Mesalamine

Description

Each mesalamine extended-release capsule, USP contains 0.375 g of mesalamine, USP (5-aminosalicylic acid, 5-ASA), an aminosalicylate. The molecular weight of mesalamine is 153.14 g/mol, and its molecular formula is C7H7NO3. The capsules contain pellets composed of mesalamine in a polymer matrix with an enteric coating that dissolves at pH 6 and above.

The inactive ingredients of mesalamine extended-release capsules, USP include colloidal silicon dioxide, ethyl acrylate and methyl methacrylate copolymer dispersion, hypromellose, magnesium stearate, methacrylic acid and methyl methacrylate copolymer (1:1), microcrystalline cellulose, simethicone emulsion 30%, talc, titanium dioxide, and triethyl citrate. The capsule shell is made of gelatin, iron oxide red, iron oxide yellow, sodium lauryl sulfate, and titanium dioxide. The capsule shells are imprinted with edible black ink, which contains black iron oxide, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution.

Uses and Indications

Mesalamine extended-release capsules are indicated for the maintenance of remission of ulcerative colitis in adults.

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

Dosage and Administration

The recommended dosage of mesalamine extended-release capsules is 1.5 g, which corresponds to four 0.375 g capsules, administered once daily in the morning.

Prior to initiating therapy, healthcare professionals should evaluate the patient's renal function. It is essential that the capsules be swallowed whole; they must not be cut, broken, crushed, or chewed to ensure proper release and absorption of the medication. Co-administration with antacids should be avoided to prevent potential interactions. Patients are advised to drink an adequate amount of fluids while on this medication. Mesalamine extended-release capsules can be taken without regard to meals, allowing for flexibility in administration.

Contraindications

Use of mesalamine extended-release capsules is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or any component 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 treatment and monitored periodically throughout the course of therapy. In patients with known renal impairment or those taking nephrotoxic medications, a careful evaluation of the risks and benefits is essential. If there is any deterioration in renal function, treatment must be discontinued.

Healthcare professionals should be vigilant for symptoms of Mesalamine-Induced Acute Intolerance Syndrome, which may mimic an exacerbation of ulcerative colitis. Close monitoring for worsening symptoms is advised, and treatment should be halted if acute intolerance syndrome is suspected.

Hypersensitivity reactions, including myocarditis and pericarditis, require immediate evaluation. If a hypersensitivity reaction is suspected, discontinuation of the medication is necessary. Additionally, in patients with known liver impairment, a thorough assessment of the risks and benefits should be conducted prior to treatment initiation.

Severe cutaneous adverse reactions can occur; therefore, treatment should be discontinued at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation may be warranted in these cases.

Patients should be informed about the risk of photosensitivity. Those with pre-existing skin conditions are advised to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors.

Nephrolithiasis is a potential risk, as mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). It is crucial to ensure adequate fluid intake during treatment to mitigate this risk.

In terms of laboratory considerations, the use of mesalamine may interfere with certain laboratory tests, specifically leading to spuriously elevated results when measuring urinary normetanephrine via liquid chromatography with electrochemical detection. Regular monitoring of renal function is recommended throughout the treatment period to ensure patient safety.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most common adverse reactions, occurring in 3% or more of participants, include headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis.

Serious adverse reactions warrant careful monitoring and evaluation. Patients with known renal impairment or those taking nephrotoxic drugs should have their renal function assessed at the beginning of treatment and periodically thereafter. It is crucial to evaluate the risks and benefits of treatment in these patients and to discontinue therapy 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 essential, and treatment should be discontinued if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, require immediate evaluation and discontinuation of treatment if suspected. Patients with known liver impairment should also be carefully evaluated for the risks and benefits of therapy, as hepatic failure has been reported. Severe cutaneous adverse reactions necessitate discontinuation at the first signs or symptoms, along with consideration for further evaluation.

Patients should be advised about the risk of nephrolithiasis, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). To mitigate this risk, it is important to ensure adequate fluid intake during treatment. Furthermore, patients with pre-existing skin conditions should be cautioned about photosensitivity and advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

It is also important to note that the use of mesalamine may interfere with laboratory tests, leading to spuriously elevated results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection.

Patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or any component of mesalamine extended-release capsules should not receive this treatment. Symptoms of salicylate toxicity, which may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (such as headache, dizziness, confusion, and seizures), should be monitored closely. Severe salicylate intoxication can lead to electrolyte and blood pH imbalances, potentially resulting in damage to other organs, including the kidneys and liver.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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

No pediatric use information is provided in the text.

Geriatric Use

Elderly patients may be at an increased risk for renal impairment, necessitating careful evaluation of renal function prior to the initiation of mesalamine extended-release capsules therapy. It is recommended that renal function be assessed periodically throughout the course of treatment.

For geriatric patients with known renal impairment, a history of renal disease, or those who are concurrently taking nephrotoxic medications, close monitoring for any decline in renal function and potential mesalamine-related adverse reactions is essential.

In the event that renal function deteriorates during therapy, mesalamine extended-release capsules should be discontinued to mitigate the risk of further complications.

Pregnancy

Published data from meta-analyses, cohort studies, and case series regarding the use of mesalamine during pregnancy have not consistently demonstrated an association with major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.7 and 5.4 times, respectively, the maximum recommended human dose did not result in adverse developmental outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown. It is important to note that adverse outcomes in pregnancy can occur regardless of maternal health or medication use. 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.

In women with ulcerative colitis, published data suggest that increased disease activity is associated with a higher risk of adverse pregnancy outcomes, which may include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g), and small for gestational age infants at birth. There is no clear evidence indicating that mesalamine exposure during early pregnancy is linked to an increased risk of major congenital malformations, including cardiac malformations.

However, it is essential to recognize that published epidemiologic studies have significant methodological limitations that complicate data interpretation. These limitations include the inability to control for confounding factors such as underlying maternal disease and concomitant medication use, as well as gaps in information regarding the dose and duration of mesalamine use.

Given these considerations, healthcare professionals should weigh the potential benefits of mesalamine treatment against the risks, particularly in pregnant patients or those planning to become pregnant.

Lactation

There is limited information regarding the excretion of mesalamine extended-release capsules in human breast milk. The safety and effectiveness of mesalamine in pediatric patients, including breastfed infants, have not been established. Therefore, lactating mothers should exercise caution when considering the use of mesalamine while breastfeeding. It is advisable for healthcare professionals to weigh the potential benefits against any unknown risks to the nursing infant.

Renal Impairment

Renal function should be assessed at the beginning of treatment and periodically throughout the course of therapy in patients with renal impairment. It is essential to evaluate the risks and benefits of treatment in patients with known renal impairment or those taking nephrotoxic drugs, with close monitoring of renal function. If there is any deterioration in renal function, discontinuation of the treatment is recommended.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of treatment. It is essential to consider the degree of liver function compromise when determining the appropriateness of therapy. Monitoring of liver function is recommended to ensure patient safety and to adjust treatment as necessary. Specific dosage modifications may be required based on the severity of hepatic impairment, and healthcare providers should remain vigilant in assessing any potential adverse effects related to liver function during the course of treatment.

Overdosage

In cases of mesalamine overdosage, healthcare professionals should be vigilant for symptoms indicative of salicylate toxicity. These symptoms may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, headache, dizziness, confusion, and seizures. The presence of these symptoms necessitates immediate medical evaluation and intervention.

Severe salicylate intoxication can result in significant complications, including electrolyte and blood pH imbalances, which may lead to renal and liver damage. Therefore, it is crucial to monitor the patient's vital signs and laboratory parameters closely.

There is currently no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may provide beneficial effects in managing acute overdosage. Healthcare providers should consider gastrointestinal tract decontamination to prevent further absorption of the drug in cases of overdose. This may involve the administration of activated charcoal, provided that the patient is alert and able to protect their airway.

Management of fluid and electrolyte imbalances is essential. Appropriate intravenous therapy should be initiated to correct these imbalances and to maintain adequate renal function during the treatment of an overdose. Given that mesalamine is a pH-dependent delayed-release product, this characteristic should be taken into account when formulating a treatment plan for suspected overdose cases.

