Pulmicort

Description

Budesonide, the active component of PULMICORT FLEXHALER, is 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). 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, 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 10^3.

PULMICORT FLEXHALER is an inhalation-driven multi-dose dry powder inhaler that contains a formulation of 1 mg per actuation of micronized budesonide and micronized lactose monohydrate, which includes trace levels of milk proteins. Each actuation of PULMICORT FLEXHALER 180 mcg delivers 160 mcg of budesonide from the mouthpiece, while each actuation of PULMICORT FLEXHALER 90 mcg delivers 80 mcg of budesonide from the mouthpiece.

Uses and Indications

PULMICORT FLEXHALER is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients six years of age or older.

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

For oral inhalation only.

In patients 18 years of age and older, the recommended starting dosage is 360 mcg administered twice daily. In certain adult patients, a starting dose of 180 mcg twice daily may be sufficient. The maximum dosage should not exceed 720 mcg administered twice daily.

For patients aged 6 to 17 years, the recommended starting dosage is 180 mcg administered twice daily. In some pediatric patients, a starting dose of 360 mcg twice daily may be appropriate. The maximum dosage for this age group should not exceed 360 mcg administered twice daily.

Healthcare professionals should ensure that patients are instructed on the proper inhalation technique to achieve optimal drug delivery.

Contraindications

Use of PULMICORT FLEXHALER is contraindicated in the following situations:

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

Additionally, PULMICORT FLEXHALER is contraindicated in individuals with severe hypersensitivity to milk proteins or any of its ingredients, as this may lead to serious allergic reactions.

Warnings and Precautions

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur in patients using PULMICORT FLEXHALER. 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.

PULMICORT FLEXHALER is not indicated for the relief of acute asthma symptoms. In cases of rapidly deteriorating asthma, patients require immediate re-evaluation to ensure appropriate management.

Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported with the use of PULMICORT FLEXHALER. Should any of these reactions occur, the medication must be discontinued immediately.

Immunosuppression may occur with PULMICORT FLEXHALER, potentially exacerbating existing infections such as 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 fatal course of chickenpox or measles in susceptible individuals.

When transferring patients from systemic corticosteroid therapy to PULMICORT FLEXHALER, there is a risk of impaired adrenal function. It is essential to taper patients slowly from oral steroids to minimize this risk.

Hypercorticism and adrenal suppression may occur, particularly with very high dosages or in susceptible individuals at standard dosages. If such changes are observed, a gradual reduction of PULMICORT FLEXHALER should be implemented.

Long-term administration of PULMICORT FLEXHALER 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 PULMICORT FLEXHALER to ensure normal development.

Patients should be monitored for the development of glaucoma and cataracts, as these conditions may arise during treatment.

Paradoxical bronchospasm has been reported; if this occurs, PULMICORT FLEXHALER should be discontinued, and alternative therapy should be initiated.

Healthcare professionals should remain vigilant for eosinophilic conditions and Churg-Strauss syndrome in patients receiving PULMICORT FLEXHALER.

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

Most common adverse reactions observed in patients using PULMICORT FLEXHALER include nasopharyngitis, nasal congestion, pharyngitis, allergic rhinitis, viral upper respiratory tract infections, nausea, viral gastroenteritis, otitis media, and oral candidiasis.

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 mouth following inhalation to mitigate this risk.

Patients should be cautioned that PULMICORT FLEXHALER is not intended for the relief of acute asthma symptoms. In cases of rapidly deteriorating asthma, immediate re-evaluation is necessary. Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. If any of these reactions occur, discontinuation of PULMICORT FLEXHALER is advised.

Immunosuppression may occur, leading to a potential worsening of infections, including existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. Caution is warranted when prescribing to patients with these infections. Additionally, susceptible patients may experience a more serious or even fatal course of chickenpox or measles.

When transferring patients from systemic corticosteroid therapy to PULMICORT FLEXHALER, there is a risk of impaired adrenal function. It is essential to taper patients slowly from oral steroids to minimize this risk. Hypercorticism and adrenal suppression may occur, particularly with very high dosages or at regular dosages in susceptible individuals. If such changes are observed, a gradual reduction of PULMICORT FLEXHALER is recommended.

