Budesonide

Description

Budesonide rectal foam is a formulation containing budesonide, a non-halogenated synthetic glucocorticoid, as the active ingredient. This product consists of a mixture of the two epimers, 22R and 22S, which differ in the position of an acetal chain, with both epimers exhibiting glucocorticoid activity in an approximate 1:1 ratio.

Chemically, budesonide is designated as (RS)-11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde, with an empirical formula of C25H34O6 and a molecular weight of 430.5. Each metered dose of the rectal foam delivers 2 mg of budesonide.

The formulation includes several inactive ingredients: cetyl alcohol, citric acid monohydrate, edetate disodium, emulsifying wax, polyoxyl (10) stearyl ether, propylene glycol, and purified water. The propellant used in the foam consists of n-butane, isobutane, and propane.

Uses and Indications

Budesonide 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 this medication.

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 budesonide rectal foam is contraindicated in patients with known hypersensitivity to budesonide or any of its components. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Patients receiving budesonide rectal foam should be closely monitored for several critical warnings and precautions associated with its use.

Hypercorticism and Adrenal Suppression Healthcare professionals should adhere to general warnings regarding glucocorticosteroids, as patients may experience hypercorticism and adrenal suppression.

Impaired Adrenal Function in Patients Transferred from Other Glucocorticoids When transitioning patients from other glucocorticoids with high systemic effects, it is essential to taper the dosage slowly. 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 cases of chickenpox and measles. Patients with active or quiescent tuberculosis infections, untreated fungal, bacterial, systemic viral, or parasitic infections, or ocular herpes simplex should be monitored closely.

Other Glucocorticosteroid Effects Patients with conditions that may be adversely affected by glucocorticoids should also be monitored for unwanted effects.

Flammable Contents The contents of budesonide rectal foam are flammable. Patients should be instructed to avoid fire, flames, and smoking during and immediately following administration to prevent any risk of fire-related incidents.

Healthcare professionals are encouraged to maintain a high index of suspicion for these warnings and to implement appropriate monitoring strategies to ensure patient safety.

Side Effects

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

Serious adverse reactions associated with the use of glucocorticosteroids, including budesonide, necessitate careful monitoring. There is an increased risk of infection, which may include serious and potentially fatal cases of chicken pox and measles. Patients with active or quiescent tuberculosis infections, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex should be closely monitored.

Patients transitioning from other glucocorticosteroids with high systemic effects may experience impaired adrenal function. It is recommended to taper these medications slowly while monitoring for withdrawal symptoms and the unmasking of allergies, such as rhinitis and eczema.

Additional considerations include the potential for hypoadrenalism in infants born to mothers who received corticosteroids during pregnancy. These infants should be observed for signs of hypoadrenalism, including poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Patients should also be informed that the contents of budesonide rectal foam are flammable, and they should avoid fire, flame, and smoking during and immediately following administration. Known hypersensitivity to budesonide or any of its ingredients is a contraindication for use. While acute overdosage with budesonide rectal foam is unlikely, chronic overdosage may lead to signs and symptoms of hypercorticism. Furthermore, it is important to note that budesonide has been shown to be teratogenic and embryolethal in animal studies involving rabbits and rats.

Overall, healthcare providers should monitor patients for these adverse reactions and manage them appropriately to ensure patient safety.

Drug Interactions

Concomitant use of CYP3A4 inhibitors, such as ketoconazole and grapefruit juice, may lead to increased systemic effects of corticosteroids. It is advisable to avoid the simultaneous administration of these agents to mitigate the risk of enhanced corticosteroid effects. Monitoring for signs of corticosteroid overactivity is recommended if such combinations cannot be avoided.

Packaging & NDC

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

Pediatric Use

The safety and effectiveness of budesonide 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.

Monitoring of linear growth in children receiving corticosteroids should be conducted, utilizing methods such as stadiometry, as growth velocity may serve as a more sensitive indicator of systemic corticosteroid exposure than some commonly used tests of HPA axis function. The potential effects on growth associated with prolonged corticosteroid treatment should be carefully considered in relation to 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 budesonide 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, dose selection for geriatric patients should be approached with caution. It is advisable to initiate treatment at the lower end of the dosing range, taking into account the increased likelihood of diminished hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Careful monitoring of these patients is recommended to ensure safety and efficacy.

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. Maternal toxicity was observed at doses 1.2 times and 0.12 times the human intrarectal dose of 4 mg/day, respectively.

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, and small for gestational age infants.

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, doses up to approximately 500 mcg/kg resulted in effects on fetal development and survival. Similarly, in pregnant rabbits, doses up to approximately 25 mcg/kg led to increased maternal abortion and effects on fetal development, as well as reduced litter weights. Maternal toxicity was noted at lower doses, indicating potential risks associated with budesonide use during pregnancy.

In a pre-and post-natal development study, budesonide did not affect delivery but impacted the growth and development of offspring, with reduced survival and decreased mean body weights observed at exposures of 0.05 times the maximum recommended human dose. These findings occurred alongside maternal toxicity, further emphasizing the need for caution when considering budesonide in pregnant patients.

