Uceris

Description

UCERIS (budesonide) extended-release tablets are formulated for oral administration and contain budesonide, a synthetic corticosteroid, as the active ingredient. Budesonide is chemically designated as (RS)-11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde, existing as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C25H34O6, with a molecular weight of 430.5.

The structural formula of budesonide is represented as follows:

Budesonide appears as a white to off-white, odorless, crystalline powder that is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in chloroform. UCERIS is designed as a delayed and extended-release tablet, coated with a polymer film that disintegrates at or above pH 7. The tablet core comprises budesonide combined with polymers that facilitate the extended release of the active ingredient.

Each tablet contains the following inactive ingredients: stearic acid, lecithin, microcrystalline cellulose, hydroxypropyl cellulose, lactose, silicon dioxide, magnesium stearate, methacrylic acid copolymer types A and B, talc, triethyl citrate, and titanium dioxide.

Uses and Indications

UCERIS (budesonide) is indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis.

There are no teratogenic or nonteratogenic effects associated with UCERIS.

Dosage and Administration

The recommended dosage for the induction of remission in adult patients with active, mild to moderate ulcerative colitis is one 9 mg tablet taken once daily in the morning. This can be administered with or without food. The treatment duration should not exceed 8 weeks.

Contraindications

Use of UCERIS tablets is contraindicated in patients with a known hypersensitivity to budesonide or any of the ingredients contained in the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Hypercorticism and adrenal suppression may occur with treatment; therefore, healthcare professionals should closely monitor patients for signs and symptoms indicative of these conditions.

When transferring patients from systemic glucocorticoids to UCERIS, there is a risk of impaired adrenal function. It is essential to taper patients slowly from systemic corticosteroids to mitigate this risk.

Patients receiving treatment may experience immunosuppression, leading to an increased risk of various infections, including viral, bacterial, fungal, protozoal, and helminthic infections. Notably, there is a potential risk for severe infections such as varicella and measles. Healthcare providers should monitor patients for any new or worsening infections and consider discontinuation of the drug if such infections arise. The use of this medication is contraindicated in patients with active fungal infections, Strongyloides infestation, cerebral malaria, and ocular herpes simplex. Additionally, screening for hepatitis B infection is recommended prior to initiating treatment.

Kaposi’s sarcoma has been reported in patients undergoing corticosteroid therapy, particularly those being treated for chronic conditions.

To ensure patient safety, it is crucial to conduct laboratory tests to screen for hepatitis B infection before starting treatment. Regular monitoring for infections is advised, and healthcare professionals should be prepared to discontinue the medication if any new or worsening infections are detected.

Side Effects

Most common adverse reactions observed in patients include headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, and constipation.

Serious side effects associated with treatment include hypercorticism and adrenal suppression, which may occur and necessitate monitoring for signs and symptoms. Patients may also experience immunosuppression, leading to an increased risk of infections, including viral, bacterial, fungal, protozoal, and helminthic infections. This includes potentially fatal infections such as varicella and measles. It is essential to monitor patients for new or worsening infections and consider discontinuation of the drug if necessary. The use of this medication is contraindicated in patients with fungal infections, Strongyloides infestation, cerebral malaria, and ocular herpes simplex, and screening for hepatitis B infection is recommended. Additionally, Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly for chronic conditions.

Patients with known hypersensitivity to budesonide or any of the ingredients in UCERIS tablets should not use this medication. There is a risk of impaired adrenal function when transitioning from glucocorticoid treatments with higher systemic effects to those with lower systemic effects, such as UCERIS; therefore, a gradual tapering of systemic corticosteroids is advised.

The safety and effectiveness of UCERIS in pediatric patients have not been established, and glucocorticosteroids may lead to a reduction in growth velocity in this population. Clinical studies did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. However, other clinical experiences have not identified significant differences in responses between elderly and younger patients. Caution is advised when using UCERIS in elderly patients due to the potential for decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

Infants born to mothers who received corticosteroids during pregnancy may experience hypoadrenalism. These infants should be closely monitored for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Drug Interactions

The concomitant use of cytochrome P450 3A4 inhibitors, such as ketoconazole and grapefruit juice, is contraindicated due to the potential for increased systemic corticosteroid effects. This interaction may lead to an enhanced risk of corticosteroid-related adverse effects.

It is advisable to monitor patients closely for signs of increased corticosteroid activity and to consider dosage adjustments of corticosteroids if these inhibitors are used concurrently.

Packaging & NDC

The table below lists all NDC Code configurations of Uceris (budesonide), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of UCERIS in pediatric patients have not been established. Caution is advised when considering the use of glucocorticosteroids, including UCERIS, in this population, as they may cause a reduction in growth velocity in pediatric patients.

Geriatric Use

Clinical studies of UCERIS did not include a sufficient number of subjects aged 65 and older to determine whether these elderly patients respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly and younger patients.

In general, UCERIS should be used cautiously in geriatric patients. This caution is warranted due to the potential for decreased hepatic, renal, or cardiac function in this population, as well as the possibility of concomitant diseases or other drug therapies that may complicate treatment. Healthcare providers are advised to monitor elderly patients closely for any adverse effects and to consider potential dose adjustments based on individual patient factors.

Pregnancy

Limited published studies report on the use of budesonide in pregnant women; however, the data are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Animal reproduction studies have demonstrated that subcutaneous administration of budesonide during organogenesis in pregnant rats and rabbits at doses of 0.5 times and 0.05 times, respectively, the maximum recommended human dose resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities. Maternal toxicity was also observed in both species at these dose levels.

Based on the available animal data, healthcare professionals should advise pregnant women of the potential risks to the fetus associated with budesonide use. The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2% to 4% and 15% to 20%, respectively. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes.

