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, 22R and 22S. The empirical formula of budesonide is C25H34O6, and it has a molecular weight of 430.5.

This compound appears as a white or almost white crystalline powder that is practically insoluble in water, sparingly soluble in ethanol, and freely soluble in methylene chloride. Budesonide inhalation suspension is formulated as a sterile suspension intended for inhalation via jet nebulizer. Each ampule contains micronized budesonide along with inactive ingredients, including citric acid, edetate disodium dihydrate, polysorbate 80, sodium chloride, sodium citrate, and water for injection.

The product is available in two dose strengths: 0.25 mg and 0.5 mg per 2 mL ampule. The amount of budesonide delivered to the lungs is influenced by patient-specific factors, the type of jet nebulizer used, and the performance of the compressor. In in vitro studies using the Pari-LC-Jet Plus Nebulizer/Pari Master compressor system, the mean delivered dose at the mouthpiece was 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 drug is not indicated for the relief of acute bronchospasm. There are no teratogenic or nonteratogenic effects associated with its use.

Dosage and Administration

The initial dosing regimen should commence with the lowest recommended dose tailored to the specific treatment modality. For patients utilizing bronchodilators alone, the starting dose is 0.5 mg once daily or 0.25 mg twice daily. In the case of inhaled corticosteroids, the recommended initiation dose is 0.5 mg once daily or 0.25 mg twice daily, with the possibility of increasing to a maximum of 0.5 mg twice daily based on clinical response. For oral corticosteroids, the starting dose is 0.5 mg administered twice daily.

In symptomatic children who do not respond adequately to non-steroidal therapy, a starting dose of 0.25 mg once daily may be considered. Should once-daily treatment fail to achieve sufficient control of symptoms, the total daily dose may be increased and/or divided into multiple doses. Once asthma stability is attained, it is advisable to titrate the dose downwards to the lowest effective level.

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

Contraindications

Use of budesonide inhalation suspension is contraindicated in patients with hypersensitivity to any of its ingredients. Additionally, it should not be used as a primary treatment for status asthmaticus or other acute episodes of asthma that require intensive measures.

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. It is advisable to instruct patients to rinse their mouths following inhalation to mitigate this risk.

Budesonide inhalation suspension is not indicated for the relief of acute bronchospasm. Caution should be exercised to avoid its use in patients experiencing acute asthma episodes, as this may lead to deterioration of the disease.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported with the use of budesonide inhalation suspension. Should any of these reactions occur, the medication must 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. The use of budesonide inhalation suspension in these patients should be approached with caution, as there is a risk of a more serious or even fatal course of chickenpox or measles in susceptible individuals.

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

Hypercorticism and adrenal suppression may occur, particularly with very high dosages or in susceptible individuals at regular dosages. If such changes are observed, 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 monitored closely during treatment with budesonide inhalation suspension to ensure that any potential effects on growth are identified and managed appropriately.

Patients should also 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 and Churg-Strauss syndrome in patients receiving budesonide inhalation suspension, as these conditions may arise during treatment.

Monitoring parameters include assessing bone mineral density in at-risk patients, tracking growth in pediatric patients, and conducting close evaluations for glaucoma and cataracts. If hypersensitivity reactions or paradoxical bronchospasm occur, the medication should be discontinued, and appropriate alternative therapies should be considered.

Side Effects

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

Most commonly reported 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 postmarketing experiences.

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur. It is recommended that patients be monitored periodically for signs of adverse effects on the oral cavity, and they should be advised to rinse their mouths following inhalation to mitigate this risk.

Patients should be cautioned against using budesonide inhalation suspension for the relief of acute bronchospasm, as it does not provide this benefit and may lead to deterioration of disease or acute asthma episodes.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. If any of these reactions occur, it is advised to discontinue the use of budesonide inhalation suspension immediately.

Immunosuppression is a potential concern, as the use of budesonide may worsen existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is advised when prescribing to patients with these conditions, as a more serious or even fatal course of chickenpox or measles can occur in susceptible individuals.

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

Hypercorticism and adrenal suppression may occur, particularly with very high dosages or at regular dosages in susceptible individuals. If such changes are observed, a gradual reduction of budesonide inhalation suspension is recommended.

Long-term administration of budesonide may lead to a reduction in bone mineral density; therefore, patients with major risk factors for decreased bone mineral content should be monitored closely.

In pediatric patients, growth should be monitored regularly to assess any potential effects on development.

Close monitoring for glaucoma and cataracts is warranted in patients using budesonide inhalation suspension, as these conditions may develop.

Paradoxical bronchospasm has been reported; if this occurs, it is essential to discontinue budesonide inhalation suspension and consider alternative therapies.

Finally, healthcare providers should remain vigilant for eosinophilic conditions and Churg-Strauss syndrome in patients receiving this treatment.

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.

It is advisable to monitor patients closely for signs of increased corticosteroid effects and consider dosage adjustments as necessary to mitigate potential risks.

