Budesonide

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. Budesonide inhalation suspension is provided as a mixture of two epimers (22R and 22S). The molecular 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 for inhalation via jet nebulizer and contains the active ingredient budesonide (micronized). The inactive ingredients in budesonide inhalation suspension include citric acid monohydrate, disodium edetate, polysorbate 80, sodium chloride, sodium citrate dihydrate, and water for injection. Three dose strengths are available in single-dose ampules: 0.25 mg, 0.5 mg, and 1 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.

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 dosing can be set at 0.5 mg twice daily or 1 mg once 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, it is advised to increase the total daily dose and/or administer the medication as a divided dose. Once asthma stability is attained, the dosage should be gradually reduced.

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 the primary treatment of status asthmaticus or other acute episodes of asthma that require intensive measures. Additionally, it is contraindicated in patients with a known hypersensitivity to any of the ingredients in the formulation.

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 such situations, as it may lead to deterioration of 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 systemic corticosteroids 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 crucial to monitor patients who have major risk factors for decreased bone mineral content.

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

Patients should 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 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 recommended to monitor patients with major risk factors for decreased bone mineral content, track the growth of pediatric patients, and conduct close monitoring for glaucoma and cataracts throughout the course of treatment.

Side Effects

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

Most common adverse reactions reported 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 advised to rinse their mouths following inhalation.

Serious adverse reactions include hypersensitivity reactions such as anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm. If any of these reactions occur, it is advised to discontinue the use of budesonide inhalation suspension immediately.

Patients may also experience a deterioration of disease and acute asthma episodes; therefore, budesonide inhalation suspension should not be used for the relief of acute bronchospasm. Additionally, there is a risk of impaired adrenal function when transferring patients from systemic corticosteroid therapy to budesonide inhalation suspension, necessitating a gradual tapering of oral steroids.

Immunosuppression is another concern, as there is potential for worsening of infections, including existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is advised in patients with these infections, as a more serious or even fatal course of chickenpox or measles can occur in susceptible individuals.

Long-term administration of budesonide inhalation suspension may lead to hypercorticism and adrenal suppression, particularly at very high dosages or in susceptible individuals. If such changes occur, a gradual reduction of the medication is recommended. Furthermore, there is a noted reduction in bone mineral density with long-term use, and patients with major risk factors for decreased bone mineral content should be monitored closely.

In pediatric patients, growth should be monitored due to potential effects on growth. Close monitoring for glaucoma and cataracts is also warranted.

Paradoxical bronchospasm has been reported; if this occurs, budesonide inhalation suspension should be discontinued, and alternative therapy should be instituted. Additionally, healthcare providers should be alert to eosinophilic conditions, including Churg-Strauss syndrome.

While the potential for acute toxic effects following an overdose of budesonide inhalation suspension is low, excessive doses used for prolonged periods may lead to systemic corticosteroid effects such as hypercorticism or growth suppression.

Drug Interactions

Strong inhibitors of Cytochrome P450 3A4, such as ritonavir, may lead to enhanced systemic effects of corticosteroids. Caution is advised when co-administering these agents due to the potential for increased corticosteroid-related adverse effects. It is recommended to monitor patients closely for signs of corticosteroid overactivity and consider dosage adjustments as necessary based on clinical response.

No interactions with other drugs or laboratory tests have been identified.

Packaging & NDC

The table below lists all NDC Code configurations of Budesonide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

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

Adrenal-axis function was evaluated using an ACTH stimulation test at the study's start and end, revealing no significant adrenal suppression in the budesonide groups compared to placebo. However, individual assessments indicated that 7 patients (6 in the budesonide groups and 1 in the placebo group) experienced a decline from normal to subnormal stimulated cortisol levels by Week 12.

Pneumonia occurred more frequently in patients receiving budesonide inhalation suspension, with 2 cases in the treatment groups compared to none in the placebo group. A dose-dependent effect on growth was observed; infants in the placebo arm grew an average of 3.7 cm over 12 weeks, while those receiving budesonide grew 3.5 cm and 3.1 cm in the 0.5 mg and 1 mg groups, respectively. These findings suggest that budesonide inhalation suspension may lead to systemic effects, 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, influenced by dose and duration of treatment. The long-term implications of this growth reduction on final adult height remain unknown, and the potential for "catch up" growth after discontinuation of treatment has not been adequately studied.

