Budesonide

Description

Budesonide USP, the active ingredient in budesonide delayed-release capsules, is a synthetic corticosteroid. It is chemically designated as (RS)-11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde and exists as a mixture of two epimers (22R and 22S). The molecular formula of budesonide is C25H34O6, with a molecular weight of 430.5 g/mol.

Budesonide appears as a white to off-white crystalline powder that is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in methylene chloride. Its partition coefficient between octanol and water at pH 5 is 1.6 x 10^3 at an ionic strength of 0.01. Each delayed-release capsule for oral administration contains 3 mg of micronized budesonide, USP, along with inactive ingredients including cetyl alcohol, corn starch, ethyl cellulose, hypromellose, macrogol, methacrylic acid copolymer type C, sodium lauryl sulfate, sugar, talc, and triethyl citrate. The capsule shells consist of D&C yellow #10, FD&C blue #1, FD&C red #40, FD&C yellow #6, gelatin, and titanium dioxide. The monogramming ink contains D&C yellow #10, ethanol, FD&C blue #1, FD&C blue #2, FD&C red #40, iron oxide black, methanol, N-butyl alcohol, propylene glycol, and shellac.

Uses and Indications

Budesonide delayed-release capsules are indicated for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon in patients aged 8 years and older. Additionally, this drug is indicated for the maintenance of clinical remission of mild to moderate Crohn’s disease involving the ileum and/or the ascending colon for up to 3 months in adults.

There are no teratogenic or nonteratogenic effects associated with the use of budesonide delayed-release capsules.

Dosage and Administration

Patients should take the medication once daily in the morning. The capsules must be swallowed whole; they should not be chewed or crushed. For patients who are unable to swallow an intact capsule, the capsules may be opened, and the granules can be emptied onto one tablespoonful of applesauce. The mixture should be thoroughly mixed and consumed within 30 minutes without chewing or crushing the granules. Following this, the patient should drink 8 ounces of water. It is important to avoid the consumption of grapefruit juice during the entire course of therapy.

For the treatment of mild to moderate active Crohn’s disease, the recommended dosage is as follows:

• Adults: 9 mg once daily for up to 8 weeks. If necessary, repeat the 8-week treatment course for recurring episodes of active disease.

• Pediatrics (ages 8 to 17 years) weighing more than 25 kg: 9 mg once daily for up to 8 weeks, followed by a reduced dosage of 6 mg once daily in the morning for an additional 2 weeks.

For the maintenance of clinical remission of mild to moderate Crohn’s disease, the recommended dosage is:

• Adults: 6 mg once daily for up to 3 months, with a taper to complete cessation after this period. Continued treatment beyond 3 months has not demonstrated substantial clinical benefit.

• When transitioning from oral prednisolone, it is advised to begin tapering prednisolone concurrently with the initiation of budesonide delayed-release capsules.

In patients with moderate hepatic impairment (Child-Pugh Class B), consideration should be given to reducing the dosage to 3 mg once daily.

Contraindications

Use of budesonide delayed-release capsules is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients contained in the formulation.

Warnings and Precautions

Hypercorticism and adrenal axis suppression may occur with treatment. Healthcare professionals should closely monitor patients for signs and symptoms of these conditions, particularly in pediatric populations and individuals with hepatic impairment, who may be at an increased risk.

When transitioning patients from other systemic corticosteroids, it is essential to taper the dosage slowly, especially for those on corticosteroids with high systemic effects. Monitoring for withdrawal symptoms is crucial, as well as being vigilant for the unmasking of allergies, such as rhinitis and eczema.

Patients receiving corticosteroid therapy are at an increased risk of immunosuppression, which can lead to a heightened susceptibility to various infections, including viral, bacterial, fungal, protozoal, and helminthic infections. This risk encompasses potentially fatal infections such as varicella and measles. Healthcare providers should monitor patients for any new or worsening infections and consider discontinuation of the drug if necessary. The use of corticosteroids 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 therapy.

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

Furthermore, healthcare professionals should monitor patients with concomitant conditions that may exacerbate the unwanted effects of corticosteroids, such as hypertension and diabetes mellitus, to ensure safe and effective management of their overall health.

Side Effects

Most common adverse reactions occurring in patients treated with this medication include headache, respiratory infection, nausea, back pain, dyspepsia, dizziness, abdominal pain, flatulence, vomiting, fatigue, and pain, each reported in 5% or more of participants.