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 adrenal-axis function using an ACTH stimulation test. The mean changes from baseline indicated no adrenal suppression in patients receiving budesonide inhalation suspension compared to placebo; however, 7 patients experienced a shift from normal to subnormal stimulated cortisol levels by Week 12.

Pneumonia occurred more frequently in patients treated with budesonide inhalation suspension than in those receiving placebo. A dose-dependent effect on growth was observed, with infants in the placebo arm experiencing an average growth of 3.7 cm over 12 weeks, compared to 3.5 cm and 3.1 cm in the 0.5 mg and 1 mg budesonide inhalation suspension arms, respectively. These findings suggest that the use of budesonide inhalation suspension in infants aged 6 to 12 months may lead to systemic effects, including growth suppression, consistent with other studies on inhaled corticosteroids.

Controlled clinical studies indicate that inhaled corticosteroids can reduce growth velocity in pediatric patients, with an average reduction of approximately one centimeter per year. 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 study of asthmatic children aged 5 to 12 years, those treated with budesonide via a dry powder inhaler 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 (e.g., via stadiometry). 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 women. However, published studies have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy. A large population-based prospective cohort study indicated no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy, with the rate of recorded congenital malformations among infants born to mothers using inhaled budesonide being similar to the general population rate (3.8% vs. 3.5%). Additionally, the number of infants born with orofacial clefts after exposure to inhaled budesonide was comparable to the expected number in the normal population (4 children vs. 3.3).

In animal reproduction studies, budesonide has been associated with structural abnormalities, embryocidal effects, and reduced fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). Notably, these adverse effects were not observed in rats receiving inhaled doses approximately 2 times the MRHDID. It is important to consider that experience with oral corticosteroids suggests that rodents may be more susceptible to structural abnormalities from corticosteroid exposure than humans.

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 several perinatal adverse outcomes, including preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. 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. In a fertility and reproduction study, budesonide caused a decrease in prenatal viability and viability in the pups at birth and during lactation at doses 0.2 times the MRHDID. In an embryo-fetal development study in pregnant rabbits, budesonide produced fetal loss, decreased fetal weight, and skeletal abnormalities at doses 0.5 times the MRHDID. Similarly, in pregnant rats, budesonide produced adverse fetal effects at doses approximately 5 times the MRHDID, while no structural abnormalities or embryocidal effects were seen at doses approximately 2 times the MRHDID. Budesonide had no effects on delivery in a peri-and post-natal development study, but it did affect the growth and development of offspring, with reduced survival and decreased mean body weights at doses less than 0.2 times the MRHDID and higher.

Lactation

Budesonide is excreted in human milk; however, the effects on breastfed infants and on milk production are unknown. There are no adequate well-controlled studies of budesonide inhalation suspension in nursing mothers.

Caution should be exercised when administering budesonide inhalation suspension to lactating mothers, and the potential for excretion in breast milk should be considered when prescribing this medication.

Renal Impairment

There is no specific information regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution when prescribing to patients with renal impairment, as the absence of detailed guidance 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 toxic effects following an overdose of budesonide inhalation suspension are considered to be low. However, it is important for healthcare professionals to be aware of the potential consequences associated with excessive dosing, particularly when inhaled corticosteroids are administered at high doses over extended periods.

Potential Symptoms

In cases of prolonged excessive use, systemic corticosteroid effects may manifest. These can include hypercorticism, characterized by symptoms such as weight gain, hypertension, and glucose intolerance, as well as growth suppression in pediatric patients.

Recommended Actions

In the event of suspected overdose, it is advisable to monitor the patient for any signs of systemic corticosteroid effects. While acute toxicity is unlikely, healthcare providers should remain vigilant and consider the patient's overall clinical picture. If symptoms of hypercorticism or growth suppression are observed, appropriate management strategies should be implemented, which may include dose adjustment or discontinuation of the medication, depending on the severity of the symptoms and the clinical judgment of the healthcare provider.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. Fertility and reproductive performance remained unaffected in rats at subcutaneous doses up to 80 mcg/kg, which is approximately equivalent to the maximum recommended human dose on a mcg/m² basis. However, at subcutaneous doses of 20 mcg/kg and above, approximately 0.2 times the maximum recommended human dose in adults on a mcg/m² basis, there was a noted decrease in prenatal viability and viability of the 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, which is approximately 0.05 times the maximum recommended human dose in adults on a mcg/m² basis.

In a two-year study involving Sprague-Dawley rats, budesonide resulted in a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg, approximately 0.5 and 0.1 times the maximum recommended human dose 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 0.06 times the maximum recommended human dose in adults and children aged 12 months to 8 years, respectively, nor in female rats at oral doses up to 50 mcg/kg, approximately 0.4 and 0.1 times the maximum recommended human dose in adults and children aged 12 months to 8 years, respectively. In two additional two-year studies with male Fischer and Sprague-Dawley rats, budesonide did not induce gliomas at an oral dose of 50 mcg/kg, approximately 0.4 and 0.1 times the maximum recommended human dose in adults and children aged 12 months to 8 years, respectively. However, a statistically significant increase in the incidence of hepatocellular tumors was noted in male Sprague-Dawley rats at the same oral dose of 50 mcg/kg. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings in these studies.

