Uceris

Description

UCERIS rectal foam contains budesonide, a non-halogenated synthetic glucocorticoid, as the active ingredient. It is composed of a mixture of the two epimers (22R and 22S), which differ in the position of an acetal chain, with both epimers being active glucocorticoids present in approximately equal proportions. Budesonide is chemically designated as (RS)-11β, 16α, 17,21 tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. The empirical formula of budesonide is C25H34O6, and its molecular weight is 430.5. Each metered dose of UCERIS rectal foam delivers 2 mg of budesonide. Inactive ingredients include cetyl alcohol, citric acid monohydrate, edetate disodium, emulsifying wax, polyoxyl (10) stearyl ether, propylene glycol, and purified water. The propellant used in the formulation consists of n-butane, isobutane, and propane.

Uses and Indications

UCERIS rectal foam is indicated for the induction of remission in patients with active mild to moderate distal ulcerative colitis extending up to 40 cm from the anal verge.

There are no teratogenic or nonteratogenic effects associated with the use of UCERIS rectal foam.

Dosage and Administration

The recommended dosage for the medication is 1 metered dose administered rectally twice daily for a duration of 2 weeks. Following this initial treatment period, the dosage should be adjusted to 1 metered dose administered rectally once daily for an additional 4 weeks.

Prior to administration, it is essential to warm the canister in the hands while shaking it vigorously for 10 to 15 seconds to ensure proper preparation of the medication.

Contraindications

Use of UCERIS rectal foam is contraindicated in patients with known hypersensitivity to budesonide or any of the ingredients contained in the formulation.

Warnings and Precautions

Patients receiving treatment with UCERIS rectal foam should be closely monitored for several critical warnings and precautions associated with glucocorticosteroid therapy.

Hypercorticism and Adrenal Suppression Healthcare professionals should adhere to established guidelines regarding the use of glucocorticosteroids, as patients may experience hypercorticism and adrenal suppression.

Impaired Adrenal Function in Patients Transferred from Other Glucocorticoids When transitioning patients from other glucocorticosteroids with significant systemic effects, it is essential to taper the dosage gradually. Clinicians must monitor for withdrawal symptoms and be vigilant for the unmasking of allergies, such as rhinitis and eczema.

Increased Risk of Infection There is an elevated risk of infections, including serious and potentially fatal conditions such as chickenpox and measles. It is crucial to monitor patients who have a history of active or quiescent tuberculosis, as well as those with untreated fungal, bacterial, systemic viral, or parasitic infections, and ocular herpes simplex.

Other Glucocorticosteroid Effects Patients with pre-existing conditions that may be exacerbated by glucocorticoids should be monitored closely for any unwanted effects.

Flammable Contents The contents of UCERIS rectal foam are flammable. Patients should be instructed to avoid exposure to fire, flames, and smoking during and immediately after administration to prevent any fire hazards.

In summary, careful monitoring and adherence to these warnings and precautions are essential for the safe use of UCERIS rectal foam in patients undergoing glucocorticosteroid therapy.

Side Effects

Patients receiving UCERIS rectal foam may experience a range of adverse reactions. The most common adverse reactions reported include decreased blood cortisol, adrenal insufficiency, and nausea.

Serious adverse reactions associated with the use of glucocorticosteroids, including UCERIS, necessitate careful monitoring. Patients are at an increased risk of infections, which may include serious and potentially fatal cases of chicken pox and measles. It is essential to monitor patients with active or quiescent tuberculosis infections, as well as those with untreated fungal, bacterial, systemic viral, or parasitic infections, and ocular herpes simplex.

In patients who are being transferred from other glucocorticoids, there is a risk of impaired adrenal function. It is recommended to taper slowly from glucocorticoids that have high systemic effects and to monitor for withdrawal symptoms and the unmasking of allergies, such as rhinitis and eczema.

Additional considerations include the potential for hypercorticism and adrenal suppression, which align with general warnings concerning glucocorticosteroids. Patients with other conditions where glucocorticoids may have unwanted effects should also be monitored closely.

It is important to note that the contents of UCERIS rectal foam are flammable. Patients should be instructed to avoid fire, flame, and smoking during and immediately following administration.

Hypersensitivity reactions to budesonide or any of the ingredients in UCERIS rectal foam have been reported. While acute overdosage is unlikely, chronic overdosage may lead to signs and symptoms of hypercorticism.

Drug Interactions

CYP3A4 inhibitors, such as ketoconazole and grapefruit juice, may lead to increased systemic effects of corticosteroids. It is advisable to avoid concomitant use of these agents to prevent potential adverse effects associated with elevated corticosteroid levels.

No information regarding drug and laboratory test interactions has been provided.

