Budesonide

Description

Budesonide, the active ingredient in budesonide inhalation suspension, is a corticosteroid with the chemical designation of (RS)-11β, 16α, 17, 21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. It exists as a mixture of two epimers, 22R and 22S. The empirical formula of budesonide is C25H34O6, and it has a molecular weight of 430.5. The structural formula is represented as follows:

Budesonide appears as a white to off-white, tasteless, and odorless powder that is practically insoluble in water and 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 10³.

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

The delivery of budesonide to the lungs is influenced by patient-specific factors, the type of jet nebulizer used, and the performance of the compressor. In vitro studies using the Pari-LC-Jet Plus Nebulizer/Pari Master compressor system indicate that the mean delivered dose at the mouthpiece is approximately 17% of the nominal dose at a mean flow rate of 5.5 L/min, with a mean nebulization time of 5 minutes or less. Budesonide inhalation suspension should be administered using jet nebulizers at appropriate flow rates, utilizing either face masks or mouthpieces.

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 recommended starting dose for bronchodilators is 0.5 mg once daily or 0.25 mg twice daily. For inhaled corticosteroids, the initial 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. Oral corticosteroids should be administered at a dose of 0.5 mg twice daily. In symptomatic children who do not respond to non-steroidal therapy, a starting dose of 0.25 mg once daily may be considered.

If once-daily treatment does not achieve adequate control, 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.

The medication is intended for inhalation use only via compressed air-driven jet nebulizers; it is not suitable for use with ultrasonic devices and is not for injection.

Contraindications

Use of budesonide inhalation suspension is contraindicated in patients with hypersensitivity to any of its ingredients. Additionally, it should not be used as the primary treatment for status asthmaticus or other acute episodes of asthma that require intensive measures.

Warnings and Precautions

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur in patients using budesonide inhalation suspension. Healthcare professionals should monitor patients periodically for signs of adverse effects on the oral cavity and advise them to rinse their mouth following inhalation to mitigate this risk.

Budesonide inhalation suspension is not indicated for the relief of acute bronchospasm. Therefore, healthcare providers should be cautious in its use to avoid deterioration of 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. Caution is advised when prescribing budesonide inhalation suspension to these patients, as they may experience a more serious or even fatal course of chickenpox or measles.

When transferring patients from systemic corticosteroids 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, especially with very high dosages or in susceptible individuals. Should these changes be 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 essential 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 these conditions may arise during treatment.

In the event of paradoxical bronchospasm, the use of budesonide inhalation suspension 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 present during treatment.

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

Side Effects

patients receiving budesonide inhalation suspension, particularly at higher doses or with prolonged use. Monitor for signs of adrenal insufficiency and consider dose adjustments as necessary.

The most common adverse reactions observed in clinical trials, occurring in more than 3% of participants, include respiratory infections, rhinitis, coughing, otitis media, viral infections, moniliasis, gastroenteritis, vomiting, diarrhea, abdominal pain, ear infections, epistaxis, conjunctivitis, and rash.

In clinical trials, the incidence of respiratory infections was reported at 36% for the vehicle placebo group, with rates of 34%, 35%, and 38% for the 0.25 mg, 0.5 mg, and 1 mg doses, respectively. Rhinitis was observed in 9% of the vehicle placebo group, with incidences of 7%, 11%, and 12% for the respective doses. Coughing occurred in 5% of the vehicle placebo group, with rates of 5%, 9%, and 8% for the 0.25 mg, 0.5 mg, and 1 mg doses.

Other notable adverse reactions include otitis media, which was reported in 11% of the vehicle placebo group and 12%, 11%, and 9% for the respective doses. Viral infections were noted in 3% of the vehicle placebo group, with rates of 4%, 5%, and 3% for the 0.25 mg, 0.5 mg, and 1 mg doses. Moniliasis was reported in 2% of the vehicle placebo group, with incidences of 4%, 3%, and 4% for the respective doses.

Gastrointestinal disorders such as gastroenteritis occurred in 4% of the vehicle placebo group, with similar rates across the doses. Vomiting was reported in 3% of the vehicle placebo group, with rates of 2%, 4%, and 4% for the respective doses. Diarrhea and abdominal pain were also reported, with varying incidences across the treatment groups.

Additional adverse reactions noted in clinical experience include cervical lymphadenopathy, earache, fatigue, flu-like disorders, allergic reactions, eye infections, herpes simplex, external ear infections, fractures, anorexia, myalgia, hyperkinesia, emotional lability, chest pain, dysphonia, stridor, contact dermatitis, eczema, pustular rash, pruritus, and purpura.

Patients should be monitored for localized infections, particularly Candida albicans infections of the mouth and throat, and advised to rinse their mouths following inhalation. Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported; discontinuation of budesonide inhalation suspension is recommended if such reactions occur. Caution is advised in patients with existing infections, as immunosuppression may lead to a worsening of these conditions.

