Budesonide

Description

Budesonide, the active ingredient in budesonide inhalation suspension, is a corticosteroid with the chemical designation of (RS)-11β, 16α, 17, 21-tetrahydroxypregna-1, 4-diene-3, 20-dione cyclic 16, 17-acetal with butyraldehyde. It is provided as a mixture of two epimers, specifically the 22R and 22S forms. The empirical formula of budesonide is C₂₅H₃₄O₆, and it has a molecular weight of 430.5 g/mol.

Budesonide appears as a white to off-white, tasteless, and odorless powder. It is characterized by its low solubility profile, being practically insoluble in water and heptane, sparingly soluble in ethanol, and freely soluble in chloroform. The partition coefficient between octanol and water at pH 7.4 is 1.6 x 10³.

The budesonide inhalation suspension is a sterile formulation intended for inhalation via a jet nebulizer. Each suspension contains micronized budesonide along with inactive ingredients, including disodium edetate, sodium chloride, sodium citrate dihydrate, citric acid monohydrate, polysorbate 80, and Water for Injection. It is available in three dose strengths: 0.25 mg, 0.5 mg, and 1 mg per 2 mL ampule.

The delivery of budesonide to the lungs is influenced by various patient factors, the specific jet nebulizer used, and the performance of the compressor. In vitro studies using the Pari-LC-Jet Plus Nebulizer/Pari Master compressor system have shown that the mean delivered dose at the mouthpiece is approximately 17% of the nominal dose at a mean flow rate of 5.5 L/min, with a mean nebulization time of 5 minutes or less. Budesonide inhalation suspension should be administered using jet nebulizers at appropriate flow rates, utilizing either face masks or mouthpieces.

Uses and Indications

Budesonide inhalation suspension is indicated for the maintenance treatment of asthma and as prophylactic therapy in pediatric patients aged 12 months to 8 years. This medication is not indicated for the relief of acute bronchospasm.

There are no teratogenic or nonteratogenic effects associated with the use of budesonide inhalation suspension.

Dosage and Administration

The recommended dosing for bronchodilators is 0.5 mg once daily or 0.25 mg twice daily. For inhaled corticosteroids, the recommended dosing is 0.5 mg once daily or 0.25 mg twice daily, with a maximum of 0.5 mg twice daily. Oral corticosteroids may be administered at a dose of 0.5 mg twice daily or 1 mg once daily. In symptomatic children who do not respond to non-steroidal therapy, a starting dose of 0.25 mg once daily may be considered.

If once-daily treatment does not provide adequate control, the total daily dose should be increased and/or administered as a divided dose. Once asthma stability is achieved, it is advised to titrate the dose downwards.

The medication is intended for inhalation use only via compressed air-driven jet nebulizers; it is not suitable for use with ultrasonic devices and is not for injection.

Contraindications

Use of budesonide inhalation suspension is contraindicated in the following situations:

• It should not be used as the primary treatment for status asthmaticus or other acute episodes of asthma that require intensive measures, due to the need for immediate and effective bronchodilation in such cases.

• Patients with a known hypersensitivity to any of the ingredients in budesonide inhalation suspension should not use this product, as it may lead to severe allergic reactions.

Warnings and Precautions

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur in patients using budesonide inhalation suspension. Healthcare professionals should monitor patients periodically for signs of adverse effects on the oral cavity and advise them to rinse their mouth following inhalation to mitigate this risk.

Budesonide inhalation suspension is not indicated for the relief of acute bronchospasm. Therefore, it should not be used in the management of acute asthma episodes or the deterioration of disease.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. If any of these reactions occur, the use of budesonide inhalation suspension should be discontinued immediately.

Immunosuppression is a potential concern, particularly in patients with existing infections such as tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is advised when prescribing budesonide inhalation suspension to these patients, as they may experience a more serious or even fatal course of chickenpox or measles.

When transferring patients from systemic corticosteroid therapy to budesonide inhalation suspension, there is a risk of impaired adrenal function. It is essential to taper patients slowly from oral steroids to minimize this risk.

