Budesonide

Description

Budesonide, USP, is the active ingredient in budesonide inhalation suspension, a corticosteroid chemically designated 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) and has a structural formula that reflects its complex molecular architecture.

Budesonide appears as a white to off-white, tasteless, and odorless powder. It is characterized by its 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, indicating its lipophilic nature.

The budesonide inhalation suspension is a sterile formulation intended for inhalation via jet nebulizer. Each suspension contains micronized budesonide, USP, along with inactive ingredients including citric acid monohydrate, disodium edetate, polysorbate 80, sodium chloride, tri-sodium citrate dihydrate, and water for injection. The product is available in two dose strengths in single-dose vials: 0.25 mg and 0.5 mg per 2 mL vial.

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 bronchodilators administered alone, the starting dose is 0.5 mg once daily or 0.25 mg twice daily. In the case of inhaled corticosteroids, the recommended starting dose is 0.5 mg once daily or 0.25 mg twice daily, with the option to increase to a maximum of 0.5 mg twice daily if necessary. For oral corticosteroids, the initial dose is 0.5 mg 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, the total daily dose may be increased and/or administered as a divided dose. 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 and is not suitable for use with ultrasonic devices. It is important to note that this formulation 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 avoid its use, as this 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. Caution should be exercised to avoid its use in such situations, as it may lead to deterioration of the disease and 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 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 at regular dosages in susceptible individuals. 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 important 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 also be monitored for the development of glaucoma and cataracts, as close observation is warranted in these cases.

Paradoxical bronchospasm has been reported with the use of budesonide inhalation suspension. If this occurs, the medication should be discontinued, and alternative therapy should be instituted.

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.

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 recommended that patients be monitored periodically for signs of adverse effects on the oral cavity and advised 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 crucial to discontinue the use of 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 essential 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 recommended.

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 require careful monitoring of growth, as a dose-dependent effect on growth velocity has been noted, with reductions associated with inhaled corticosteroids.

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 instituted.

Eosinophilic conditions, including Churg-Strauss syndrome, should be considered, and vigilance is advised. Notably, pneumonia was observed more frequently in pediatric patients treated with budesonide inhalation suspension compared to those receiving placebo, highlighting the need for careful assessment in this population.

Drug Interactions

The concomitant use of strong Cytochrome P450 3A4 inhibitors, such as ritonavir, should be approached with caution. Co-administration 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 indicated that adrenal-axis function, assessed via an ACTH stimulation test, did not show evidence of adrenal suppression in those receiving budesonide inhalation suspension compared to placebo.

However, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension, with occurrences in the 0.5 mg, 1 mg, and placebo groups being 2, 1, and 0, respectively. The study also noted a dose-dependent effect on growth; infants in the placebo group experienced an average growth of 3.7 cm over 12 weeks, while those in the budesonide inhalation suspension 0.5 mg and 1 mg groups grew 3.5 cm and 3.1 cm, respectively. These findings suggest that the use of budesonide inhalation suspension in infants aged 6 to 12 months 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 on final adult height remain unknown, and the potential for "catch up" growth following 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 cm reduction in growth compared to those receiving placebo after one year.

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 indicate that there are 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 on the use of budesonide, the active ingredient in budesonide inhalation suspension, in pregnant women have not shown an increased risk of abnormalities when administered during pregnancy. A large population-based prospective cohort epidemiological study indicated no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy. Specifically, the rate of recorded congenital malformations among infants born to mothers reporting the use of inhaled budesonide for asthma in early pregnancy was similar to the general population rate (3.8% vs. 3.5%, respectively). 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, respectively).

In animal reproduction studies, budesonide administered by the subcutaneous route caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). However, these effects were not observed in rats that received inhaled doses approximately 2 times the MRHDID. In a fertility and reproduction study, budesonide caused a decrease in prenatal viability and viability in the pups at birth and during lactation, along with a decrease in maternal body-weight gain at doses 0.2 times the MRHDID. In embryo-fetal development studies, budesonide produced fetal loss, decreased fetal weight, and skeletal abnormalities in pregnant rabbits at doses 0.5 times the MRHDID, and similar adverse fetal effects in pregnant rats at doses approximately 5 times the MRHDID. Conversely, no structural abnormalities or embryocidal effects were seen in another study in pregnant rats at doses approximately 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. The estimated background risk of major birth defects and miscarriage in the indicated populations is unknown. Women with poorly or moderately controlled asthma are at increased risk for several 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.

