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. 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. The inactive ingredients in the suspension include disodium edetate, sodium chloride, sodium citrate dihydrate, citric acid monohydrate, polysorbate 80, and Water for Injection. The product is available in three dose strengths 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 medication is not indicated for the relief of acute bronchospasm.

There are no specific teratogenic or nonteratogenic effects mentioned in the available data.

Dosage and Administration

Healthcare professionals are advised to initiate treatment with the lowest recommended dose based on the patient's previous therapy. For patients who have been using bronchodilators alone, the starting dose is 0.5 mg once daily or 0.25 mg twice daily. For those previously treated with inhaled corticosteroids, the recommended starting dose is also 0.5 mg once daily or 0.25 mg twice daily, with the option to increase to 0.5 mg twice daily if necessary. In patients who have been on oral corticosteroids, the initial dosing can be 0.5 mg twice daily or 1 mg once daily.

In symptomatic children who are not responding to non-steroidal therapy, a starting dose of 0.25 mg once daily may be considered. If a once-daily treatment regimen does not achieve adequate control of symptoms, the total daily dose should be increased and/or administered as a divided dose. Once asthma stability is attained, it is recommended to titrate the dose downwards to the lowest effective dose.

The medication is intended for inhalation use only, administered via compressed air-driven jet nebulizers. It is important to note that this medication is not suitable for injection and should not be used with ultrasonic devices.

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 that necessitate intensive measures should not use this product. Additionally, individuals with a known hypersensitivity to any of the ingredients in budesonide inhalation suspension should avoid its use due to the risk of allergic reactions.

Warnings and Precautions

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur in patients using budesonide inhalation suspension. It is essential to monitor patients periodically for signs of adverse effects on the oral cavity. Patients should be advised to rinse their mouths following inhalation to mitigate this risk.

Budesonide inhalation suspension is not indicated for the relief of acute bronchospasm. Healthcare professionals should be aware of the potential for disease deterioration and acute asthma episodes in patients using this medication.

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 significant concern, as the use of budesonide may exacerbate 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 there is a risk of a more severe 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 recommended 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. Should these changes arise, a gradual reduction of budesonide inhalation suspension is advised.

Long-term administration of budesonide may lead to a reduction in bone mineral density. Therefore, it is crucial to monitor patients with major risk factors for decreased bone mineral content. Additionally, the growth of pediatric patients should be closely monitored during treatment.

Patients should be monitored for the development of glaucoma and cataracts, as these conditions warrant close observation.

Paradoxical bronchospasm has been reported; if this occurs, budesonide inhalation suspension should be discontinued, and alternative therapy should be initiated.

Healthcare professionals should remain vigilant for eosinophilic conditions, including Churg-Strauss syndrome, in patients receiving this treatment.

Budesonide inhalation suspension is intended for inhalation only and should not be swallowed. It must be used exclusively with a jet nebulizer machine connected to an air compressor; the use of ultrasonic nebulizers is contraindicated.

Laboratory tests should include monitoring for decreased bone mineral content in at-risk patients, growth assessment in pediatric patients, and close observation for glaucoma and cataracts.

In the event of hypersensitivity reactions, immediate discontinuation of budesonide inhalation suspension is necessary, and emergency medical help should be sought. Similarly, if paradoxical bronchospasm occurs, the medication should be stopped, and the healthcare provider should be contacted for alternative treatment options.

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, patients may experience a deterioration of disease and acute asthma episodes; therefore, this medication should not be used for the relief of acute bronchospasm.

Immunosuppression is another concern, as there is a potential for worsening of existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is advised when prescribing budesonide inhalation suspension to patients with these infections. Furthermore, susceptible patients may experience a more serious or even fatal course of chickenpox or measles.

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

Long-term administration of budesonide inhalation suspension may lead to a reduction in bone mineral density, necessitating monitoring in patients with major risk factors for decreased bone mineral content. Additionally, the growth of pediatric patients should be closely monitored, as a dose-dependent effect on growth has been noted, with reductions in growth velocity associated with inhaled corticosteroids. The long-term implications of this reduction in growth velocity remain unknown.

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, it is essential to discontinue budesonide inhalation suspension and consider alternative therapies.

Lastly, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension compared to those receiving placebo, highlighting the importance of vigilance in monitoring for this adverse reaction. Eosinophilic conditions, including Churg-Strauss syndrome, should also be considered, and healthcare providers should remain alert to these potential complications.

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 when these agents are used together. No specific dosage adjustments are provided; however, clinicians should consider the potential for increased effects and adjust treatment accordingly based on the patient's clinical response.

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. Patients were randomized to receive either 0.5 mg or 1 mg of budesonide inhalation suspension or placebo once daily.

Adrenal-axis function was evaluated using an ACTH stimulation test at the study's start and end, revealing no significant adrenal suppression in patients receiving budesonide compared to placebo. However, pneumonia was observed more frequently in patients treated with budesonide inhalation suspension than in those receiving placebo.

The study 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 showed average growths of 3.5 cm and 3.1 cm for the 0.5 mg and 1 mg doses, respectively. These findings suggest that the use of budesonide inhalation suspension in infants aged 6 to 12 months may lead to systemic effects, including growth suppression, consistent with other studies on inhaled corticosteroids.

Controlled clinical studies have demonstrated that inhaled corticosteroids can reduce growth velocity in pediatric patients, with an average reduction of approximately one centimeter per year. The long-term implications of this reduction on final adult height remain unknown. Therefore, the growth of pediatric patients receiving inhaled corticosteroids, including budesonide inhalation suspension, should be routinely monitored, 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 indicate that there were no overall differences in safety profiles between elderly patients and their younger counterparts. Furthermore, additional clinical and medical surveillance has not revealed any significant differences in responses to treatment between geriatric patients and younger individuals.