Hypercorticism and adrenal suppression may occur, particularly with very high dosages or in susceptible individuals. Should these changes arise, the dosage of budesonide inhalation suspension should be reduced gradually.

Long-term administration of budesonide inhalation suspension may lead to a reduction in bone mineral density. Therefore, it is crucial to monitor patients who have major risk factors for decreased bone mineral content.

In pediatric patients, growth should be closely monitored during treatment with budesonide inhalation suspension to ensure that any potential effects on growth are identified and managed appropriately.

Patients should be monitored for the development of glaucoma and cataracts, as close observation is warranted in these cases.

Paradoxical bronchospasm may occur in some patients. If this reaction is observed, budesonide inhalation suspension should be discontinued, and alternative therapy should be initiated.

Healthcare professionals should remain vigilant for eosinophilic conditions, including Churg-Strauss syndrome, in patients receiving budesonide inhalation suspension.

To ensure patient safety, it is recommended to monitor patients with major risk factors for decreased bone mineral content, track the growth of pediatric patients, and conduct close monitoring for glaucoma and cataracts throughout the course of treatment.

Side Effects

Patients receiving budesonide inhalation suspension may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Most common adverse reactions include respiratory infections, rhinitis, coughing, otitis media, viral infections, moniliasis, gastroenteritis, vomiting, diarrhea, abdominal pain, ear infections, epistaxis, conjunctivitis, and rash. These reactions were observed in clinical trials and may vary in incidence among patients.

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur. It is advisable to monitor patients periodically for signs of adverse effects on the oral cavity and to instruct them to rinse their mouths following inhalation to mitigate this risk.

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm. If any of these reactions occur, it is essential to discontinue budesonide inhalation suspension immediately. Additionally, patients may experience a deterioration of disease and acute asthma episodes; therefore, this medication should not be used for the relief of acute bronchospasm.

Immunosuppression is another concern, as there is a potential for worsening of existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is advised when prescribing budesonide inhalation suspension to patients with these conditions. Furthermore, susceptible patients may experience a more serious or even fatal course of chickenpox or measles.

When transferring patients from systemic corticosteroid therapy to budesonide inhalation suspension, there is a risk of impaired adrenal function. It is recommended to taper patients slowly from oral steroids to minimize this risk. Hypercorticism and adrenal suppression may occur, particularly with very high dosages or in susceptible individuals; if such changes are observed, a gradual reduction of the medication is necessary.

Long-term administration of budesonide inhalation suspension may lead to a reduction in bone mineral density, necessitating monitoring in patients with major risk factors for decreased bone mineral content. Additionally, the growth of pediatric patients should be closely monitored, as a dose-dependent effect on growth has been noted, with reductions in growth velocity associated with inhaled corticosteroids. The long-term implications of this reduction in growth velocity remain unknown.

Patients should also be monitored for the development of glaucoma and cataracts, as close observation is warranted in these cases. Paradoxical bronchospasm has been reported; if this occurs, budesonide inhalation suspension should be discontinued, and alternative therapy should be initiated.

Lastly, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension compared to those receiving placebo, highlighting the importance of vigilance in monitoring for this adverse reaction. Eosinophilic conditions, including Churg-Strauss syndrome, should also be considered, and healthcare providers should remain alert to these potential complications.

Drug Interactions

The concomitant use of strong Cytochrome P450 3A4 inhibitors, such as ritonavir, should be approached with caution. This combination may lead to an increase in systemic corticosteroid effects, which could heighten the risk of adverse reactions associated with corticosteroid therapy.

Monitoring for signs of increased corticosteroid effects is recommended when these agents are used together. No specific dosage adjustments are provided; however, clinicians should consider the potential for enhanced effects and adjust treatment accordingly based on the patient's clinical response.

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

Safety and effectiveness of budesonide inhalation suspension in pediatric patients aged six months to 12 months have been evaluated but not established. In children aged 12 months to 8 years, safety and effectiveness have been established. A 12-week study involving 141 pediatric patients aged 6 to 12 months with mild to moderate asthma or recurrent/persistent wheezing assessed the effects of budesonide inhalation suspension. Patients were randomized to receive either 0.5 mg or 1 mg of budesonide or placebo once daily.

