Budesonide

Description

Budesonide rectal foam contains budesonide, a non-halogenated synthetic glucocorticoid, as the active ingredient. It is a mixture of the two epimers (22R and 22S), which differ in the position of an acetal chain, and both epimers are 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 g/mol. Each metered dose of budesonide 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

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 the first 2 weeks. Following this initial period, the dosage should be adjusted to 1 metered dose administered rectally once daily for the subsequent 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 a known hypersensitivity to budesonide or any of its components.

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, as well as those with untreated fungal, bacterial, systemic viral, or parasitic infections, or ocular herpes simplex, should be monitored closely.

Other Glucocorticosteroid Effects Patients with conditions where glucocorticoids may exert unwanted effects require careful observation.

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 combustion.

These warnings and precautions are critical for ensuring the safe use of budesonide rectal foam in clinical practice.

Side Effects

Patients receiving budesonide 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 budesonide, 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 transitioned from other glucocorticoids with high systemic effects, it is crucial to taper the dosage slowly. This approach helps to mitigate the risk of withdrawal symptoms and the unmasking of allergies, such as rhinitis and eczema. Additionally, patients with other conditions where glucocorticoids may have unwanted effects should be monitored closely.

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.

Hypersensitivity reactions to budesonide or any of its ingredients have been reported, and while acute overdosage with budesonide rectal foam 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 is available.

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. Children receiving corticosteroids through any route may experience a decrease in growth velocity, which has been noted even in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression. The long-term consequences of this reduction in growth velocity, 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 some commonly used tests of HPA axis function. Therefore, it is essential to monitor the linear growth of children treated with corticosteroids, utilizing methods such as stadiometry. The potential effects on growth associated with prolonged corticosteroid treatment should be carefully weighed against the clinical benefits achieved and the availability of alternative treatment options. To minimize the risk of growth suppression, children should 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, 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 presence of concomitant diseases or the use of 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 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 observed 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 (MRHD). These findings occurred in the presence of maternal toxicity.

Healthcare professionals should weigh the potential benefits and risks of budesonide use in pregnant patients and consider alternative therapies when appropriate.

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

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

Recommended Actions

In the event of suspected chronic overdosage, it is essential to assess the patient for any manifestations of hypercorticism, which may include symptoms such as weight gain, hypertension, and glucose intolerance.

Management Procedures

Management of chronic overdosage should focus on the gradual reduction of the budesonide dosage, along with close monitoring of the patient's clinical status. If significant symptoms of hypercorticism are observed, appropriate interventions should be initiated to mitigate these effects.

Healthcare professionals are advised to report any cases of overdosage to the relevant authorities and consider consulting a poison control center for further guidance.

Nonclinical Toxicology

No teratogenic effects were observed in nonclinical studies. In rats, budesonide did not affect fertility at subcutaneous doses up to 80 mcg/kg, which is approximately 0.20 times the recommended intrarectal dose of 4 mg/day in humans, based on body surface area. However, at subcutaneous doses of 20 mcg/kg (approximately 0.05 times the recommended intrarectal dose), there was a decrease in prenatal viability and viability in pups at birth and during lactation, along with a reduction in maternal body-weight gain. No adverse effects were noted at a dose of 5 mcg/kg.

Carcinogenicity studies conducted with budesonide in rats and mice revealed significant findings. 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 (approximately 0.12 times the recommended intrarectal dose). Additionally, there were increased incidences of primary hepatocellular tumors in male rats at doses of 25 mcg/kg and above. No tumorigenicity was noted 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 observed at the same oral dose of 50 mcg/kg; however, a statistically significant increase in hepatocellular tumors was noted. Concurrent studies with reference glucocorticosteroids, such as prednisolone and triamcinolone acetonide, demonstrated similar findings. In a 91-week study in mice, budesonide did not exhibit 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 various tests, including the Ames test, the mouse lymphoma cell forward gene mutation 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.

Postmarketing Experience

Budesonide rectal foam has been associated with several adverse events reported voluntarily or through surveillance programs. Notably, there is a potential for hypercorticism and adrenal suppression, particularly in patients transitioning from systemic corticosteroids, who should taper their dosage gradually. The replacement of systemic glucocorticosteroids with budesonide rectal foam may lead to the unmasking of previously controlled allergies, such as rhinitis and eczema.

Patients using budesonide rectal foam are at an increased risk for various infections, including exacerbation of existing tuberculosis, as well as fungal, bacterial, viral, or parasitic infections, and ocular herpes simplex. It is advised that patients contact their physician if they experience any symptoms indicative of infection.

Serious side effects associated with budesonide rectal foam include hypercorticism, adrenal suppression, immune system effects, and a heightened risk of infections. Chronic use may result in insufficient steroid hormone production by the adrenal glands. Additionally, patients may experience a resurgence of allergies if they switch from other corticosteroid medications.

Commonly reported side effects include decreased blood cortisol levels, adrenal insufficiency, and nausea. Patients are encouraged to report any side effects that are bothersome or persistent. Reports of side effects can be made 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 the medication. It is important to emphasize that budesonide rectal foam is intended for rectal application only and is not for oral use.

Before using budesonide 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. Budesonide rectal foam can be administered while standing, lying down, or sitting, such as during toilet use.

Patients should apply budesonide rectal 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 is recommended to do so immediately before bedtime, and patients should try 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 budesonide 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 budesonide rectal foam may lead to hypercorticism and adrenal suppression. If patients are transitioning from systemic corticosteroids to budesonide rectal foam, they should be advised to taper off the systemic corticosteroids slowly. Furthermore, patients should be made aware that replacing systemic glucocorticosteroids with budesonide 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 budesonide rectal foam may cause fetal harm and should notify their healthcare provider if they are pregnant or suspect they may be pregnant.

Storage and Handling

Budesonide rectal foam is supplied in a canister that contains a flammable propellant. 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). 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. Additionally, it is crucial to avoid fire, flame, or smoking during and immediately following administration. The canister is under pressure; therefore, it should not be punctured or incinerated.

Additional Clinical Information

Patients should be instructed to avoid fire, flame, and smoking during and immediately following the administration of budesonide rectal foam. Additionally, it is important for patients to temporarily discontinue the use of this medication prior to initiating bowel preparation for colonoscopy. They should consult their healthcare provider before resuming therapy after the procedure.

FDA Insert (PDF)

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

View full prescribing information (PDF)