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 10^3, indicating its hydrophobic 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 patients utilizing bronchodilators alone, the starting dose is 0.5 mg once daily or 0.25 mg twice daily. Inhaled corticosteroids may be initiated at 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 those requiring oral corticosteroids, the recommended starting 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 the once-daily treatment fail to achieve adequate control of symptoms, it is advised to increase the total daily dose and/or administer the dose in divided intervals. Once asthma stability is attained, a gradual titration downwards of the dose is recommended.

Administration should be conducted via inhalation using compressed air-driven jet nebulizers exclusively; the use of ultrasonic devices is contraindicated. This medication is not intended for injection.

Contraindications

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

Patients requiring primary treatment for status asthmaticus or other acute episodes of asthma where intensive measures are necessary. This is due to the need for immediate and aggressive intervention in such cases.

Additionally, the product is contraindicated in individuals with a known hypersensitivity to any of its ingredients, 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. 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. 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 systemic corticosteroids to minimize this risk.

Hypercorticism and adrenal suppression may occur, particularly with very high dosages or at regular dosages in susceptible individuals. Should these changes occur, 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 with 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 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 they should be 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 important 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 should also be monitored for growth effects, as a dose-dependent effect on growth velocity has been noted, with reductions associated with inhaled corticosteroids.

Patients should be closely monitored for the development of glaucoma and cataracts during treatment. In rare 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 warranted. Notably, pneumonia was observed more frequently in pediatric patients treated with budesonide inhalation suspension compared to those receiving placebo.

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 enhance the risk of adverse reactions associated with corticosteroid therapy.

Monitoring for signs of increased corticosteroid effects is recommended, and dosage adjustments may be necessary based on the clinical response and tolerance of the patient.

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 results indicated no significant adrenal suppression in patients receiving budesonide inhalation suspension compared to placebo.

However, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension than in those receiving placebo. Additionally, a dose-dependent effect on growth was noted; 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 had average growths of 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 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 in growth velocity, including its impact on final adult height, remain unknown. Therefore, the growth of pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, should be monitored routinely, such as through stadiometry. 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 collected from these trials 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, 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 demonstrated an increased risk of abnormalities associated with the use of inhaled budesonide 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.

Animal reproduction studies have shown that budesonide can cause 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. In a fertility and reproduction study, budesonide resulted in decreased prenatal viability and viability of pups at birth and during lactation at doses 0.2 times the MRHDID. Additionally, an embryo-fetal development study in pregnant rabbits indicated fetal loss, decreased fetal weight, and skeletal abnormalities at doses 0.5 times the MRHDID, while similar adverse effects were noted in pregnant rats at doses approximately 5 times the MRHDID. Conversely, no structural abnormalities or embryocidal effects were seen in another study involving pregnant rats at doses approximately 2 times the MRHDID.

In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes, including preeclampsia, 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. However, studies indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy, with the rate of recorded congenital malformations among infants whose mothers used inhaled budesonide during this period being similar to the general population rate (3.8% vs. 3.5%). Furthermore, the incidence of orofacial clefts among infants exposed to inhaled budesonide was comparable to the expected number in the normal population (4 children vs. 3.3).

In summary, while animal studies have shown potential risks associated with budesonide, human data suggest that inhaled budesonide does not significantly increase the risk of congenital malformations. Nonetheless, careful consideration and monitoring are advised for pregnant patients using this medication.

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 of these patients.

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 and consider the overall clinical context when prescribing this medication to patients with hepatic impairment.

Overdosage

In the event of an overdose of budesonide inhalation suspension, the potential for acute toxic effects is considered low. However, it is important for healthcare professionals to remain vigilant regarding the implications of excessive dosing.

Systemic Effects of Prolonged Overdose

Should inhaled corticosteroids be administered at excessive doses over an extended duration, there is a risk of systemic corticosteroid effects. These may include hypercorticism, which is characterized by symptoms such as weight gain, hypertension, and glucose intolerance, as well as growth suppression in pediatric patients.

Recommended Actions

In cases of suspected overdose, it is advisable to monitor the patient closely for any signs of systemic corticosteroid effects. If symptoms of hypercorticism or growth suppression are observed, appropriate management strategies should be implemented. This may involve adjusting the dosage or discontinuing the medication under medical supervision, depending on the severity of the symptoms and the clinical judgment of the healthcare provider.

Overall, while the risk of acute toxicity is low, awareness and proactive management of potential systemic effects are essential in the context of budesonide inhalation suspension overdose.

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 resulted in a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg, which is 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, on a mcg/m² basis, nor 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 oral 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 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

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported following the use of budesonide inhalation suspension. Localized infections with Candida albicans have occurred in the mouth and pharynx in some patients. There have been observations of immune system effects, with an increased likelihood of infections; symptoms may include fever, pain, aches, chills, fatigue, nausea, and vomiting.

Adrenal insufficiency has been reported, characterized by insufficient production of steroid hormones by the adrenal glands. Symptoms associated with adrenal insufficiency include tiredness, weakness, nausea, vomiting, and low blood pressure. Additionally, a decrease in bone mineral density has been noted, prompting healthcare providers to consider monitoring bone strength during treatment with budesonide inhalation suspension.

Concerns regarding slowed or delayed growth in pediatric patients have also been raised, leading healthcare providers to monitor growth during treatment. Eye problems, such as glaucoma and cataracts, have been reported, and eye examinations may be recommended for patients using budesonide inhalation suspension. Furthermore, increased wheezing immediately after administration of budesonide inhalation suspension has been documented.

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, there may be instances where therapy with budesonide inhalation suspension needs to be temporarily interrupted under close medical supervision. Patients are encouraged 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 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 decrease 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. 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 any of these reactions occur.

For patients on immunosuppressant doses of corticosteroids, it is important to warn them to avoid exposure to chickenpox or measles and to seek medical advice promptly if exposure occurs. Patients should also be informed about the potential for worsening of 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. It is essential to inform patients that there have been reports of deaths due to adrenal insufficiency during and after transitioning from systemic corticosteroids. Therefore, patients should be advised to taper slowly from systemic corticosteroids when switching to budesonide inhalation suspension.

Patients at increased risk for decreased bone mineral density should be cautioned 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 developing eye problems, such as cataracts or glaucoma; therefore, regular eye examinations should be considered. Patients should be advised to use budesonide inhalation suspension consistently, either once or twice daily, as its effectiveness is contingent upon regular 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

The product is supplied in vials that must be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. It is essential to protect the vials from light to maintain product integrity.

Once a vial has been opened, it should be used promptly to ensure efficacy. Prior to use, the vial should be gently shaken using a circular motion. Additionally, it is crucial to keep the product out of reach of children and to avoid freezing, as this may compromise the quality of the product.

Additional Clinical Information

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

Patients should be instructed to resume oral corticosteroids in large doses during periods of stress or severe asthma attacks and to seek further guidance from their physicians. A gradual weaning from systemic corticosteroids is recommended after switching to budesonide inhalation suspension. Clinicians should monitor lung function, beta-agonist use, and asthma symptoms closely during this transition. Patients must also be vigilant for signs of adrenal insufficiency, such as fatigue, weakness, nausea, vomiting, and hypotension, and should carry a medical identification card indicating their potential need for supplementary systemic corticosteroids during stressful situations or severe asthma attacks.

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)