Pentasa

Description

PENTASA (mesalamine) is an extended-release formulation intended for oral administration, serving as an aminosalicylate anti-inflammatory agent for gastrointestinal use. Mesalamine, chemically known as 5-amino-2-hydroxybenzoic acid, has a molecular weight of 153.14.

The 250 mg capsule contains 250 mg of mesalamine along with inactive ingredients, which include acetylated monoglyceride, castor oil, colloidal silicon dioxide, ethylcellulose, hydroxypropyl methylcellulose, starch, stearic acid, sugar, talc, and white wax. The capsule shell is composed of D&C Yellow #10, FD&C Blue #1, FD&C Green #3, gelatin, titanium dioxide, and other components.

The 500 mg capsule contains 500 mg of mesalamine and shares a similar composition of inactive ingredients, including acetylated monoglyceride, castor oil, colloidal silicon dioxide, ethylcellulose, hydroxypropyl methylcellulose, starch, stearic acid, sugar, talc, and white wax. The capsule shell for this formulation includes FD&C Blue #1, gelatin, titanium dioxide, and additional ingredients.

Uses and Indications

PENTASA is indicated for the induction of remission and for the treatment of mildly to moderately active ulcerative colitis in adult patients.

There are no teratogenic or nonteratogenic effects associated with PENTASA.

Dosage and Administration

The recommended dosage for the medication is 1 g administered orally four times daily. Healthcare professionals should instruct patients to swallow the capsules whole, ensuring they are not crushed or chewed to maintain the integrity of the formulation.

As an alternative, the capsule(s) may be opened, and the contents can be sprinkled onto a small amount of applesauce or yogurt for easier administration. It is essential to advise patients to consume an adequate amount of fluids while taking this medication to facilitate proper absorption and minimize gastrointestinal discomfort.

Contraindications

Use of PENTASA is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, as well as to any of the product's ingredients. 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 with PENTASA and monitored periodically throughout the course of therapy. It is crucial to evaluate the risks and benefits of PENTASA in patients with known renal impairment or those receiving nephrotoxic medications. Should renal function deteriorate during treatment, PENTASA must be discontinued.

Healthcare professionals should be vigilant for signs of Mesalamine-Induced Acute Intolerance Syndrome, which may present as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. If such symptoms are suspected, treatment should be discontinued immediately.

Hypersensitivity reactions, including myocarditis and pericarditis, necessitate the cessation of PENTASA if any signs of hypersensitivity are observed. Additionally, in patients with known liver impairment, a careful assessment of the risks and benefits of PENTASA is recommended prior to initiation.

Severe cutaneous adverse reactions may occur; therefore, treatment should be stopped at the first indication of such reactions or any other signs of hypersensitivity, and further evaluation should be considered. Patients are also advised to avoid sun exposure if they have pre-existing skin conditions, as photosensitivity may be exacerbated.

Cases of nephrolithiasis have been reported in patients using mesalamine. It is important to note that mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). To mitigate this risk, adequate hydration should be maintained during treatment.

Healthcare professionals should be aware that mesalamine may interfere with laboratory tests, specifically leading to elevated urinary normetanephrine test results. Regular assessment of renal function is essential at the beginning of treatment and periodically thereafter to ensure patient safety.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in 1% to 3% of participants, include diarrhea (3%), abdominal distention, nausea (2%), vomiting (2%), headache (2%), abdominal pain (2%), dyspepsia (2%), and rash (1%).

Serious adverse reactions have also been reported. These include blood and lymphatic system disorders such as thrombocythemia and thrombocytopenia. Cardiac disorders may manifest as palpitations, pericarditis, vasodilation, chest pain, fatal myocarditis, and T-wave abnormalities. Gastrointestinal disorders can include severe conditions such as duodenal ulcers, GI bleeding, pancreatitis, and fecal incontinence, among others.

General disorders such as fever and malaise have been noted, alongside infections and infestations like oral moniliasis and conjunctivitis. Investigations have shown increases in various laboratory parameters, including GGTP, alkaline phosphatase, LDH, SGOT, SGPT, lipase, and amylase.

Metabolism and nutritional disorders may present as anorexia, edema, and increased thirst. Musculoskeletal and connective tissue disorders include arthralgia, leg cramps, and myalgia. Nervous system disorders reported are dizziness, insomnia, somnolence, paresthesia, and intracranial hypertension. Psychiatric disorders such as depression and asthenia have also been observed.

Renal and urinary disorders can be significant, with reports of albuminuria, hematuria, urinary frequency, acute and chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, and nephrotic syndrome. Reproductive system and breast disorders may include amenorrhea, breast pain, hypomenorrhea, menorrhagia, metrorrhagia, and reversible oligospermia.

Respiratory, thoracic, and mediastinal disorders have been noted, including pulmonary infiltrates, dyspnea, interstitial lung disease, pleurisy/pleuritis, and pneumonitis. Skin and subcutaneous tissue disorders can range from acne and alopecia to more severe conditions such as DRESS, SJS/TEN, and other severe cutaneous adverse reactions.