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

The safety and effectiveness of UCERIS rectal foam have not been established in pediatric patients. Corticosteroid treatment in children, regardless of the route of administration, may lead to a decrease in growth velocity. This reduction in growth velocity has been observed even in the absence of laboratory evidence indicating hypothalamic-pituitary-adrenal (HPA) axis suppression. The long-term consequences of this decrease, including its potential impact on final adult height, remain unknown.

Growth velocity may serve as a more sensitive indicator of systemic corticosteroid exposure in children compared to commonly used tests of HPA axis function. Therefore, it is essential to monitor the linear growth of children receiving corticosteroids, utilizing methods such as stadiometry. The potential effects on growth associated with prolonged corticosteroid treatment should be carefully considered against the clinical benefits achieved and the availability of alternative treatment options. To mitigate the risk of growth suppression, it is recommended that children be titrated to the lowest effective dose of corticosteroids.

Geriatric Use

Clinical studies involving UCERIS rectal foam did not include a sufficient number of patients aged 65 and older to ascertain whether this population responds differently compared to younger patients. However, other reported clinical experiences have not identified any significant differences in responses between elderly patients and their younger counterparts.

In general, when prescribing for geriatric patients, dose selection should be approached with caution. It is advisable to initiate treatment at the lower end of the dosing range. This recommendation is particularly important due to the increased likelihood of diminished hepatic, renal, or cardiac function in elderly patients, as well as the potential for concomitant diseases or interactions with other drug therapies. Careful monitoring and consideration of these factors are essential to ensure the safety and efficacy of treatment in this population.

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. In animal reproduction studies, subcutaneous administration of budesonide during organogenesis in pregnant rats and rabbits resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities at doses 1.2 times and 0.12 times, respectively, the human intrarectal dose of 4 mg/day. Maternal toxicity was also observed in both species at these dose levels.

Based on animal data, healthcare professionals should advise pregnant women of the potential risks to a fetus. 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. Additionally, published data suggest that increased disease activity in women with ulcerative colitis is associated with adverse pregnancy outcomes, including preterm delivery, low birth weight infants, and small for gestational age at birth.

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 embryo-fetal development study in pregnant rats, effects on fetal development and survival were observed at subcutaneous doses up to approximately 500 mcg/kg, while in pregnant rabbits, there was an increase in maternal abortion and effects on fetal development at doses up to approximately 25 mcg/kg.

In a pre-and post-natal development study, rats dosed with budesonide during the period from Day 15 post coitum to Day 21 postpartum showed no effects on delivery; however, there were adverse effects on the growth and development of offspring, including reduced survival and decreased mean body weights at birth and during lactation at exposures of 0.05 times the maximum recommended human dose. These findings occurred in the presence of maternal toxicity.

Lactation

Lactation studies have not been conducted with UCERIS rectal foam or other rectally administered budesonide products, and no information is available on the effects of budesonide on the breastfed infant or on milk production. However, one published study indicates that budesonide is present in human milk following maternal inhalation, with a milk/plasma ratio ranging between 0.4 and 0.5.

Budesonide plasma concentrations were not detected, and no adverse events were noted in breastfed infants following maternal use of inhaled budesonide. It is important to consider the developmental and health benefits of breastfeeding alongside the mother’s clinical need for UCERIS rectal foam and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Given that budesonide exposure to the nursing child may be higher with maternal rectal administration of UCERIS compared to inhaled administration, healthcare professionals should weigh these factors when advising lactating mothers. The estimated budesonide AUC following rectal administration of 2 mg twice a day UCERIS was 4.31 ng*hr/mL.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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 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 available information.

Overdosage

Acute overdosage with UCERIS rectal foam is considered unlikely. However, in cases of chronic overdosage, healthcare professionals should be vigilant for potential signs and symptoms of hypercorticism.

Management of Overdosage

In the event of suspected chronic overdosage, it is recommended that healthcare providers assess the patient for symptoms associated with hypercorticism, which may include but are not limited to weight gain, hypertension, diabetes, and changes in mood or behavior.

Appropriate management should involve discontinuation of UCERIS rectal foam and supportive care tailored to the patient's clinical presentation. Monitoring and evaluation of the patient's condition are essential to mitigate any adverse effects associated with prolonged exposure to elevated corticosteroid levels.

Nonclinical Toxicology

Carcinogenicity studies with budesonide were conducted in rats and mice. In a 2-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 0.12 times the recommended intrarectal dose of 4 mg/day in humans, based on body surface area. Additionally, increased incidences of primary hepatocellular tumors were noted in male rats at doses of 25 mcg/kg and above, which corresponds to approximately 0.06 times the recommended intrarectal dose. No tumorigenicity was observed in female rats at oral doses up to 50 mcg/kg. In a separate 2-year study in male Sprague-Dawley rats, no gliomas were detected at the same oral dose of 50 mcg/kg; however, a statistically significant increase in hepatocellular tumors was again noted at this dose. The concurrent reference glucocorticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings. In a 91-week study in mice, budesonide did not demonstrate any treatment-related carcinogenicity at oral doses up to 200 mcg/kg, approximately 0.24 times the recommended intrarectal dose.