Adrenal-axis function was evaluated using an ACTH stimulation test at the study's start and end, revealing no significant adrenal suppression in patients receiving budesonide compared to placebo. However, pneumonia occurred more frequently in patients treated with budesonide. A dose-dependent effect on growth was observed; infants in the placebo group experienced an average growth of 3.7 cm over 12 weeks, while those receiving budesonide showed growth of 3.5 cm and 3.1 cm in the 0.5 mg and 1 mg groups, respectively. These findings suggest that budesonide inhalation suspension may lead to systemic effects, consistent with growth suppression noted in other studies involving inhaled corticosteroids.

Controlled clinical studies indicate that inhaled corticosteroids can reduce growth velocity in pediatric patients, with a mean reduction of approximately one centimeter per year, influenced by dose and duration of exposure. The long-term implications of this reduction on final adult height remain unknown, and the potential for "catch up" growth after discontinuation of treatment has not been adequately studied. In a separate study of asthmatic children aged 5 to 12 years, those treated with budesonide via a dry powder inhaler at a dose of 200 mcg twice daily experienced a 1.1-centimeter reduction in growth compared to placebo after one year.

Routine monitoring of growth in pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, is recommended. The potential growth effects of prolonged treatment should be carefully weighed against the clinical benefits and the risks associated with alternative therapies. To minimize systemic effects, each patient should be titrated to the lowest effective dose.

Geriatric Use

In clinical trials involving budesonide inhalation suspension, 30% of the 215 patients studied were aged 65 years or older, with 10% being 75 years of age or older. The data indicate that there were no overall differences in safety profiles between elderly patients and their younger counterparts. Furthermore, additional clinical and medical surveillance has not revealed any significant differences in responses to treatment between geriatric patients and younger individuals.

Given the lack of observed differences in safety and efficacy, no specific dosage adjustments are recommended for elderly patients. However, healthcare providers should remain vigilant in monitoring this population for any potential adverse effects, as individual responses may vary. It is essential to consider the overall health status and comorbidities of geriatric patients when prescribing budesonide inhalation suspension.

Pregnancy

There are no adequate well-controlled studies of budesonide inhalation suspension in pregnant patients. However, available data from studies involving the active ingredient, budesonide, suggest that inhaled budesonide does not increase the risk of fetal abnormalities when administered during pregnancy. A large population-based prospective cohort study indicated that the rate of congenital malformations among infants exposed to inhaled budesonide during early pregnancy was comparable to that of the general population (3.8% vs. 3.5%). Additionally, the incidence of orofacial clefts in infants born to mothers who used inhaled budesonide was similar to expected rates (4 cases vs. 3.3 expected).

Animal reproduction studies have shown that budesonide, when administered subcutaneously, caused structural abnormalities, embryocidal effects, and reduced fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). However, these adverse effects were not observed in rats receiving inhaled doses approximately 2 times the MRHDID. In another study, budesonide resulted in decreased prenatal viability and reduced body weight in offspring at doses less than 0.2 times the MRHDID.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20%, respectively. In women with poorly or moderately controlled asthma, there is an increased risk of perinatal adverse outcomes, including preeclampsia, prematurity, low birth weight, and small for gestational age neonates. Therefore, pregnant women with asthma should be closely monitored, and medication should be adjusted as necessary to maintain optimal asthma control.

There are no well-controlled human studies investigating the effects of budesonide inhalation suspension during labor and delivery. Given the potential risks associated with poorly controlled asthma during pregnancy, healthcare providers should weigh the benefits of asthma control against any potential risks when considering the use of budesonide inhalation suspension in pregnant patients.

Lactation

Budesonide inhalation suspension is present in human milk; however, there are no available data on its effects on breastfed infants or on milk production. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for budesonide inhalation suspension and any potential adverse effects on the breastfed infant from the medication or from the underlying maternal condition.

Data from human studies involving budesonide delivered via dry powder inhaler suggest that the total daily oral dose of budesonide available in breast milk to the infant is approximately 0.3% to 1% of the dose inhaled by the mother.