In summary, prompt recognition of symptoms, appropriate decontamination, and supportive care are critical components in the management of mesalamine overdosage.

Nonclinical Toxicology

Nonclinical studies have evaluated the potential effects of mesalamine on reproductive performance and carcinogenicity. No effects on fertility or reproductive performance were observed in male and female rats administered oral mesalamine at doses up to 320 mg/kg, which is approximately 1.7 times the recommended human dose based on body surface area.

In terms of carcinogenicity, dietary mesalamine was not found to be carcinogenic in rats at doses as high as 480 mg/kg/day, nor in mice at 2,000 mg/kg/day. These doses correspond to about 2.6 and 5.4 times the recommended human dose of granulated mesalamine capsules of 1.5 g/day, respectively, when calculated based on body surface area. Additionally, mesalamine demonstrated a negative result in several genotoxicity assays, including the Ames test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, the sister chromatid exchange assay in Chinese hamster bone marrow, and the mouse bone marrow micronucleus test.

Animal studies, including 13-week and 26-week oral toxicity studies in rats, as well as 26-week and 52-week oral toxicity studies in dogs, identified the kidney as the primary target organ for mesalamine toxicity. Lethal doses of mesalamine were observed in mice and rats, with single oral doses of 800 mg/kg (approximately 2.2 times the recommended human dose based on body surface area) and 1,800 mg/kg (approximately 9.7 times the recommended human dose) resulting in gastrointestinal and renal toxicity.

At lower oral doses, minimal to slight tubular injury was noted at 40 mg/kg/day (about 0.20 times the human dose based on body surface area), while doses of 160 mg/kg/day (approximately 0.90 times the human dose) or higher in rats led to renal lesions, including tubular degeneration, tubular mineralization, and papillary necrosis. Similarly, oral doses of 60 mg/kg/day (about 1.1 times the human dose) or higher in dogs resulted in renal lesions characterized by tubular atrophy, interstitial cell infiltration, chronic nephritis, and papillary necrosis.

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 report at this time.

Patient Counseling

Healthcare providers should advise patients to swallow mesalamine extended-release capsules whole and to avoid cutting, breaking, crushing, or chewing the capsules. It is important to inform patients to refrain from co-administering these capsules with antacids and to ensure they drink an adequate amount of fluids during treatment.

Patients may take mesalamine extended-release capsules without regard to meals. They should be made aware that their urine may become discolored reddish-brown when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. If patients observe discolored urine, they should monitor their urine flow and report to their healthcare provider only if the urine is discolored upon leaving the body, prior to contact with any surface or water.

Healthcare providers should inform patients that mesalamine extended-release capsules may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic drugs, including NSAIDs. Periodic monitoring of renal function will be conducted during therapy, and patients should be advised to complete all blood tests ordered by their healthcare provider.

Patients should be educated on the signs and symptoms of hypersensitivity reactions. They must be instructed to discontinue the use of mesalamine extended-release capsules 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 inform them of the signs and symptoms of worsening liver function and advise them to report any such signs or symptoms to their healthcare provider. Additionally, patients should be made aware of 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 a severe cutaneous adverse reaction or any other sign 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. Furthermore, healthcare providers should instruct patients to drink an adequate amount of fluids during treatment to minimize the risk of kidney stone formation and 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.

Finally, 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. Patients should be encouraged to complete all blood tests ordered by their healthcare provider.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20° to 25°C (68° to 77°F). Temporary excursions are permissible between 15° and 30°C (59° and 86°F), in accordance with USP Controlled Room Temperature guidelines. Proper container requirements and special handling needs should be adhered to in order to maintain product integrity.

Additional Clinical Information

The use of mesalamine extended-release capsules may result in spuriously elevated urinary normetanephrine test results due to the similarity in chromatograms between normetanephrine and mesalamine's main metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Clinicians are advised to consider alternative, selective assays for accurate measurement of normetanephrine.

Patients should be counseled to avoid sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors to minimize the risk of photosensitivity reactions.

FDA Insert (PDF)

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

View full prescribing information (PDF)