Budesonide showed no evidence of mutagenic potential in several tests, 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 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 0.20 times the recommended intrarectal dose. 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, which is approximately 0.05 times the recommended intrarectal dose. No such effects were noted at a dose of 5 mcg/kg.

Postmarketing Experience

Postmarketing experience with UCERIS rectal foam has identified several important considerations for patients and healthcare providers. Reports indicate that the use of UCERIS rectal foam may lead to hypercorticism and adrenal suppression. It is recommended that patients taper slowly from systemic corticosteroids when transitioning to UCERIS rectal foam.

Additionally, the replacement of systemic glucocorticosteroids with UCERIS rectal foam may unmask previously controlled allergies, such as rhinitis and eczema. Patients are advised to be vigilant for the resurgence of these conditions and to inform their healthcare provider if any allergies worsen during treatment.

There is an increased risk of developing various infections, including exacerbation of existing tuberculosis, as well as fungal, bacterial, viral, or parasitic infections, and ocular herpes simplex. Patients should seek medical attention if they experience any symptoms indicative of infection. Furthermore, UCERIS rectal foam may compromise the immune system, heightening susceptibility to infections. Patients are encouraged to avoid close contact with individuals who have contagious diseases, such as chicken pox or measles, while using this medication.

Common side effects reported include decreased blood cortisol levels, adrenal insufficiency, and nausea. Patients are urged to report any side effects that are bothersome or persistent to their healthcare provider. Adverse events can also be reported to the FDA at 1-800-FDA-1088.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the PATIENT INFORMATION and INSTRUCTIONS FOR USE, to ensure proper understanding of UCERIS rectal foam. It is important to emphasize that UCERIS rectal foam is intended for rectal application only and is not for oral use.

Before using UCERIS rectal foam, patients should be instructed to empty their bowels. Each applicator is pre-coated with a lubricant; however, if additional lubrication is necessary, petrolatum or petroleum jelly may be used. Patients should warm the canister in their hands and shake it vigorously for 10 to 15 seconds prior to use. UCERIS rectal foam can be administered while standing, lying down, or sitting, such as during toilet use.

Patients should apply UCERIS rectal foam in the morning and evening for the first two weeks of treatment, followed by once daily in the evening for the subsequent four weeks. When applying in the evening, it is recommended that patients do so immediately before bedtime and to avoid emptying their bowels again until the following morning.

Healthcare providers should caution patients to avoid consuming grapefruit or grapefruit juice during treatment with UCERIS rectal foam. Additionally, patients should be informed about the flammability of the foam and advised to avoid fire, flame, and smoking during and immediately after administration.

It is essential to inform patients that UCERIS rectal foam may lead to hypercorticism and adrenal suppression. If patients are transitioning from systemic corticosteroids to UCERIS rectal foam, they should be advised to taper their systemic corticosteroids slowly. Furthermore, patients should be made aware that replacing systemic glucocorticosteroids with UCERIS rectal foam may unmask previously controlled allergies, such as rhinitis and eczema.

Patients should also be advised to avoid exposure to individuals with chickenpox or measles, and to consult their physician if they have been exposed. They should be informed of the increased risk of developing various infections, including exacerbation of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Patients should contact their physician if they experience any symptoms of infection.

Finally, female patients should be informed that UCERIS rectal foam may cause fetal harm and should notify their healthcare provider if they are known to be pregnant or suspect they may be pregnant.

Storage and Handling

UCERIS rectal foam is supplied in a pressurized canister. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) as defined by USP Controlled Room Temperature guidelines.

The product must not be exposed to heat or stored at temperatures exceeding 120°F (49°C). Refrigeration is strictly prohibited. Due to the presence of a flammable propellant, it is critical to avoid any exposure to fire, flame, or smoking during and immediately after administration. Additionally, the canister should not be burned after use, and the contents must not be sprayed directly towards flames.

The canister is under pressure; therefore, it should not be punctured or incinerated.

Additional Clinical Information

The contents of UCERIS rectal foam include n-butane, isobutane, and propane as propellants, which are flammable. Clinicians should instruct patients to avoid fire, flame, and smoking during and immediately following administration.

Patients are advised to temporarily discontinue the use of UCERIS rectal foam prior to bowel preparation for colonoscopy and should consult their healthcare provider before resuming therapy.

FDA Insert (PDF)

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

View full prescribing information (PDF)