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 assessment of renal function may be warranted to ensure safe and effective use of the medication in patients with reduced kidney function.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions 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

The potential for acute toxic effects following an overdose of budesonide inhalation suspension is considered low. However, it is important for healthcare professionals to be aware of the implications of excessive dosing, particularly with prolonged use of inhaled corticosteroids.

In cases where inhaled corticosteroids are administered at excessive doses over an extended duration, systemic corticosteroid effects may manifest. These effects can include hypercorticism, which is characterized by symptoms such as weight gain, hypertension, and glucose intolerance, as well as growth suppression in pediatric patients.

Management of an overdose should focus on monitoring the patient for any signs of systemic corticosteroid effects. If symptoms of hypercorticism or growth suppression are observed, appropriate clinical interventions should be initiated. It is advisable to consult relevant clinical guidelines and consider the patient's overall health status when determining the course of action.

Nonclinical Toxicology

In a two-year study conducted in Sprague-Dawley rats, budesonide was associated with a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg, which corresponds to approximately 0.5 and 0.1 times the maximum recommended human daily intravenous dose (MRHDID) in adults and children aged 12 months to 8 years, respectively, on a mcg/m² basis. No tumorigenicity was observed in male rats at oral doses up to 25 mcg/kg (approximately 0.2 and 0.04 times the MRHDID) and in female rats at oral doses up to 50 mcg/kg.

In two additional two-year studies involving male Fischer and Sprague-Dawley rats, budesonide did not induce gliomas at an oral dose of 50 mcg/kg. However, a statistically significant increase in the incidence of hepatocellular tumors was noted in male Sprague-Dawley rats at the same dose. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings in these studies. In a separate 91-week study in mice, budesonide did not demonstrate any treatment-related carcinogenicity at oral doses up to 200 mcg/kg, which is approximately equivalent to and 0.1 times the MRHDID.

Budesonide was evaluated for mutagenicity and clastogenicity in six different test systems, including the Ames Salmonella/microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hepatocyte culture. The results indicated that budesonide was neither mutagenic nor clastogenic.

Fertility and reproductive performance were not adversely affected in rats at subcutaneous doses up to 80 mcg/kg, which is approximately equivalent to the MRHDID in adults on a mcg/m² basis. However, a decrease in prenatal viability and viability of pups at birth and during lactation was observed at subcutaneous doses of 20 mcg/kg and above, approximately 0.2 times the MRHDID. No such effects were noted at a dose of 5 mcg/kg, which corresponds to approximately 0.05 times the MRHDID in adults on a mcg/m² basis.

Postmarketing Experience

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported following the use of budesonide inhalation suspension. Patients receiving immunosuppressant doses of corticosteroids are advised to avoid exposure to chickenpox or measles and to consult their physician promptly if exposed.

There have been observations of potential worsening of existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. The use of budesonide inhalation suspension may lead to systemic corticosteroid effects, such as hypercorticism and adrenal suppression. Reports indicate that deaths due to adrenal insufficiency have occurred during and after transitioning from systemic corticosteroids.

Additionally, the use of corticosteroids may increase the risk of decreased bone mineral density (BMD), particularly in susceptible patients. In pediatric patients, orally inhaled corticosteroids, including budesonide inhalation suspension, may result in a reduction in growth velocity. Long-term use of inhaled corticosteroids has been associated with an increased risk of ocular complications, such as cataracts and glaucoma, warranting regular eye examinations.

Fungal infections, specifically thrush (candida), have been reported in the mouth and throat. There are also reports of worsening asthma or sudden asthma attacks. Allergic reactions, including skin rash, redness or swelling, severe itching, facial swelling, difficulty breathing or swallowing, chest pain, and feelings of anxiety, have been documented.

Effects on the immune system and an increased likelihood of infections have been noted. Symptoms indicative of adrenal insufficiency, such as tiredness, weakness, nausea, vomiting, and low blood pressure, have been reported. Decreased bone mineral density and delayed growth problems have also been observed. Eye issues, including glaucoma and cataracts, have been documented, along with increased wheezing immediately following the administration of budesonide inhalation suspension.