Given the lack of observed differences in safety and efficacy, no specific dosage adjustments are recommended for elderly patients. However, healthcare providers should remain vigilant in monitoring this population for any potential adverse effects, as individual responses may vary. It is essential to consider the overall health status and comorbidities of geriatric patients when prescribing budesonide inhalation suspension.

Pregnancy

There are no adequate well-controlled studies of budesonide inhalation suspension in pregnant women. However, published studies on the use of budesonide, the active ingredient in this formulation, indicate that inhaled budesonide does not increase the risk of abnormalities when administered during pregnancy. A large population-based prospective cohort epidemiological study demonstrated no increased risk for congenital malformations associated with inhaled budesonide during early pregnancy, with rates of recorded congenital malformations being similar to those in the general population (3.8% vs. 3.5%, respectively). Additionally, the incidence of orofacial clefts among infants exposed to inhaled budesonide was comparable to expected rates in the normal population (4 children vs. 3.3, respectively).

In animal reproduction studies, budesonide administered by the subcutaneous route resulted in structural abnormalities, embryocidal effects, and reduced fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). However, these adverse effects were not observed in rats receiving inhaled doses approximately 2 times the MRHDID. In an embryo-fetal development study in pregnant rabbits, budesonide produced fetal loss, decreased fetal weight, and skeletal abnormalities at doses 0.5 times the MRHDID. Similarly, in pregnant rats, adverse fetal effects were noted at doses approximately 5 times the MRHDID, while no structural abnormalities or embryocidal effects were seen at doses approximately 2 times the MRHDID.

Experience with oral corticosteroids suggests that rodents may be more susceptible to structural abnormalities from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20%, respectively. In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes, including preeclampsia, prematurity, low birth weight, and small for gestational age in the neonate. Therefore, pregnant women with asthma should be closely monitored, and medication should be adjusted as necessary to maintain optimal asthma control.

There are no well-controlled human studies investigating the effects of budesonide inhalation suspension during labor and delivery. In a peri-and post-natal development study, budesonide did not affect delivery but did impact the growth and development of offspring, with reduced offspring survival and decreased mean body weights at birth and during lactation observed at doses less than 0.2 times the MRHDID and higher. Given these findings, healthcare professionals should weigh the potential risks and benefits of budesonide inhalation suspension in pregnant patients, particularly those with asthma.

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.

Systemic Effects of Overdosage

In cases where inhaled corticosteroids are administered at excessive doses over an extended duration, systemic corticosteroid effects may manifest. Notable among these effects are hypercorticism and growth suppression.

Recommended Actions

In the event of suspected overdosage, it is advisable to monitor the patient for any signs of systemic corticosteroid effects. Should symptoms arise, 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.

Overall, while the risk of acute toxicity is low, vigilance is warranted to mitigate potential systemic effects associated with prolonged excessive use of budesonide inhalation suspension.

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 the pups at birth and during lactation, alongside a reduction in maternal body-weight gain. No adverse effects were recorded at a dose of 5 mcg/kg, which is approximately 0.05 times the maximum recommended human dose on a mcg/m² basis.

In a two-year study involving Sprague-Dawley rats, budesonide resulted in a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg, approximately 0.5 and 0.1 times the maximum recommended human dose in adults and children aged 12 months to 8 years, respectively, on a mcg/m² basis. No tumorigenicity was observed in male rats at oral doses up to 25 mcg/kg, approximately 0.2 and 0.04 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 with 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 conducted in mice, budesonide did not demonstrate any treatment-related carcinogenicity at oral doses up to 200 mcg/kg, which is approximately equivalent to and 0.1 times the maximum recommended human dose in adults and children aged 12 months to 8 years 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 been observed in the mouth and pharynx in some patients. There have also been reports of immune system effects, which may lead to an increased risk of infections. Symptoms associated with infections can include fever, pain, aches, chills, fatigue, nausea, and vomiting.

Adrenal insufficiency has been noted, characterized by insufficient production of steroid hormones by the adrenal glands. Symptoms of this condition may include tiredness, weakness, nausea, vomiting, and low blood pressure. Additionally, a decrease in bone mineral density has been reported, 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, suggesting that healthcare providers may wish 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 following the 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.

Healthcare providers should counsel patients that the effects of mixing budesonide inhalation suspension with other nebulizable medications have not been adequately studied; therefore, budesonide inhalation suspension should be administered separately in the nebulizer. Patients should also be made aware of the potential for localized infections with Candida albicans in the mouth and pharynx, which have been reported in some individuals.

In the event that oropharyngeal candidiasis develops, patients should be instructed to seek treatment 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 should be advised to rinse their mouth after each 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 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 following discontinuation. Healthcare professionals should inform patients about the potential for hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, and advise them to discontinue budesonide inhalation suspension 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. Additionally, patients should be informed of the potential for worsening of existing 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, including hypercorticism and adrenal suppression. It is important to inform patients that there have been reports of deaths due to adrenal insufficiency 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. 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, either once or twice a day, as its effectiveness is contingent upon consistent use. Maximum therapeutic 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

Budesonide inhalation suspension is supplied in ampules and should be stored upright at a controlled room temperature of 20 to 25°C (68 to 77°F), ensuring protection from light. The product must not be frozen.

Once an envelope has been opened, the shelf life of the unused ampules is limited to 2 weeks, provided they are kept protected from light and returned to the aluminum foil envelope after opening. Any opened ampule should 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.

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

View full prescribing information (PDF)