Long-term administration of PULMICORT FLEXHALER may lead to a reduction in bone mineral density; therefore, patients with major risk factors for decreased bone mineral content should be monitored. Pediatric patients should have their growth closely monitored during treatment.

Patients should also be aware of the potential for glaucoma and cataracts, necessitating close monitoring. In rare cases, paradoxical bronchospasm may occur; if this happens, PULMICORT FLEXHALER should be discontinued, and alternative therapy should be initiated.

Eosinophilic conditions, including Churg-Strauss syndrome, should be considered, and vigilance is advised.

While the potential for acute toxic effects following an overdose of PULMICORT FLEXHALER is low, excessive doses (up to 6400 mcg daily) used for prolonged periods may lead to systemic corticosteroid effects such as hypercorticism. Postmarketing experience indicates that acute overdose of inhaled budesonide commonly remains asymptomatic.

Drug Interactions

Co-administration of strong Cytochrome P450 3A4 inhibitors, such as ritonavir, should be approached with caution. The use of these inhibitors may lead to an increase in systemic corticosteroid effects, which could necessitate careful monitoring of the patient's response and potential side effects.

Currently, there is no information available regarding interactions with other drugs or laboratory tests. Therefore, healthcare professionals should remain vigilant for any unexpected clinical effects when these agents are used concurrently.

Packaging & NDC

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

Pediatric Use

In a 12-week pivotal study involving 204 patients aged 6 to 17 years, PULMICORT FLEXHALER was administered twice daily, demonstrating efficacy comparable to that observed in patients aged 18 years and older. The type and frequency of adverse events reported in this pediatric population were similar to those in older patients. However, the safety and effectiveness of PULMICORT FLEXHALER in asthma patients under 6 years of age have not been established.

Controlled clinical studies indicate that orally inhaled corticosteroids, including budesonide, may lead to a reduction in growth velocity in pediatric patients. This reduction has been noted even in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting that growth velocity may serve as a more sensitive indicator of systemic corticosteroid exposure than some HPA-axis function tests. The long-term implications of this growth reduction, including its impact on final adult height, remain unknown, and the potential for "catch up" growth following discontinuation of treatment has not been adequately studied.

In a study involving asthmatic children aged 5 to 12 years, those treated with a different PULMICORT dry powder inhaler at a dose of 200 mcg twice daily experienced a 1.1-centimeter reduction in growth compared to those receiving placebo at the end of one year. Notably, this difference did not increase over three additional years of treatment, and by the end of four years, growth velocities were similar between the treatment and placebo groups. However, conclusions from this study may be confounded by the unequal use of corticosteroids among treatment groups and the inclusion of patients who entered puberty during the study.

The administration of inhaled budesonide via a different PULMICORT dry powder inhaler at doses up to 800 mcg/day (mean daily dose 445 mcg/day) or via a pressurized metered-dose inhaler at doses up to 1200 mcg/day (mean daily dose 620 mcg/day) to 216 pediatric patients aged 3 to 11 years over 2 to 6 years showed no significant effect on statural growth compared to 62 matched control patients not receiving corticosteroids. Nonetheless, the long-term effects of inhaled budesonide on growth are not fully understood.

Monitoring of growth in pediatric patients receiving orally inhaled corticosteroids, including PULMICORT FLEXHALER, is recommended (e.g., via stadiometry). If growth suppression is observed in a child or adolescent on corticosteroids, it is important to consider their potential sensitivity to this effect. The benefits of prolonged treatment should be carefully weighed against the potential growth effects, and each patient should be titrated to the lowest effective dose to minimize systemic effects.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, were represented in controlled clinical studies of inhaled budesonide, with a total of 153 patients in this age group, including 11 treated with PULMICORT FLEXHALER. Among these, one patient was 75 years of age or older.