Patient Counseling

Patients should be advised that budesonide inhalation suspension must be administered using a jet nebulizer connected to a compressor that provides adequate airflow, equipped with either a mouthpiece or a suitable face mask. It is important to inform patients that ultrasonic nebulizers are not appropriate for the administration of budesonide inhalation suspension and should not be used.

Patients should be made aware of the potential for localized infections with Candida albicans in the mouth and pharynx. In the event that oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic antifungal therapy while continuing therapy with budesonide inhalation suspension. However, there may be instances where therapy with budesonide inhalation suspension needs to be temporarily interrupted under close medical supervision. Patients are advised to rinse their mouths after inhalation to help mitigate this risk.

It is crucial to inform patients that budesonide inhalation suspension is not intended to relieve acute asthma symptoms, and extra doses should not be used for this purpose. Acute symptoms should be managed with an inhaled, short-acting beta-agonist, such as albuterol. Patients should be instructed to notify their healthcare professional immediately if they experience any of the following: decreasing effectiveness of inhaled, short-acting beta-agonists; an increased need for inhalations of inhaled, short-acting beta-agonists; or a significant decrease in lung function as outlined by their physician.

Patients should not discontinue therapy with budesonide inhalation suspension without consulting their healthcare provider, as symptoms may recur following discontinuation. Additionally, hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported with the use of budesonide inhalation suspension. Patients should be advised to discontinue the medication if such reactions occur.

For patients on immunosuppressant doses of corticosteroids, it is important to warn them to avoid exposure to chickenpox or measles. If exposure occurs, they should consult their physician without delay, especially if the child has not had chickenpox or has not been properly vaccinated. Patients should also be informed of the potential for worsening existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

Patients should be made aware that budesonide inhalation suspension may lead to systemic corticosteroid effects, including hypercorticism and adrenal suppression. They should be informed that there have been reports of deaths due to adrenal insufficiency during and after transitioning from systemic corticosteroids. Therefore, patients should taper slowly from systemic corticosteroids when transitioning to budesonide inhalation suspension.

Patients at increased risk for decreased bone mineral density (BMD) should be advised that the use of corticosteroids may further elevate this risk. Furthermore, patients should be informed that orally inhaled corticosteroids, including budesonide inhalation suspension, may reduce growth velocity in pediatric patients. Healthcare professionals should closely monitor the growth of children and adolescents receiving corticosteroids by any route.

Long-term use of inhaled corticosteroids may increase the risk of certain eye problems, such as cataracts or glaucoma; therefore, regular eye examinations should be considered. Patients should be advised to use budesonide inhalation suspension at regular intervals, either once or twice a day, as its effectiveness is contingent upon consistent use. Maximum benefit may not be realized for 4 to 6 weeks or longer after initiating treatment. If symptoms do not improve within this timeframe or if the condition worsens, patients should be instructed to contact their healthcare professional.

Storage and Handling

Budesonide inhalation suspension is supplied in ampules and should be stored upright at a controlled room temperature of 20°C to 25°C (68°F to 77°F), ensuring protection from light. The product must not be frozen.

Once an envelope has been opened, the shelf life of the unused ampules is limited to 2 weeks, provided they are kept protected from light and returned to the aluminum foil envelope after opening. Any opened ampule should be used promptly. Prior to use, it is recommended to gently shake the ampule in a circular motion.

It is essential to keep this product out of reach of children.

Additional Clinical Information

Patients using budesonide inhalation suspension should be advised to rinse their mouths after each inhalation to minimize local side effects. It is crucial for patients to contact their physician immediately if they experience asthma episodes that do not respond to their usual bronchodilator doses during treatment.

Clinicians should be aware that patients previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be at increased risk for adrenal insufficiency when transitioning from systemic corticosteroids to inhaled corticosteroids. Patients are encouraged to carry a medical identification card indicating their potential need for supplementary systemic corticosteroids during periods of stress or severe asthma attacks. Additionally, those requiring oral corticosteroids should be weaned off slowly after starting budesonide inhalation suspension, with careful monitoring of lung function (FEV or AM PEF), beta-agonist use, and asthma symptoms during this withdrawal process.

FDA Insert (PDF)

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

View full prescribing information (PDF)