In women with ulcerative colitis, increased disease activity has been associated with adverse pregnancy outcomes, including preterm delivery, low birth weight infants, and small for gestational age at birth. Additionally, hypoadrenalism may occur in infants born to mothers receiving corticosteroids during pregnancy. Infants should be carefully monitored for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Budesonide has been shown to be teratogenic and embryolethal in animal studies. In an embryofetal development study involving pregnant rats, subcutaneous doses of budesonide during the period of organogenesis (gestation days 6-15) resulted in effects on fetal development and survival at doses up to approximately 500 mcg/kg. Similarly, in pregnant rabbits, dosing during organogenesis (gestation days 6-18) led to increased maternal abortion rates and adverse effects on fetal development at doses up to approximately 25 mcg/kg. Maternal toxicity, including reduced body weight gain, was noted at lower doses in both species.

In a peri- and postnatal development study, rats dosed with budesonide from Day 15 post coitum to Day 21 postpartum showed no effects on delivery; however, there were significant impacts on the growth and development of offspring, including reduced survival and decreased mean body weights at birth and during lactation at exposures of 0.02 times the maximum recommended human dose. These findings occurred in the context of maternal toxicity.

Lactation

Lactating mothers who have received corticosteroids during pregnancy should be aware of the potential risk of hypoadrenalism in their breastfed infants. It is important for healthcare professionals to monitor these infants closely for signs of hypoadrenalism, which may include poor feeding, irritability, weakness, and vomiting. If any of these symptoms are observed, appropriate management should be initiated.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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 available information.

Overdosage

Acute toxicity and fatalities associated with glucocorticosteroid overdosage are infrequently reported. In the event of an overdose, immediate intervention is critical. Recommended treatment includes gastric lavage or the induction of emesis, followed by supportive and symptomatic care to manage any arising complications.

Prolonged use of glucocorticosteroids at excessive doses may lead to systemic effects, including hypercorticism and adrenal suppression. In cases of chronic overdosage, particularly when necessitated by severe underlying conditions requiring ongoing steroid therapy, a temporary reduction in dosage may be warranted to mitigate adverse effects.

Experimental data indicate that single oral doses of budesonide at 200 mg/kg and 400 mg/kg were lethal in female and male mice, respectively. Observed signs of acute toxicity in these studies included decreased motor activity, piloerection, and generalized edema. These findings underscore the importance of adhering to recommended dosing guidelines to prevent serious health consequences.

Nonclinical Toxicology

Carcinogenicity studies with budesonide were conducted in rats and mice. In a two-year study involving Sprague-Dawley rats, a statistically significant increase in the incidence of gliomas was observed in male rats at an oral dose of 50 mcg/kg, which is approximately 0.05 times the maximum recommended human dose on a body surface area basis. Additionally, there were increased incidences of primary hepatocellular tumors in male rats at doses of 25 mcg/kg and above, with no tumorigenicity noted in female rats at oral doses up to 50 mcg/kg. In a separate two-year study in male Sprague-Dawley rats, no gliomas were observed at the same oral dose of 50 mcg/kg; however, a statistically significant increase in hepatocellular tumors was noted at this dose. Concurrent reference glucocorticosteroids, such as prednisolone and triamcinolone acetonide, exhibited similar findings. In a 91-week study in mice, budesonide did not demonstrate treatment-related carcinogenicity at oral doses up to 200 mcg/kg, approximately 0.1 times the maximum recommended human dose on a body surface area basis.

Budesonide was not found to be genotoxic in several assays, including the Ames test, the mouse lymphoma cell forward gene mutation (TK +/-) test, the human lymphocyte chromosome aberration test, the Drosophila melanogaster sex-linked recessive lethality test, the rat hepatocyte unscheduled DNA synthesis (UDS) test, and the mouse micronucleus test.

In terms of fertility, budesonide did not affect fertility in rats at subcutaneous doses up to 80 mcg/kg, approximately 0.07 times the maximum recommended human dose on a body surface area basis. However, a decrease in prenatal viability and viability in pups at birth and during lactation was observed, along with a reduction in maternal body weight gain, at subcutaneous doses of 20 mcg/kg and above. No such effects were noted at a dose of 5 mcg/kg, approximately 0.005 times the maximum recommended human dose on a body surface area basis.

Postmarketing Experience

Kaposi’s sarcoma has been reported in patients receiving corticosteroids for chronic conditions. It is advised that patients inform their healthcare provider if they experience any signs or symptoms indicative of Kaposi’s sarcoma.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) to understand the important information regarding their treatment. Those treated with UCERIS extended-release tablets should receive specific information and instructions to ensure the safe and effective use of the medication.

It is important to inform patients that UCERIS extended-release tablets may lead to systemic glucocorticosteroid effects, including hypercorticism and adrenal suppression. Patients should be counseled to taper slowly from systemic corticosteroids if they are transitioning to UCERIS extended-release tablets.

Patients should also be advised to avoid exposure to individuals with varicella (chicken pox) or measles. They must inform their healthcare provider if they have been exposed to varicella or measles, or if they develop a new or worsening infection.

Additionally, patients should be made aware that Kaposi’s sarcoma has been reported in individuals receiving corticosteroids for chronic conditions. They should notify their healthcare provider if they experience any signs or symptoms indicative of Kaposi’s sarcoma.

Patients must be instructed to swallow UCERIS extended-release tablets whole with water and to avoid chewing or crushing the tablets. Furthermore, they should refrain from consuming grapefruit juice during the entire course of UCERIS therapy.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to maintain its integrity. It should be stored at a temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines. Additionally, it is essential to protect the product from light and moisture to ensure optimal stability and efficacy.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)