Budesonide Inhalation

Description

Budesonide, the active component of budesonide inhalation suspension, is a corticosteroid designated chemically as (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 its molecular weight is 430.5 g/mol. Budesonide appears as a white to off-white, tasteless, odorless powder that is practically insoluble in water and in heptane, sparingly soluble in ethanol, and freely soluble in chloroform. Its partition coefficient between octanol and water at pH 7.4 is 1.6 x 10^3.

Budesonide inhalation suspension is a sterile suspension intended for inhalation via jet nebulizer, containing micronized budesonide as the active ingredient. Inactive ingredients include sodium chloride, disodium edetate, polysorbate 80, citric acid, tri sodium citrate, and water for injection. The product is available in two dose strengths in single-dose ampules: 0.25 mg and 0.5 mg per 2 mL ampule.

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.

Limitations of Use: This drug is not indicated for the relief of acute bronchospasm.

Dosage and Administration

The recommended dosing for the medication is based on the patient's previous therapy. For patients who have been using bronchodilators alone, the recommended dose is 0.25 mg administered twice daily. For those who have been treated with inhaled corticosteroids, the initial dose is 0.25 mg twice daily, which may be increased to a maximum of 0.5 mg twice daily if necessary. In patients previously on oral corticosteroids, the recommended dose is 0.5 mg twice daily.

Once asthma stability is achieved, it is advised to titrate the dose downwards to the lowest effective dose.

This medication is intended for inhalation use only via compressed air-driven jet nebulizers. It is important to note that this medication is not suitable for use with ultrasonic devices and is not 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 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. Caution should be exercised to avoid its use in such situations, as it may lead to deterioration of the disease or acute asthma episodes.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. Should any of these reactions occur, the use of budesonide inhalation suspension 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 infections like chickenpox or measles in susceptible individuals.

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 at standard 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 recommended 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 with the use of budesonide inhalation suspension. If this reaction is observed, the medication 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.

To ensure patient safety, it is crucial to monitor the aforementioned parameters, including bone mineral density in at-risk patients, growth in pediatric patients, and the potential development of glaucoma and cataracts.

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 require monitoring and management.

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, there is a potential for immunosuppression, which may lead to a worsening of 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 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. Furthermore, hypercorticism and adrenal suppression may occur, particularly with very high dosages or in susceptible individuals. If such changes are observed, a gradual reduction of budesonide inhalation suspension is warranted.

Long-term administration of budesonide inhalation suspension may lead to a reduction in bone mineral density; therefore, patients with major risk factors for decreased bone mineral content should be monitored closely. Pediatric patients should also be monitored for growth effects, as a dose-dependent effect on growth velocity has been noted with inhaled corticosteroids.

Patients should be closely monitored for the development of glaucoma and cataracts during treatment. In some cases, paradoxical bronchospasm may occur; if this happens, budesonide inhalation suspension should be discontinued, and alternative therapy should be initiated.

Eosinophilic conditions, including Churg-Strauss syndrome, should be considered, and vigilance is advised. Additionally, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension compared to those receiving placebo, highlighting the need for careful patient assessment and monitoring throughout the course of 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.

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 Inhalation (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 indicated a dose-dependent effect on growth. Infants in the placebo group experienced an average growth of 3.7 cm over 12 weeks, while those receiving budesonide inhalation suspension at doses of 0.5 mg and 1 mg had average growths of 3.5 cm and 3.1 cm, respectively. These findings suggest that the use of budesonide inhalation suspension in infants may lead to systemic effects, consistent with growth suppression observed in other studies involving inhaled corticosteroids.

Controlled clinical studies have demonstrated that inhaled corticosteroids can reduce growth velocity in pediatric patients, with an average reduction of approximately one centimeter per year (ranging from 0.3 to 1.8 cm per year). The long-term implications of this reduction in growth velocity, including its effect on final adult height, remain unknown. Additionally, the potential for "catch up" growth following the discontinuation of treatment with inhaled corticosteroids 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 at a dose of 200 mcg twice daily experienced a 1.1-centimeter reduction in growth compared to those receiving placebo after one year. Therefore, routine monitoring of growth in pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, is recommended, utilizing methods such as stadiometry. To minimize systemic effects, it is advised that each patient 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 collected from these trials 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, it is prudent for healthcare providers to monitor geriatric patients closely, as individual responses to medication can vary. Caution should be exercised when prescribing to this population, particularly in the context of polypharmacy or the presence of comorbid conditions that may affect treatment outcomes.

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. The estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies 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.