Serious adverse reactions may include hypercorticism and adrenal axis suppression, which can occur with treatment. Patients, particularly pediatrics and those with hepatic impairment, should be closely monitored for signs and symptoms indicative of these conditions. Additionally, patients transitioning from other systemic corticosteroids may experience symptoms of steroid withdrawal; therefore, it is recommended to taper slowly from corticosteroids with high systemic effects and to monitor for withdrawal symptoms and the unmasking of allergies, such as rhinitis and eczema.

There is an increased risk of immunosuppression and subsequent infections, including viral, bacterial, fungal, protozoal, and helminthic infections. This includes potentially fatal infections such as varicella and measles. Patients should be monitored for new or worsening infections, and consideration should be given to discontinuing 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. Screening for hepatitis B infection is also advised.

Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly those being treated for chronic conditions. Furthermore, patients with concomitant conditions such as hypertension and diabetes mellitus should be monitored for unwanted effects associated with corticosteroid use.

Hypersensitivity reactions to budesonide or any of its ingredients have been noted. In cases of overdosage, reports of acute toxicity and/or death are rare; however, treatment should consist of immediate gastric lavage or emesis, followed by supportive and symptomatic therapy. Prolonged use of excessive doses of corticosteroids may lead to systemic effects, including hypercorticism and adrenal axis suppression. In instances of chronic overdosage, particularly in severe disease requiring continuous steroid therapy, a temporary reduction in dosage may be necessary.

Acute toxicity has been observed in animal studies, with single oral doses of 200 mg/kg and 400 mg/kg being lethal in female and male mice, respectively. Signs of acute toxicity included decreased motor activity, piloerection, and generalized edema.

Drug Interactions

CYP3A4 inhibitors, such as ketoconazole and grapefruit juice, have the potential to significantly increase systemic concentrations of budesonide. Co-administration of these agents should be avoided to prevent the risk of adverse effects associated with elevated budesonide levels. Monitoring for signs of increased systemic effects is recommended if exposure to these inhibitors 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 have been established in pediatric patients aged 8 to 17 years who weigh more than 25 kg for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon. The observed safety profile in this population is consistent with that in adults, with no new safety concerns identified.

However, the safety and effectiveness of budesonide have not been established in pediatric patients under 8 years of age for the treatment of mild to moderate active Crohn’s disease. Additionally, the efficacy and safety of budesonide for the maintenance of clinical remission in pediatric patients have not been established. An open-label study assessing the safety and tolerability of budesonide as maintenance treatment in patients aged 5 to 17 years did not demonstrate efficacy for maintaining clinical remission.

It is important to note that systemic corticosteroids, including budesonide, may lead to a reduction in growth velocity in pediatric patients. Furthermore, pediatric patients with Crohn’s disease exhibit a 17% higher mean systemic exposure and cortisol suppression compared to adults with the same condition.

Geriatric Use

Clinical studies of budesonide did not include a sufficient number of patients aged 65 years and older to determine whether this population responds differently compared to younger patients. Among the 651 patients treated with budesonide in these studies, only 17 patients (3%) were aged 65 years or older, with none exceeding 74 years of age.

Other reported clinical experiences have not identified any significant differences in responses between elderly patients and their younger counterparts. However, it is important to note that dose selection for geriatric patients should be approached with caution. It is generally recommended to initiate treatment at the lower end of the dosing range. This recommendation is based on the increased likelihood of diminished hepatic, renal, or cardiac function in elderly patients, as well as the potential for concomitant diseases or other drug therapies that may affect treatment outcomes.

Healthcare providers should closely monitor elderly patients for any adverse effects or changes in therapeutic response when prescribing budesonide.

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, administration of subcutaneous budesonide during organogenesis in pregnant rats and rabbits at doses approximately 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 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 population is unknown; however, 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 miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Budesonide has been shown to be teratogenic and embryolethal in rabbits and rats. In an embryo-fetal development study involving pregnant rats dosed subcutaneously with budesonide during the period of organogenesis from gestation days 6 to 15, effects on fetal development and survival were observed at subcutaneous doses up to approximately 500 mcg/kg (approximately 0.5 times the maximum recommended human dose on a body surface area basis). Similarly, in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, there was an increase in maternal abortion, along with effects on fetal development and a reduction in litter weights at subcutaneous doses up to approximately 25 mcg/kg (approximately 0.05 times the maximum recommended human dose on a body surface area basis).