Drug Interactions

The concomitant use of strong cytochrome P450 3A4 inhibitors, such as ritonavir, should be approached with caution. This combination may lead to an increase in systemic corticosteroid effects, which could heighten the risk of adverse reactions associated with corticosteroid therapy.

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

Packaging & NDC

The table below lists all NDC Code configurations of Budesonide, 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 mean changes from baseline indicated no adrenal suppression in patients receiving budesonide inhalation suspension compared to placebo; however, 7 patients (6 in the treatment arms and 1 in the placebo arm) experienced a shift from normal to subnormal stimulated cortisol levels by Week 12.

Pneumonia occurred more frequently in patients treated with budesonide inhalation suspension, with 2 cases in the 0.5 mg group, 1 in the 1 mg group, and none in the placebo group. A dose-dependent effect on growth was observed, with infants in the placebo arm experiencing an average growth of 3.7 cm over 12 weeks, compared to 3.5 cm and 3.1 cm in the 0.5 mg and 1 mg budesonide 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 exposure. The long-term implications of this 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 at 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 the 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 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 have not demonstrated an increased risk of abnormalities associated with the use of inhaled budesonide during pregnancy. In animal reproduction studies, budesonide has been shown to cause structural abnormalities, embryocidal effects, and reduced fetal weights in rats and rabbits at doses below the maximum recommended human daily inhalation dose (MRHDID). Notably, these adverse effects were not observed in rats receiving inhaled doses approximately two 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. A large population-based prospective cohort study indicated no increased risk for congenital malformations associated with the use of inhaled budesonide during early pregnancy. The rate of recorded congenital malformations among infants whose mothers used inhaled budesonide during early pregnancy was comparable to the general population rate (3.8% vs. 3.5%). Additionally, the incidence of orofacial clefts among infants exposed to inhaled budesonide was similar to the expected number in the normal population (4 children vs. 3.3).

In fertility and reproduction studies, budesonide caused a decrease in prenatal viability and viability in pups at birth and during lactation at doses 0.2 times the MRHDID. In an embryo-fetal development study in pregnant rabbits, budesonide resulted in fetal loss, decreased fetal weight, and skeletal abnormalities at doses 0.5 times the MRHDID. Conversely, another embryo-fetal development study in pregnant rats did not reveal structural abnormalities or embryocidal effects at doses approximately two 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 available 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 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. It is advisable to consult relevant clinical guidelines and consider the patient's overall health status when determining the course of action.

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 intake 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. In a separate 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 MRHDID.

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. The results indicated that budesonide was neither mutagenic nor clastogenic.

Fertility and reproductive performance were unaffected in rats administered subcutaneous doses of budesonide 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 0.04 times the MRHDID in adults on a mcg/m² basis.

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, with an increased likelihood of infections noted in patients receiving treatment. Symptoms of infection may include fever, pain, aches, chills, fatigue, nausea, and vomiting.

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

Additionally, a decrease in bone mineral density has been observed, prompting healthcare providers to consider monitoring bone strength during treatment with budesonide inhalation suspension. Reports of slowed or delayed growth in pediatric patients have also been noted, leading to recommendations for growth monitoring by healthcare providers.

Eye-related issues, such as glaucoma and cataracts, have been documented, and healthcare providers may suggest regular eye examinations for patients using budesonide inhalation suspension. Furthermore, instances of increased wheezing immediately following the administration of budesonide inhalation suspension have 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.

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 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 must be instructed to notify their healthcare professional immediately if they experience any of the following: a decrease in the effectiveness of inhaled, short-acting beta-agonists; an increased need for inhalations of inhaled, short-acting beta-agonists; 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 upon discontinuation.

Healthcare providers should inform patients about the risk of hypersensitivity reactions, which may include anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm. If any of these reactions occur, patients should discontinue the use of budesonide inhalation suspension.

Patients receiving immunosuppressant doses of corticosteroids should be cautioned to avoid exposure to chickenpox or measles. If exposure occurs, they should consult their physician promptly. 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 advised that budesonide inhalation suspension may lead to systemic corticosteroid effects, such as 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 off systemic corticosteroids slowly when switching to budesonide inhalation suspension.

Patients at increased risk for decreased bone mineral density should be made aware that the use of corticosteroids may further elevate this risk. Furthermore, patients should be informed that orally inhaled corticosteroids, including budesonide, 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 and glaucoma; therefore, regular eye examinations should be considered. Patients should be instructed 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 advised 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°C to 25°C (68°F 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 essential to gently shake the ampule using a circular motion.

This product should be kept out of reach of children to ensure safety.

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 Rising Pharma Holdings, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)