly communicated. Patients should be instructed to shake the bottle well to ensure the suspension is homogeneous. They should remove the protective sheath from the applicator tip and be informed that holding the bottle at the neck will not cause any of the medication to be discharged. The recommended position for administration is lying on the left side, with the lower leg extended and the upper right leg flexed forward for balance, although the knee-chest position is also acceptable. The applicator tip should be gently inserted into the rectum, pointing toward the umbilicus, and a steady squeezing of the bottle will discharge most of the preparation. Patients should be advised to take the preparation at bedtime with the goal of retaining it throughout the night. Patient instructions are provided with every seven units.

Additionally, patients should be made aware that Mesalamine Rectal Suspension Enema can stain surfaces that come into direct contact with it, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. They should take care in selecting a suitable location for the administration of this product.

Storage and Handling

Mesalamine Rectal Suspension Enema is supplied in a foil-wrapped unit containing seven bottles. The product should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F). Temporary excursions outside this temperature range are permitted; please refer to the current United States Pharmacopeia (USP) for guidance.

Once the foil-wrapped unit is opened, all enemas should be used promptly as directed by a physician. It is important to note that the contents of enemas removed from the foil pouch may darken over time. While slight darkening does not affect the potency of the product, enemas with dark brown contents should be discarded.

Care should be taken during administration, as Mesalamine Rectal Suspension Enema may stain surfaces that come into direct contact with it, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Therefore, a suitable location for administration should be chosen to prevent staining.

Additional Clinical Information

The use of mesalamine may interfere with laboratory tests, specifically leading to spuriously elevated results for urinary normetanephrine when measured by liquid chromatography with electrochemical detection. This is due to the similarity in chromatograms between normetanephrine and mesalamine’s main metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Clinicians should consider utilizing an alternative, selective assay for normetanephrine.

Mesalamine Rectal Suspension Enema is intended for rectal use only. Patients should be informed that their urine may appear discolored reddish-brown when in contact with hypochlorite-containing bleach, and they should monitor their urine flow, reporting any discoloration that occurs before contact with surfaces or water. Additionally, patients with pre-existing skin conditions, such as atopic dermatitis and eczema, may experience heightened photosensitivity and should take precautions against sun exposure. Adequate hydration during treatment is also advised.

Postmarketing experience has revealed several adverse reactions associated with mesalamine, including nephrotoxicity, pancreatitis, fibrosing alveolitis, elevated liver enzymes, nephrogenic diabetes insipidus, intracranial hypertension, and nephrolithiasis. Rare cases of aplastic anemia, agranulocytosis, thrombocytopenia, eosinophilia, pancytopenia, neutropenia, oligospermia, and infertility in men have been reported. Anemia, leukocytosis, and thrombocytosis may also present in patients with inflammatory bowel disease. Furthermore, severe cutaneous adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), as well as pleurisy/pleuritis, have been documented in postmarketing cases.

FDA Insert (PDF)

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

View full prescribing information (PDF)