Animal reproduction studies have demonstrated that budesonide can cause structural abnormalities, is embryocidal, and reduces fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). Specifically, 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, adverse fetal effects were observed at doses approximately 5 times the MRHDID, while no structural abnormalities or embryocidal effects were seen at doses approximately 2 times the MRHDID. Additionally, a fertility and reproduction study indicated a decrease in prenatal viability and viability in the pups at birth and during lactation at doses 0.2 times the MRHDID.

Despite these findings in animal studies, studies of pregnant women indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy. The rate of recorded congenital malformations among infants whose mothers were exposed to inhaled budesonide during early pregnancy was similar to the general population rate (3.8% vs. 3.5%). Furthermore, 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).

There are no well-controlled human studies that have investigated the effects of budesonide inhalation suspension during labor and delivery. Given the potential risks associated with poorly controlled asthma and the findings from animal studies, healthcare professionals should weigh the benefits of asthma control against the potential risks when considering the use of budesonide 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 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 indicate 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 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 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 systemic effects that may arise from the excessive use of inhaled corticosteroids over extended periods.

Potential Symptoms

In cases of prolonged excessive dosing, patients may experience systemic corticosteroid effects, which can include hypercorticism and growth suppression. These symptoms are indicative of the body's response to elevated corticosteroid levels and warrant careful monitoring.

Recommended Actions

In the event of suspected overdose, it is advisable to assess the patient's clinical status and consider the need for supportive care. While acute toxicity is unlikely, ongoing evaluation for signs of hypercorticism or growth suppression is essential, particularly in pediatric patients.

Healthcare professionals should provide guidance on the appropriate use of budesonide inhalation suspension to mitigate the risk of overdose and its associated complications.

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 on a mcg/m² basis, 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 recorded at a dose of 5 mcg/kg, approximately 0.05 times the maximum recommended human dose on a mcg/m² basis.

In a two-year study involving 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 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 0.04 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. In two additional two-year studies conducted in 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 oral dose. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings in these studies.

In a 91-week study involving 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 on a mcg/m² basis. 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

Postmarketing experience has identified several adverse events associated with the use of budesonide inhalation suspension, reported voluntarily or through surveillance programs.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been documented. Additionally, there is an association with immune system effects, leading to an increased risk of infections. Symptoms indicative of infections may include fever, pain, aches, chills, fatigue, nausea, and vomiting.

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

Further observations include a decrease in bone mineral density, prompting healthcare providers to consider monitoring this parameter during treatment. There have been reports of slowed or delayed growth, necessitating regular growth assessments by healthcare providers.

Eye-related issues, such as glaucoma and cataracts, have been noted, with recommendations for eye examinations during treatment. Lastly, instances of increased wheezing immediately following the administration of budesonide inhalation suspension have been recorded.

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, utilizing 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.

Healthcare providers should discuss with patients that the effects of mixing budesonide inhalation suspension with other nebulizable medications have not been adequately assessed; therefore, budesonide inhalation suspension should be administered separately in the nebulizer.

Patients should be made aware of the potential for localized infections with Candida albicans in the mouth and pharynx. If 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. Rinsing the mouth after inhalation is strongly advised.

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 beta2-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 beta2-agonists; an increased need for inhalations of inhaled, short-acting beta2-agonists; or a significant decrease in lung function as outlined by their physician. Additionally, patients should not discontinue therapy with budesonide inhalation suspension without consulting their healthcare provider, as symptoms may recur upon discontinuation.

Healthcare providers should inform patients about the risk of hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, which have been reported with the use of budesonide inhalation suspension. Patients should discontinue use and seek medical attention if such reactions occur.

Patients on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and to consult their physician immediately if exposed. It is also important to inform patients of the potential for worsening existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

Patients should be advised that budesonide inhalation suspension may lead to systemic corticosteroid effects, including hypercorticism and adrenal suppression. They should be informed that deaths due to adrenal insufficiency have occurred during and after transitioning from systemic corticosteroids, and therefore, patients should taper slowly from systemic corticosteroids when switching to budesonide inhalation suspension.

For patients at increased risk for decreased bone mineral density, it should be emphasized that the use of corticosteroids may pose an additional 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, specifically twice a day, as its effectiveness relies on consistent use. Maximum benefit may not be achieved 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 temperature range of 20° to 25°C (68° to 77°F), ensuring protection from light. Once an envelope has been opened, the shelf life of the unused ampules is limited to 2 weeks, provided they are kept protected. It is essential to return any unused ampules to the aluminum foil envelope after opening to maintain their protection from light. Opened ampules must be used promptly, and prior to use, each ampule should be gently shaken in a circular motion. Freezing of the product is not permitted.

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, it is recommended that these patients 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 Inhalation as submitted by Amneal Pharmaceuticals of New York LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)