Lactation

Lactation studies have not been conducted with budesonide 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. The systemic exposure (AUC0-12) following administration of 400 mcg twice a day of inhaled budesonide ranged from 1.27 to 2.26 nghr/mL. In contrast, the estimated budesonide AUC0-12 following rectal administration of 2 mg twice a day was 4.31 nghr/mL, suggesting that exposure to the nursing child may be higher with maternal rectal administration than with inhaled administration.

The developmental and health benefits of breastfeeding should be considered alongside the mother’s clinical need for budesonide rectal foam and any potential adverse effects on the breastfed child from the medication or from the underlying maternal condition.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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 overdosage with budesonide rectal foam is considered unlikely due to its pharmacokinetic properties. However, it is important to note that budesonide is absorbed systemically, and chronic overdosage may lead to significant clinical manifestations.

Potential Symptoms

In cases of chronic overdosage, patients may exhibit signs and symptoms consistent with hypercorticism. These may include, but are not limited to, weight gain, hypertension, glucose intolerance, and other features associated with excess corticosteroid exposure.

Recommended Actions

In the event of suspected chronic overdosage, healthcare professionals should monitor the patient closely for the development of hypercorticism symptoms. Management may involve the gradual tapering of budesonide therapy to mitigate potential adverse effects. Supportive care and symptomatic treatment should be provided as necessary, tailored to the individual patient's needs.

It is essential for healthcare providers to remain vigilant and to educate patients regarding the importance of adhering to prescribed dosages to minimize the risk of overdosage and its associated complications.

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. 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. Concurrent reference glucocorticosteroids, such as 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 of 4 mg/day in humans.

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 of 4 mg/day in humans. 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.

Postmarketing Experience

Postmarketing experience has indicated that budesonide rectal foam may be associated with hypercorticism and adrenal suppression. Additionally, the replacement of systemic glucocorticosteroids with budesonide rectal foam has been observed to potentially unmask previously controlled allergies, such as rhinitis and eczema. Furthermore, patients using this medication may be at an increased risk for a range of infections, including exacerbation of existing tuberculosis, as well as fungal, bacterial, viral, or parasitic infections, and ocular herpes simplex. Patients are advised to contact their physician if they experience any symptoms indicative of infection.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use, to ensure they understand the proper use of budesonide rectal foam. It is important to inform patients that budesonide rectal foam may lead to hypercorticism and adrenal suppression. Therefore, if they are transitioning from systemic corticosteroids to budesonide rectal foam, they should taper off the systemic corticosteroids slowly.

Patients should be made aware that replacing systemic glucocorticosteroids with budesonide rectal foam may unmask previously controlled allergies, such as rhinitis and eczema. They should also be cautioned against exposing the product to heat or storing it at temperatures exceeding 120°F (49°C), as it is flammable. Patients must avoid fire, flame, or smoking during and immediately after administration. Additionally, they should be informed that the contents are under pressure and that the canister should not be punctured or incinerated.

It is crucial to emphasize that budesonide rectal foam is intended for rectal use only and is not for oral consumption. Before using the foam, patients should empty their bowels. Each applicator is pre-coated with a lubricant, but if additional lubrication is necessary, petrolatum or petroleum jelly may be used. Patients should warm the canister in their hands while shaking it vigorously for 10 to 15 seconds prior to use.

Patients can apply budesonide rectal foam while standing, lying down, or sitting (e.g., while using the toilet). The recommended dosing schedule is to apply the foam in the morning and evening for the first two weeks of treatment, followed by once daily in the evening for the next four weeks. When applying in the evening, it should be done immediately before bedtime, and patients should try to avoid emptying their bowels again until the next morning.

Patients should also be advised to avoid consuming grapefruit or grapefruit juice during treatment with budesonide rectal foam. Furthermore, they should be informed about the increased risk of developing various infections, including the worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. If patients develop any symptoms of infection, they should contact their physician promptly. Additionally, they should avoid exposure to individuals with chickenpox or measles and consult a physician if such exposure occurs.

Storage and Handling

Budesonide 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, the canister should not be burned after use, and the contents must not be sprayed directly towards flames.

As the product is flammable, it is crucial to avoid fire, flame, or smoking during and immediately following administration. Additionally, the canister is under pressure; therefore, it should not be punctured or incinerated.

Additional Clinical Information

Budesonide rectal foam is administered exclusively via the rectal route and is not intended for oral use. For the initial two weeks of treatment, patients should apply the foam twice daily, in the morning and evening, followed by once daily in the evening for the subsequent four weeks. It is recommended that the evening application occurs immediately before bedtime, with a suggestion to avoid bowel movements until the following morning.

Prior to administration, patients are advised to empty their bowels. Each applicator is pre-lubricated, but additional lubrication with petrolatum or petroleum jelly may be used if necessary. The canister should be warmed in the hands and shaken vigorously for 10 to 15 seconds before use. Patients can assume a standing, lying, or sitting position during application. Clinicians should counsel patients to avoid concomitant use of CYP3A4 inhibitors, such as ketoconazole and grapefruit juice, and to refrain from fire, flame, and smoking during and immediately after administration. Additionally, patients should temporarily discontinue the use of budesonide rectal foam prior to bowel preparation for colonoscopy and consult their healthcare provider before resuming treatment.

FDA Insert (PDF)

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

View full prescribing information (PDF)