Budesonide

Description

Budesonide extended-release tablets are formulated for oral administration and contain budesonide, a synthetic corticosteroid, as the active ingredient. Chemically, budesonide is 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 tablets are characterized as white to off-white, odorless, crystalline powders that are practically insoluble in water, sparingly soluble in alcohol, and freely soluble in chloroform. Budesonide extended-release tablets are designed as delayed and extended-release formulations, 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

Budesonide extended-release tablets are indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. This medication is specifically designed for individuals experiencing this condition, providing a targeted therapeutic approach to manage symptoms and promote remission.

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.

Healthcare professionals should monitor patients for efficacy and tolerability during this period, adjusting treatment as necessary based on clinical response.

Contraindications

Use of budesonide extended-release tablets is contraindicated in patients with a known hypersensitivity to budesonide or any of the excipients contained in the formulation. This contraindication is essential to prevent potential allergic reactions that may arise from exposure to these substances.

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 budesonide extended-release tablets, 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.

Side Effects

Patients receiving budesonide extended-release tablets may experience a range of adverse reactions. The most common adverse reactions reported include headache, nausea, decreased blood cortisol levels, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infections, arthralgia, and constipation.

Serious adverse reactions may include hypercorticism and adrenal suppression, which can occur with treatment. It is essential to monitor patients for signs and symptoms indicative of these conditions. Additionally, when transferring patients from systemic glucocorticoids to budesonide extended-release tablets, there is a risk of impaired adrenal function. Therefore, it is recommended to taper patients slowly from systemic corticosteroids to mitigate this risk.

Patients may also experience immunosuppression, leading to an increased risk of various infections, including viral, bacterial, fungal, protozoal, and helminthic infections. This includes potentially fatal infections such as varicella and measles. Continuous monitoring for new or worsening infections is advised, and consideration should be given to drug discontinuation if such infections arise. Budesonide extended-release tablets should be avoided in patients with active fungal infections, Strongyloides infestation, cerebral malaria, and ocular herpes simplex. Screening for hepatitis B infection is also recommended prior to treatment.

Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly in those treated for chronic conditions. Furthermore, known hypersensitivity to budesonide or any of its ingredients is a contraindication for use.

In infants born to mothers who received corticosteroids during pregnancy, hypoadrenalism may occur. These infants should be closely monitored for signs of hypoadrenalism, which may include poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Drug Interactions

Co-administration of this medication with cytochrome P450 3A4 inhibitors, such as ketoconazole and grapefruit juice, is contraindicated. The interaction may lead to increased systemic corticosteroid effects, which could result in an elevated risk of adverse reactions associated with corticosteroid use.

It is advisable to monitor patients closely for signs of increased corticosteroid effects if exposure to these inhibitors cannot be avoided. Adjustments to the dosage of the corticosteroid may be necessary based on clinical response and tolerance.

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 extended-release tablets in pediatric patients have not been established. It is important to note that glucocorticosteroids, including budesonide, may lead to a reduction in growth velocity in this population. Healthcare professionals should consider these factors when prescribing budesonide to children and adolescents.

Geriatric Use

Clinical studies of budesonide extended-release tablets 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 geriatric patients and their younger counterparts.

In general, budesonide extended-release tablets should be used cautiously in elderly 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 affect treatment outcomes. Healthcare providers are advised to monitor elderly patients closely and consider potential dose adjustments based on individual health status and response to therapy.

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 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 observed in both species at these dose levels. Based on these 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. Increased disease activity in women with ulcerative colitis has been 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 embryofetal development study in pregnant rats, subcutaneous doses of budesonide during organogenesis resulted in effects on fetal development and survival at doses up to approximately 500 mcg/kg. In pregnant rabbits, similar dosing led to increased maternal abortion rates and effects on fetal development, with reductions in litter weights observed 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 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 0.02 times the maximum recommended human dose. These findings occurred in the presence of maternal toxicity.

Lactation

Lactation studies have not been conducted with budesonide extended-release tablets or other oral 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, resulting in infant doses approximately 0.3% to 1% of the maternal weight-adjusted dosage, 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 budesonide extended-release tablets and any potential adverse effects on the breastfed infant from the medication or from the underlying maternal condition.

The recommended daily dose of budesonide extended-release tablets is higher (9 mg daily) compared to inhaled budesonide (up to 800 mcg daily) used in the aforementioned study. Assuming the coefficient of extrapolation between inhaled and oral doses is constant across all dose levels, budesonide exposure to the nursing child at therapeutic doses of budesonide extended-release tablets may be up to 10 times higher than that from inhaled budesonide.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular monitoring of renal function may be warranted in patients with reduced kidney function to ensure safety and efficacy.

Hepatic Impairment

Patients with moderate to severe liver disease should be closely monitored for increased signs and/or symptoms of hypercorticism. In such cases, it may be necessary to consider discontinuing the use of budesonide extended-release tablets. Regular assessment of liver function is recommended to ensure patient safety and to determine the appropriateness of continued therapy.

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 that require ongoing steroid therapy, a temporary reduction in dosage may be warranted to mitigate adverse effects.

Experimental studies have demonstrated that single oral doses of budesonide at 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. These findings underscore the importance of careful dosing and monitoring in clinical practice to prevent potential overdose scenarios.

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, 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 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 again 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 test, the human lymphocyte chromosome aberration test, the Drosophila melanogaster sex-linked recessive lethality test, the rat hepatocyte unscheduled DNA synthesis 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 proper use and potential risks associated with budesonide extended-release tablets. It is important for healthcare providers to communicate that this information is intended to aid in the safe and effective use of the medication.

Patients should be informed that budesonide extended-release tablets may lead to systemic glucocorticosteroid effects, including hypercorticism and adrenal suppression. If patients are transitioning from systemic corticosteroids to budesonide extended-release tablets, they should be instructed to taper the previous corticosteroids slowly.

Healthcare providers should counsel patients to avoid exposure to individuals with varicella (chicken pox) or measles. Patients must be encouraged to inform their healthcare provider if they have been exposed to these infections or if they develop any new or worsening infections.

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

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

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 Budesonide as submitted by Oceanside Pharmaceuticals. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)