Warnings associated with treatment include the potential for mesalamine-induced acute intolerance syndrome, which necessitates discontinuation if symptoms such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, or rash occur. Hypersensitivity reactions, including myocarditis and pericarditis, require immediate cessation of therapy. Additionally, hepatic failure should be carefully evaluated in patients with known liver impairment, and nephrolithiasis has been reported, emphasizing the need for adequate hydration during treatment.

Drug Interactions

The concomitant use of nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs), may lead to an increased risk of nephrotoxicity. It is recommended to monitor renal function closely and observe for any mesalamine-related adverse reactions in patients receiving these medications.

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

Packaging & NDC

The table below lists all NDC Code configurations of Pentasa (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 potential risks and benefits before prescribing this medication to pediatric patients.

Geriatric Use

Clinical trials of PENTASA 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, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine-containing products such as PENTASA compared to younger adults. This increased risk may be associated with factors such as ulcerative colitis, the use of interacting drugs, or reduced renal function.

It is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with PENTASA. Additionally, when prescribing PENTASA to patients aged 65 years and older, healthcare providers should consider the greater frequency of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies that may affect treatment outcomes.

Pregnancy

Published data from meta-analyses, cohort studies, and case series regarding the use of mesalamine during pregnancy have not consistently demonstrated an association between mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, it is important to note that adverse effects on maternal and fetal outcomes are associated with ulcerative colitis during pregnancy.

In animal reproduction studies, oral administration of mesalamine during organogenesis in pregnant rats at doses up to 1000 mg/kg/day (approximately 2.4 times the maximum recommended human dose of 4 g/day, based on body surface area comparison) and in rabbits at doses of 800 mg/kg/day (approximately 3.9 times the maximum recommended human dose) revealed no evidence of adverse developmental effects.

The background risk of major birth defects and miscarriage for the indicated populations remains unknown, as all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

In women with ulcerative colitis, increased disease activity has been associated with a higher risk of adverse pregnancy outcomes, including preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g), and small for gestational age at birth.

While published data suggest that mesalamine exposure during early pregnancy (first trimester) and throughout pregnancy does not correlate with an increased risk of major congenital malformations, including cardiac malformations, the epidemiologic studies available have significant methodological limitations. These limitations include the inability to control for confounders such as underlying maternal disease, concomitant medication use, and incomplete information regarding the dose and duration of mesalamine use.

Healthcare professionals should consider these factors when prescribing mesalamine to pregnant patients and remain vigilant regarding the management of ulcerative colitis to mitigate potential risks associated with disease activity during pregnancy.

Lactation

Data from published literature indicate that mesalamine and its metabolite, N-acetyl-5-aminosalicylic acid, are present in human milk in small amounts, with relative infant doses (RID) of 0.1% or less for mesalamine. There have been case reports of diarrhea observed in breastfed infants exposed to mesalamine. However, there is no information available regarding the effects of mesalamine on milk production.

Due to the lack of clinical data during lactation, a clear determination of the risk of PENTASA to an infant during breastfeeding cannot be made. Therefore, healthcare professionals should consider the developmental and health benefits of breastfeeding alongside the mother’s clinical need for PENTASA and any potential adverse effects on the breastfed child from PENTASA or from the underlying maternal condition.

Renal Impairment

Mesalamine is substantially excreted by the kidneys, which increases the risk of toxic reactions in patients with impaired renal function. It is essential to evaluate renal function in all patients prior to the initiation of PENTASA therapy and to monitor it periodically during treatment. Special attention should be given to patients with known renal impairment, a history of renal disease, or those taking nephrotoxic drugs, as they may be at higher risk for decreased renal function and mesalamine-related adverse reactions.

Renal function should be assessed at the beginning of treatment and periodically thereafter. If there is any deterioration in renal function while on therapy, PENTASA should be discontinued. The risks and benefits of continuing PENTASA therapy in patients with known renal impairment or those taking nephrotoxic medications must be carefully evaluated.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using PENTASA. Due to the potential for altered pharmacokinetics in this population, it is essential to consider the degree of liver function compromise when prescribing this medication. Monitoring of liver function tests may be warranted to ensure patient safety and to assess the need for any dosage adjustments. Clinicians are advised to exercise caution and to tailor treatment plans based on individual patient assessments and ongoing evaluations of liver health.

Overdosage

In the event of an overdose of PENTASA, which is classified as an aminosalicylate, healthcare professionals should be vigilant for symptoms indicative of salicylate toxicity. These symptoms may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and various neurologic manifestations such as headache, dizziness, confusion, and seizures. It is important to note that severe intoxication can result in significant electrolyte and blood pH imbalances, potentially leading to damage to vital organs, including the kidneys and liver.

Management of mesalamine overdose does not involve a specific antidote; however, conventional treatment strategies for salicylate toxicity may be employed. Initial steps should focus on gastrointestinal decontamination to minimize further absorption of the drug. This may include the use of activated charcoal, provided that the patient presents within an appropriate time frame post-ingestion.