Lactation

Budesonide inhalation suspension is present in human milk; however, there are no available data on its effects on the breastfed child 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.

Human data indicate that when budesonide is delivered via dry powder inhaler, 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 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

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. This may involve adjusting the dosage of budesonide or transitioning to alternative therapies as necessary, while ensuring that the patient's overall treatment plan is maintained effectively.

Healthcare professionals are advised to provide supportive care and to consider consultation with a specialist if severe symptoms arise or if there are concerns regarding the patient's response to treatment.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. However, non-teratogenic effects were noted, including an absence of impact on fertility and reproductive performance 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. At subcutaneous doses of 20 mcg/kg and above, approximately 0.2 times the maximum recommended human dose, there was a decrease in prenatal viability and viability of pups at birth and during lactation, as well as 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 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, approximately 0.5 and 0.1 times the maximum recommended human dose for 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 for adults and children, nor in female rats at doses up to 50 mcg/kg. In two additional two-year studies with male Fischer and Sprague-Dawley rats, no gliomas were detected at the same 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 this dose. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings in these studies.

In a 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 maximum recommended human dose for 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. There have also been observations of immune system effects, indicating a higher likelihood of infections in patients receiving treatment that may weaken the immune system.

Adrenal insufficiency has been documented, characterized by insufficient production of steroid hormones by the adrenal glands. Additionally, a decrease in bone mineral density has been noted, prompting healthcare providers to consider monitoring bone strength during treatment with budesonide inhalation suspension.

Reports of slowed or delayed growth in pediatric patients have emerged, suggesting the need for growth monitoring by healthcare providers during the course of treatment. Eye-related issues, including glaucoma and cataracts, have also been associated with the use of this medication, leading to recommendations for regular eye examinations.

Increased wheezing immediately following the administration of budesonide inhalation suspension has been reported. The most frequently observed side effects include respiratory infections, viral infections, ear infections, nosebleeds, conjunctivitis, and rash.

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.

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, under close medical supervision, it may be necessary to temporarily interrupt the use of budesonide inhalation suspension. 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-agonist, such as albuterol. Patients should be instructed to notify their healthcare professional immediately if they notice any of the following: a decrease in the effectiveness of inhaled, short-acting beta-agonists; an increased need for inhalations of these medications; or a significant decline in lung function as defined by their physician.

Patients should not discontinue therapy with budesonide inhalation suspension without consulting their healthcare provider, as symptoms may recur following discontinuation. They should also be informed about the potential for hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, and should 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, especially in children who have not had chickenpox or been properly vaccinated, they should consult their physician without delay. Additionally, patients should be informed of the potential for worsening existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex.

Patients should be made aware that budesonide inhalation suspension may lead to systemic corticosteroid effects, such as 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 off systemic corticosteroids slowly when switching to budesonide inhalation suspension.

Patients at increased risk for decreased bone mineral density should be advised that the use of corticosteroids may further elevate this risk. Furthermore, it is important to inform patients 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 developing eye problems, such as cataracts or glaucoma; therefore, regular eye examinations should be considered. Patients should be instructed to use budesonide inhalation suspension at regular intervals, either once or twice daily, 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 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 the dose is being reduced or stopped, a warning card should be carried to indicate that the child may require corticosteroids during times of stress or during 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

The product is supplied in a configuration that includes multiple vials, with specific handling and storage requirements to ensure its integrity and efficacy. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

To maintain product quality, it is essential to store the vials upright and protect them from light exposure. Once an envelope has been opened, the shelf life of the unused vials is limited to 2 weeks, provided they are kept protected from light. After opening the aluminum foil envelope, any unused vials should be returned to the envelope to safeguard them from light.

It is important to use any opened vial promptly, and freezing the product is strictly prohibited to prevent degradation.

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

View full prescribing information (PDF)