Budesonide

Description

Budesonide extended-release tablets contain budesonide, a synthetic corticosteroid, as the active ingredient. Budesonide is chemically designated as (R,S)-11ß,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dionecyclic-16,17-acetal with butyraldehyde and is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C25H34O6, and its molecular weight is 430.53 g/mol. Budesonide, USP appears as a white or almost white crystalline odorless powder that is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in chloroform. The formulation is 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, lactose monohydrate, magnesium stearate, methacrylic acid copolymer type A and type B, microcrystalline cellulose, polyethylene glycol, polydextrose, talc, titanium dioxide, triacetin, 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.

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

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 its ingredients.

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. Regular monitoring for signs of infection is also advised, with a recommendation to discontinue the medication if any new or worsening infections are detected.

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 warranting attention include hypercorticism and adrenal suppression, which may occur during 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. 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, patients with known hypersensitivity to budesonide or any of the ingredients in budesonide extended-release tablets should not use this medication.

Drug Interactions

The concomitant use of cytochrome P450 3A4 inhibitors, such as ketoconazole and grapefruit juice, is contraindicated due to the potential for increased systemic corticosteroid effects. This interaction may lead to an enhanced risk of corticosteroid-related adverse effects.

It is advisable to monitor patients closely for signs of increased corticosteroid activity and consider dosage adjustments of corticosteroids if these inhibitors are used concurrently.

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 compared to 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 resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities at doses of 0.5 times and 0.05 times, respectively, the maximum recommended human dose. Maternal toxicity was also observed 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, but it is generally accepted 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 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 monitored for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting.

Budesonide has been shown to be teratogenic and embryolethal in animal studies. In pregnant rats, administration during the period of organogenesis resulted in adverse effects on fetal development and survival at 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 noted at lower doses in both species.

In a peri- and postnatal 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 doses of 20 mcg/kg/day and higher, in the presence of maternal toxicity. These findings underscore the need for careful consideration when prescribing budesonide to pregnant patients.

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 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 for budesonide in this context ranged between 0.4 and 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 note that the recommended daily dose of budesonide extended-release tablets (9 mg) is significantly higher than the maximum dose of inhaled budesonide (up to 800 mcg daily) used in the aforementioned study. The maximum plasma concentration of budesonide following a 9 mg daily dose of oral budesonide is approximately 5 to 10 nmol/L, which is up to 10 times higher than the 1 to 2 nmol/L observed for the inhaled form at steady state.

Given these considerations, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for budesonide extended-release tablets and any potential adverse effects on the breastfed infant. Assuming the coefficient of extrapolation between inhaled and oral doses is constant, 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 in female mice and 400 mg/kg in male mice resulted in lethality. Observed signs of acute toxicity in these cases included decreased motor activity, piloerection, and generalized edema.

Prolonged use of glucocorticosteroids at excessive doses may 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

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, there were increased incidences of primary hepatocellular tumors in male rats at doses of 25 mcg/kg and above, which corresponds to approximately 0.023 times the maximum recommended human dose on a body surface area basis. No tumorigenicity was noted 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 the incidence of hepatocellular tumors at the same dose. The concurrent reference glucocorticosteroids, 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 (TK +/-) test, the human lymphocyte chromosome aberration test, the Drosophila melanogaster sex-linked recessive lethality test, the rat hepatocyte unscheduled DNA synthesis (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 0.07 times the maximum recommended human dose on a body surface area basis. However, it was associated with a decrease in prenatal viability and viability of pups at birth and during lactation, as well as a reduction in maternal body weight gain, at subcutaneous doses of 20 mcg/kg and above, which is approximately 0.02 times the maximum recommended human dose on a body surface area basis. No such 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.

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of budesonide extended-release tablets, reported voluntarily or through surveillance programs.

Kaposi’s sarcoma has been observed in individuals receiving corticosteroid therapy, particularly for chronic conditions. There is a noted decrease in the body’s ability to fight infections (immunosuppression), which may lead to an increased risk of infections. Corticosteroid medications, including budesonide, are known to lower immune system efficacy, resulting in susceptibility to infections caused by various pathogens, including viruses, bacteria, fungi, protozoa, and certain parasites. These infections can range from mild to severe and may result in fatal outcomes.

Specific infections of concern include the reactivation of latent tuberculosis in patients undergoing treatment with budesonide. Additionally, individuals who have not previously contracted chickenpox or measles are advised to avoid contact with infected persons, as corticosteroid therapy may increase susceptibility to these diseases.

Reactivation of Hepatitis B virus (HBV) has also been reported in carriers during treatment with budesonide, as well as the potential for latent amebiasis to become active. Furthermore, patients switching from other corticosteroid medications for allergy treatment to budesonide may experience a resurgence of allergy symptoms.

Patient Counseling

Patients should be advised 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. If patients are transitioning from systemic corticosteroids to budesonide extended-release tablets, they should be instructed to taper the previous medication slowly.

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 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, and they should notify their healthcare provider if they experience any signs or symptoms associated with this condition.

It is essential to instruct patients to swallow budesonide extended-release tablets whole with water, without chewing or crushing them. They 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, any 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 used 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. In the event of an overdose, patients should contact their healthcare provider immediately or go to the nearest hospital emergency room. Lastly, patients should be encouraged to report any side effects that are bothersome or persistent to their healthcare provider.

Storage and Handling

The product is supplied in a tightly closed container that is light-resistant, adhering to the specifications outlined in the United States Pharmacopeia (USP). It is essential to dispense the product in a container that features a child-resistant closure to ensure safety.

Storage conditions require the product to be maintained at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Additionally, the container must be protected from light and moisture to preserve the integrity of the product.

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 Mylan Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)