In a separate study of asthmatic children aged 5 to 12 years, those treated with budesonide via a dry powder inhaler at 200 mcg twice daily experienced a 1.1-centimeter reduction in growth compared to placebo after one year. Routine monitoring of growth in pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, is recommended. The potential growth effects of prolonged treatment should be carefully weighed against the clinical benefits and 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 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, healthcare providers should continue to monitor geriatric patients closely, as individual responses to medication can vary. It is essential to consider the overall health status and comorbidities of elderly patients when prescribing budesonide inhalation suspension, ensuring that treatment is tailored to their specific needs.

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. A large population-based prospective cohort epidemiological study indicated no increased risk for congenital malformations from the use of inhaled budesonide in early pregnancy, with the rate of recorded congenital malformations among infants whose mothers used the medication being similar to that of the general population (3.8% vs. 3.5%). Additionally, 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).

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 pregnant rats receiving inhaled doses approximately 2 times the MRHDID. In contrast, doses of budesonide at 0.5 times the MRHDID in pregnant rabbits resulted in fetal loss, decreased fetal weight, and skeletal abnormalities, while similar adverse effects were noted in pregnant rats at doses approximately 5 times the MRHDID. Furthermore, a decrease in prenatal viability and viability in pups at birth and during lactation was observed at doses 0.2 times the MRHDID.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20%, respectively. In women with poorly or moderately controlled asthma, there is an increased risk of 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. While budesonide has not been shown to affect delivery, it may impact the growth and development of offspring, as evidenced by reduced survival and decreased mean body weights at doses less than 0.2 times the MRHDID.

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

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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 possible systemic corticosteroid effects that may arise from excessive dosing over extended periods.

Potential Symptoms

In cases of overdose, patients may experience systemic corticosteroid effects, which can include hypercorticism and growth suppression. These symptoms are particularly relevant when inhaled corticosteroids are administered at high doses for prolonged durations.

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 status. 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

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

In two additional two-year studies involving male Fischer and Sprague-Dawley rats, budesonide did not induce gliomas at an oral dose of 50 mcg/kg. However, a statistically significant increase in the incidence of hepatocellular tumors was noted in male Sprague-Dawley rats at the same dose. The concurrent reference corticosteroids, prednisolone and triamcinolone acetonide, exhibited similar findings in these studies.

A 91-week study in mice revealed no treatment-related carcinogenicity at oral doses up to 200 mcg/kg, which is approximately equivalent to and 0.1 times the MRHDID in adults and children aged 12 months to 8 years on a mcg/m² basis.

Budesonide was evaluated for mutagenicity and clastogenicity in six different test systems, including the Ames Salmonella/microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hepatocyte culture, and was found to be non-mutagenic and non-clastogenic.

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

Postmarketing Experience

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, cases of thrush (candida), a fungal infection affecting the mouth and throat, have been reported. There have been instances of worsening asthma or sudden asthma attacks following administration.

Allergic reactions have also been noted, characterized by skin rash, redness or swelling, severe itching, facial swelling, swelling of the mouth and tongue, difficulty breathing or swallowing, chest pain, and feelings of anxiety.

Further, immune system effects have been observed, leading to an increased risk of infections. Reports of adrenal insufficiency have included symptoms such as tiredness, weakness, nausea, vomiting, and low blood pressure.

Other noted effects include a decrease in bone mineral density, potential for slowed or delayed growth, and eye problems such as glaucoma and cataracts. Increased wheezing immediately after taking budesonide inhalation suspension has also been reported.

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, under close medical supervision, therapy with budesonide inhalation suspension may need to be temporarily interrupted. 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.

Patients should not discontinue therapy with budesonide inhalation suspension without consulting their healthcare provider, as symptoms may recur upon discontinuation. Healthcare professionals 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 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 and to consult their physician immediately if exposed. Patients should also 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 advised that budesonide inhalation suspension may lead to systemic corticosteroid effects, such as hypercorticism and adrenal suppression. It is essential to inform patients that deaths due to adrenal insufficiency have occurred during and after transitioning from systemic corticosteroids. Therefore, patients should 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. Additionally, 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, once or twice daily, 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 the aluminum foil envelope has been opened, the shelf life of the unused ampules is limited to 2 weeks, provided they are kept protected from light and returned to the envelope. Any opened ampule must be used promptly. Prior to use, it is recommended to gently shake the ampule using a circular motion. It is essential to keep this product out of reach of children and to avoid freezing.

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 who have previously been 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. Therefore, it is recommended that these patients carry a medical identification card indicating their 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 Sandoz Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)