Additionally, it is crucial to address any fluid and electrolyte imbalances that may arise as a result of the overdose. The administration of appropriate intravenous therapy is recommended to restore balance and ensure adequate renal function is maintained throughout the management process. Continuous monitoring of the patient's clinical status and laboratory parameters is essential to guide further therapeutic interventions.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. Additionally, no effects on fertility or reproductive performance were noted in male or female rats administered oral doses of mesalamine up to 400 mg/kg/day, which is approximately 0.8 times the maximum recommended human dose based on body surface area.

In a 104-week dietary carcinogenicity study involving CD-1 mice, mesalamine was administered at doses up to 2500 mg/kg/day, with no evidence of tumorigenicity. This dose corresponds to approximately 2.5 times the maximum recommended human dose on a body surface area basis. Similarly, in a 104-week dietary carcinogenicity study in Wistar rats, mesalamine at doses up to 800 mg/kg/day also showed no tumorigenic effects, representing about 1.5 times the maximum recommended human dose on a body surface area basis.

Furthermore, no evidence of mutagenicity was detected in both an in vitro Ames test and an in vivo mouse micronucleus test.

Postmarketing Experience

During post-approval use of mesalamine, various adverse reactions have been reported voluntarily or through surveillance programs. Due to the nature of these reports, which originate from a population of uncertain size, it is not always feasible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders have included chest pain, fatal myocarditis, pericarditis, and T-wave abnormalities.

Hematologic Disorders reported include agranulocytosis, anemia, aplastic anemia, leukopenia, and pancytopenia.

Hepatic Disorders have encompassed cirrhosis, jaundice (including cholestatic jaundice), hepatotoxicity, hepatitis, and possible hepatocellular damage, which may involve liver necrosis and liver failure; some cases have been fatal. Additionally, one case of Kawasaki-like syndrome with hepatic function changes was noted.

Immune System Disorders include anaphylactic reactions, angioedema, lupus-like syndrome, and systemic lupus erythematosus.

Nervous System Disorders have been characterized by reports of intracranial hypertension.

Renal and Urinary Disorders include acute renal failure, chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, and nephrotic syndrome.

Urine discoloration has been observed ex-vivo due to contact of mesalamine, including its inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Reproductive System and Breast Disorders have included reversible oligospermia.

Respiratory, Thoracic and Mediastinal Disorders reported include hypersensitivity pneumonitis (which encompasses interstitial pneumonitis, allergic alveolitis, and eosinophilic pneumonitis), interstitial lung disease, pleurisy/pleuritis, and pneumonitis.

Skin and Subcutaneous Tissue Disorders have included AGEP, DRESS, and SJS/TEN.

Patient Counseling

Advise patients to take the medication exactly as prescribed by their healthcare provider. It is important for patients to understand the dosage and frequency of administration to ensure optimal therapeutic outcomes.

Inform patients about the potential side effects associated with the medication. Patients should be made aware of common side effects, as well as any serious adverse reactions that may require immediate medical attention. Encourage patients to report any unusual symptoms or side effects they experience while taking the medication.

Discuss the importance of adhering to the prescribed treatment regimen. Emphasize that missing doses can affect the effectiveness of the therapy and may lead to complications. If a patient misses a dose, instruct them to take it as soon as they remember, unless it is close to the time of the next scheduled dose.

Instruct patients to avoid certain activities or substances that may interact with the medication. This may include alcohol, specific foods, or other medications. Provide guidance on what to avoid and the reasons for these precautions.

Encourage patients to maintain regular follow-up appointments to monitor their progress and any potential side effects. This will help ensure that the treatment remains effective and safe.

Finally, remind patients to keep the medication out of reach of children and to store it as directed, typically in a cool, dry place. Advise them to dispose of any unused medication properly, following local guidelines.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a controlled room temperature of 25°C (77°F). Temporary excursions are permissible within the range of 15°C to 30°C (59°F to 86°F), in accordance with USP guidelines for controlled room temperature. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Postmarketing experience has revealed a range of adverse events associated with the use of the medication. Cardiac disorders reported include chest pain, fatal myocarditis, pericarditis, and T-wave abnormalities. Hematologic disorders such as agranulocytosis, anemia, aplastic anemia, leukopenia, and pancytopenia have also been observed. Hepatic disorders include cirrhosis, jaundice (including cholestatic jaundice), hepatotoxicity, hepatitis, and possible hepatocellular damage, with some cases resulting in fatal outcomes. Notably, one case of Kawasaki-like syndrome with hepatic function changes was documented.

Additional adverse effects encompass immune system disorders like anaphylactic reactions, angioedema, lupus-like syndrome, and systemic lupus erythematosus. Nervous system disorders include intracranial hypertension, while renal and urinary disorders consist of acute and chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, and nephrotic syndrome. Clinicians should also be aware of urine discoloration occurring ex-vivo due to contact with hypochlorite-containing bleach. Reproductive system effects include reversible oligospermia. Respiratory disorders reported include hypersensitivity pneumonitis (with subtypes such as interstitial pneumonitis, allergic alveolitis, and eosinophilic pneumonitis), interstitial lung disease, pleurisy/pleuritis, and pneumonitis. Skin and subcutaneous tissue disorders include AGEP, DRESS, and SJS/TEN.

FDA Insert (PDF)

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

View full prescribing information (PDF)