In a 91-week study conducted 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 maximum recommended human dose in adults and children aged 12 months to 8 years. Furthermore, budesonide was not found to be mutagenic or clastogenic 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.

Postmarketing Experience

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported following the use of budesonide inhalation suspension. It is recommended to discontinue the medication if such reactions occur.

There have been observations of immune system effects, with an increased likelihood of infections in patients receiving budesonide inhalation suspension. Symptoms indicative of infection may include fever, pain, aches, chills, fatigue, nausea, and vomiting. Healthcare providers should be informed of any signs of infection during treatment.

Cases of adrenal insufficiency have been reported, characterized by insufficient production of steroid hormones by the adrenal glands. Symptoms may include fatigue, weakness, nausea, vomiting, and low blood pressure.

A decrease in bone mineral density has been noted, and healthcare providers may consider monitoring bone strength during treatment with budesonide inhalation suspension.

Reports of slowed or delayed growth in pediatric patients have been documented, prompting healthcare providers to monitor growth during the course of treatment.

Eye-related issues, such as glaucoma and cataracts, have also been reported. Regular eye examinations may be advised for patients using budesonide inhalation suspension.

Additionally, increased wheezing immediately following the administration of budesonide inhalation suspension has been observed.

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 risk of localized infections with Candida albicans in the mouth and pharynx. If oropharyngeal candidiasis occurs, it should be treated with appropriate local or systemic antifungal therapy while continuing budesonide inhalation suspension. However, therapy may need to be temporarily interrupted under close medical supervision. Patients are advised to rinse their mouths after each inhalation to help mitigate this risk.

It is crucial to inform patients that budesonide inhalation suspension is not intended for the relief of acute asthma symptoms, and they should not use extra doses for this purpose. Acute symptoms should be managed with an inhaled, short-acting beta 2-agonist, such as albuterol. Patients should be instructed to notify their healthcare professional immediately if they experience decreasing effectiveness of their inhaled beta 2-agonists, an increased need for inhalations, or a significant decrease in lung function as defined by their physician.

Patients should be cautioned against discontinuing budesonide inhalation suspension without consulting their healthcare provider, as symptoms may recur following cessation of therapy. Additionally, hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. Patients should discontinue use and seek medical attention 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 promptly, especially if the child has not had chickenpox or been properly vaccinated.

Patients should be informed about the potential for worsening existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. They should also be made aware that budesonide inhalation suspension may lead to systemic corticosteroid effects, such as hypercorticism and adrenal suppression. Patients transitioning from systemic corticosteroids to budesonide inhalation suspension should taper their systemic corticosteroid dosage slowly to avoid adrenal insufficiency, which has been associated with fatalities.

Patients at increased risk for decreased bone mineral density should be advised that corticosteroid use may further elevate this risk. Pediatric patients receiving orally inhaled corticosteroids, including budesonide, may experience a reduction in growth velocity; therefore, healthcare professionals should monitor the growth of children and adolescents closely.

Long-term use of inhaled corticosteroids may increase the risk of eye problems, such as cataracts or glaucoma, and regular eye examinations should be considered. Patients should be instructed to use budesonide inhalation suspension at regular intervals, specifically twice a day, as its effectiveness relies on consistent use. Maximum benefit may not be observed for 4 to 6 weeks or longer after initiating treatment. If symptoms do not improve or worsen during this period, patients should contact their healthcare professional.

Patients should be advised to rinse their child's mouth with water and have them spit it out after each treatment with budesonide inhalation suspension, avoiding swallowing the water to reduce the risk of developing a fungal infection (thrush) in the mouth. If a child has been on long-term corticosteroids and is having their dose lowered or stopped, they should carry a warning card indicating that they may require corticosteroids during times of stress or in the event of an asthma attack that does not respond to bronchodilator medications.

Healthcare providers may need to monitor the child's blood, breathing, and conduct eye examinations while the child is using budesonide inhalation suspension.

Storage and Handling

Budesonide inhalation suspension is supplied in ampules and should be stored upright at controlled room temperature, specifically between 20°C to 25°C (68°F to 77°F), while being protected from light. The product is available under the National Drug Code (NDC) numbers relevant to its packaging.

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. It is essential that any opened ampule is used promptly to ensure efficacy. To maintain the integrity of the unused ampules, they should be returned to the aluminum foil envelope after opening.

Prior to use, the ampule should be gently shaken using a circular motion. It is crucial to keep this product out of reach of children and to avoid freezing to preserve its effectiveness.

Additional Clinical Information

Patients using budesonide inhalation suspension should be advised to rinse their mouths after each inhalation to minimize potential 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.

Additionally, patients transitioning from systemic corticosteroids, particularly those previously maintained on 20 mg or more per day of prednisone (or its equivalent), may be at increased risk for adrenal insufficiency. Therefore, they should carry a medical identification card indicating the need for supplementary systemic corticosteroids during times of stress or severe asthma attacks.

FDA Insert (PDF)

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

View full prescribing information (PDF)