Maternal toxicity, including a reduction in body weight gain, was noted at subcutaneous doses of 5 mcg/kg in rabbits (approximately 0.01 times the maximum recommended human dose on a body surface area basis) and 500 mcg/kg in rats. In a peri- and post-natal development study, rats dosed subcutaneously with budesonide 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. Specifically, offspring survival was reduced, and surviving offspring exhibited decreased mean body weights at birth and during lactation at exposures of 0.02 times the maximum recommended human dose (on a mg/m² basis at maternal subcutaneous doses of 20 mcg/kg/day and higher). These findings occurred in the presence of maternal toxicity.

Lactation

Lactation studies have not been conducted with oral budesonide, and there is no information available on the effects of the drug on breastfed infants or on milk production. However, one published study indicates that budesonide is present in human milk following maternal inhalation, with infant doses estimated to be approximately 0.3% to 1% of the maternal weight-adjusted dosage. The milk/plasma ratio in this study ranged from 0.4 to 0.5.

Budesonide plasma concentrations were not detected, and no adverse events were reported 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 budesonide and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

The recommended daily dose of oral budesonide is significantly higher (up to 9 mg daily) compared to the inhaled form (up to 800 mcg daily) used in the aforementioned study. Assuming a constant coefficient of extrapolation between inhaled and oral doses, exposure to budesonide in nursing children at therapeutic doses may be up to 10 times higher than that from inhalation.

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 and consider individual patient factors when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment.

Hepatic Impairment

Patients with hepatic impairment may experience adverse effects during treatment. It is essential to monitor these individuals closely for signs and symptoms of liver dysfunction. Special attention should be given to pediatric patients and those with compromised liver function, as they may be at an increased risk for complications. Regular assessment of liver function is recommended to ensure patient safety and to guide any necessary adjustments in therapy.

Overdosage

Acute toxicity and fatalities associated with glucocorticoid 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 corticosteroids at excessive doses can lead to systemic effects, including hypercorticism and suppression of the adrenal axis. In cases of chronic overdosage, particularly when treating severe conditions that necessitate ongoing steroid therapy, it may be appropriate to temporarily reduce the dosage to mitigate adverse effects.

Experimental data indicate that single oral doses of 200 mg/kg in female mice and 400 mg/kg in male mice resulted in lethality. Observed signs of acute toxicity in these studies included decreased motor activity, piloerection, and generalized edema. Healthcare professionals should remain vigilant for these symptoms in cases of suspected overdosage and initiate appropriate management strategies promptly.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. In non-teratogenic assessments, budesonide demonstrated no impact on fertility in rats at subcutaneous doses up to 80 mcg/kg, which is approximately 0.07 times the maximum recommended human dose based on body surface area. However, at subcutaneous doses of 20 mcg/kg (approximately 0.02 times the maximum recommended human dose), there was a noted decrease in prenatal viability and viability of pups at birth and during lactation, alongside a reduction in maternal body-weight gain. No adverse effects were recorded at a dose of 5 mcg/kg (approximately 0.005 times the maximum recommended human dose).

Carcinogenicity studies involving budesonide were performed in both rats and mice. A two-year study in Sprague-Dawley rats revealed a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg (approximately 0.05 times the maximum recommended human dose). Additionally, there were increased incidences of primary hepatocellular tumors in male rats at doses of 25 mcg/kg (approximately 0.023 times the maximum recommended human dose) and higher. No tumorigenicity was observed 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 detected at the same oral dose of 50 mcg/kg; however, a statistically significant increase in hepatocellular tumors was noted. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings. In a 91-week study in mice, budesonide did not induce treatment-related carcinogenicity at oral doses up to 200 mcg/kg (approximately 0.1 times the maximum recommended human dose).

Postmarketing Experience

No specific postmarketing experience details have been reported. As such, there are no additional adverse events or rare case reports to summarize at this time.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) to understand the medication's use and potential risks. It is important to inform patients that budesonide may lead to hypercorticism and adrenal axis suppression. If patients are transitioning from systemic corticosteroids to budesonide, they should follow a taper schedule as instructed by their healthcare provider.

Patients should also be made aware that the replacement of systemic corticosteroids with budesonide may unmask previously controlled allergies, such as rhinitis and eczema. Therefore, they should monitor for any resurgence of these symptoms.

Additionally, patients should be cautioned to avoid exposure to individuals with varicella (chicken pox) or measles. They must inform their healthcare provider if they have been exposed to these infections or if they develop any new or worsening infections.

Lastly, patients should be informed that there have been reports of Kaposi’s sarcoma in individuals receiving corticosteroids for chronic conditions. They should be advised to notify their healthcare provider if they experience any signs or symptoms indicative of Kaposi’s sarcoma.

Storage and Handling

The product is supplied in a container that must be kept tightly closed to maintain integrity. It should be stored 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.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)