Budesonide

Description

Budesonide extended-release tablets contain budesonide USP, a synthetic corticosteroid, as the active ingredient. Budesonide, USP is chemically designated as (RS)-11β, 16α, 17, 21 tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde and is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide, USP is C25H34O6, with a molecular weight of 430.54. Budesonide, USP appears as a white to almost white, tasteless, odorless powder that is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in chloroform. Budesonide extended-release is formulated as a delayed and extended-release tablet, coated with a polymer film that disintegrates at or above pH 7. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose 2910, iron oxide black, lactose monohydrate, magnesium stearate, methacrylic acid copolymer types A and B, microcrystalline cellulose, polyethylene glycol 400, polysorbate 80, propylene glycol, sodium starch glycolate Type A, soy lecithin powder, talc, titanium dioxide, and triethyl citrate.

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 symptoms associated with this condition, facilitating the management of their disease.

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.

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 based on the potential for severe allergic reactions in susceptible individuals.

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 glucocorticoid therapy are at an increased risk of immunosuppression, which heightens the likelihood of viral, bacterial, fungal, protozoal, and helminthic infections. This includes 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 such infections arise. The use of budesonide extended-release tablets 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 with budesonide extended-release tablets.

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 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 infections, including viral, bacterial, fungal, protozoal, and helminthic infections. This includes potentially fatal infections such as varicella and measles. It is crucial to monitor patients for new or worsening infections and consider discontinuation of the drug if necessary. 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 advised.

Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly 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 observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Drug Interactions

The concomitant use of cytochrome P450 3A4 inhibitors, such as ketoconazole and grapefruit juice, should be avoided. The interaction may lead to increased systemic effects of corticosteroids, which could result in heightened adverse effects or therapeutic responses.

No specific drug and laboratory test interactions have been identified. Therefore, monitoring for potential effects when using these inhibitors is advisable, although no dosage adjustments are explicitly recommended based on the available data.

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 this medication 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 experiences have not identified significant differences in responses between geriatric patients and their younger counterparts.

In general, budesonide extended-release tablets should be used with caution 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 closely monitor elderly patients for any adverse effects and consider appropriate dose modifications based on individual patient assessments.

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 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 population is unknown; however, it is acknowledged that 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.

Published data suggest that increased disease activity in women with ulcerative colitis is associated with the risk of developing adverse pregnancy outcomes, including preterm delivery, low birth weight infants, and small for gestational age at birth. Additionally, 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, dosing during the period of organogenesis resulted in effects on fetal development and survival at subcutaneous doses up to approximately 500 mcg/kg. Similarly, in pregnant rabbits, dosing during organogenesis led to increased maternal abortion rates and effects on fetal development at doses up to approximately 25 mcg/kg. Maternal toxicity, including reduced body weight gain, was observed 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 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 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 toxicity and fatalities associated with overdosage of glucocorticosteroids 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.

Experimental studies have demonstrated that single oral doses of budesonide at 200 mg/kg and 400 mg/kg were lethal in female and male mice, respectively. Observed signs of acute toxicity in these cases included decreased motor activity, piloerection, and generalized edema, which may serve as indicators of severe adverse effects in humans as well.

Prolonged use of glucocorticosteroids at excessive doses can lead to systemic effects, including hypercorticism and adrenal suppression. Healthcare professionals should monitor patients closely for these potential complications and manage them accordingly.

Nonclinical Toxicology

Budesonide has been evaluated for its potential teratogenic and non-teratogenic effects in nonclinical studies. No information regarding teratogenic effects is available.

In terms of non-teratogenic effects, studies in rats indicated that budesonide did not affect fertility at subcutaneous doses up to 80 mcg/kg, which is approximately 0.07 times the maximum recommended human dose on a body surface area basis. However, at subcutaneous doses of 20 mcg/kg (approximately 0.02 times the maximum recommended human dose on a body surface area basis) and above, 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 observed at a dose of 5 mcg/kg (approximately 0.005 times the maximum recommended human dose on a body surface area basis).

Carcinogenicity studies involving budesonide were conducted 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 on a body surface area basis). 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 on a body surface area basis) 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, budesonide did not induce gliomas at an oral dose of 50 mcg/kg; however, it did result in a statistically significant increase in hepatocellular tumors at the same dose. 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 0.1 times the maximum recommended human dose on a body surface area basis).

Postmarketing Experience

Postmarketing experience has identified several adverse events reported voluntarily or through surveillance programs.

Kaposi’s sarcoma has been observed in individuals receiving corticosteroid therapy, particularly for chronic conditions. Additionally, reactivation of the hepatitis B virus (HBV) has been reported in carriers of HBV during treatment with budesonide extended-release tablets, leading to the potential for the virus to become an active infection.

Cases of amebiasis have also been noted, where latent amebiasis may reactivate during the use of budesonide extended-release tablets. Furthermore, there have been reports of worsening allergies in patients who switch from certain other corticosteroid medications to budesonide extended-release tablets, resulting in a resurgence of allergic symptoms.

Patient Counseling

Advise patients to read the FDA-approved patient labeling (Patient Information) to understand the safe and effective use of budesonide extended-release tablets. It is important to inform patients that these tablets may cause systemic glucocorticosteroid effects, including hypercorticism and adrenal suppression. Patients should be instructed to taper slowly from systemic corticosteroids if transitioning to budesonide extended-release tablets.

Patients should be cautioned to avoid exposure to individuals with varicella (chicken pox) or measles. They must inform their healthcare provider if they are exposed to these infections or if they develop a new or worsening infection. Additionally, patients should be made aware that Kaposi’s sarcoma has been reported in individuals receiving corticosteroids for chronic conditions, and they should notify their healthcare provider if they experience any signs or symptoms of this condition.

Instruct patients to swallow budesonide extended-release tablets whole with water, emphasizing that they should not chew or crush the tablets. Patients should also avoid consuming grapefruit juice during the course of their therapy, as it can increase the levels of budesonide in the blood.

Female patients should be informed that budesonide extended-release tablets may cause fetal harm, and they should notify their healthcare provider if they are pregnant or suspect they may be pregnant. Prior to initiating treatment, patients should disclose all medical conditions to their healthcare provider, including liver problems, plans for surgery, recent exposure to chickenpox or measles, infections (including fungal and Strongyloides infections), family history of diabetes, cataracts, or glaucoma, history of tuberculosis, hypertension, decreased bone mineral density (osteoporosis), stomach ulcers, cerebral malaria, and breastfeeding status.

Patients should also provide a complete list of all medications they are taking, including prescription and over-the-counter drugs, vitamins, and herbal supplements, as interactions may occur. It is particularly important to inform healthcare providers about any other corticosteroid medications being taken for conditions such as allergies or asthma.

Patients should take budesonide extended-release tablets exactly as prescribed, once daily in the morning, with or without food. If a patient takes too much of the medication, they should contact their healthcare provider immediately or go to the nearest hospital emergency room.

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 range of 20° to 25°C (68° to 77°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 Actavis Pharma, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)