No overall differences in safety were observed between elderly patients and their younger counterparts. However, the clinical studies did not include a sufficient number of patients aged 65 years and over to adequately assess differences in efficacy between these groups. Additionally, other clinical or medical surveillance experiences have not identified any significant differences in responses between elderly and younger patients.

In general, when prescribing for elderly patients, dose selection should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Regular monitoring and assessment of the patient's response to treatment are recommended to ensure safety and efficacy.

Pregnancy

There are no adequate well-controlled studies of PULMICORT FLEXHALER in pregnant women. However, published studies on the use of budesonide, the active ingredient in PULMICORT FLEXHALER, indicate that inhaled budesonide does not increase the risk of abnormalities when administered during pregnancy. A large population-based prospective cohort epidemiological study found 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 the expected number in the normal population (4 children vs. 3.3, respectively).

Animal reproduction studies have shown that budesonide, when administered subcutaneously, caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at doses less than the maximum recommended human daily inhalation dose (MRHDID). However, these adverse effects were not observed in rats receiving inhaled doses approximately 2 times the MRHDID. Budesonide has been associated with decreased prenatal viability and viability in pups at birth and during lactation, as well as decreased maternal body-weight gain at doses 0.1 times the MRHDID. In pregnant rabbits, doses of 0.3 times the MRHDID resulted in fetal loss, decreased fetal weight, and skeletal abnormalities, while similar adverse fetal effects were noted in pregnant rats at doses approximately 4 times the MRHDID. Notably, no structural abnormalities or embryocidal effects were seen in another embryo-fetal development study in pregnant rats at doses approximately 2 times the MRHDID.

The estimated background risk of major birth defects and miscarriage in the U.S. general population is 2% to 4% and 15% to 20%, respectively. 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 PULMICORT FLEXHALER during labor and delivery. Given the potential risks associated with poorly controlled asthma during pregnancy, healthcare professionals should weigh the benefits of asthma control against any potential risks when considering the use of PULMICORT FLEXHALER in pregnant patients.

Lactation

Budesonide has been shown to affect prenatal viability and the viability of pups at birth and during lactation in animal studies. Specifically, at doses of 0.1 times the maximum recommended human dose (MRHDID) on a mcg/m² basis (maternal subcutaneous doses of 20 mcg/kg/day and above), there was a noted decrease in maternal body-weight gain.

In a peri-and post-natal development study involving rats, budesonide did not impact delivery; however, it did affect the growth and development of the offspring. At doses of 0.1 times the MRHDID and higher, there was a reduction in offspring survival, and surviving offspring exhibited decreased mean body weights at birth and during lactation. These adverse effects were observed in conjunction with maternal toxicity.

Given these findings, healthcare professionals should exercise caution when considering the use of budesonide in lactating mothers, as the potential effects on breastfed infants and the overall impact on lactation are not fully established.

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

Acute overdose of PULMICORT FLEXHALER is generally associated with a low potential for toxic effects. However, it is important to note that the administration of excessive doses over extended periods may lead to systemic corticosteroid effects, particularly hypercorticism.

Postmarketing surveillance has shown that instances of acute overdose involving inhaled budesonide frequently present as asymptomatic. This suggests that many patients may not exhibit overt signs of toxicity even when dosages exceed recommended levels.

In cases where excessive doses are administered, particularly those reaching up to 6400 mcg daily over prolonged durations, healthcare professionals should be vigilant for the development of systemic corticosteroid effects, including hypercorticism. Monitoring and management of these potential effects are essential to ensure patient safety and mitigate any adverse outcomes associated with prolonged corticosteroid exposure.

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 0.5 times the maximum recommended human daily inhalation dose (MRHDID) in adults on a mcg/m² basis. However, at a subcutaneous dose of 20 mcg/kg/day, approximately 0.1 times the MRHDID in adults on a mcg/m² basis, decreases in maternal body weight gain, prenatal viability, and the viability of the young at birth and during lactation were noted. No such adverse effects were recorded at a dose of 5 mcg/kg, approximately 0.03 times the MRHDID in adults on a mcg/m² basis.

In a 104-week oral study involving Sprague-Dawley rats, a statistically significant increase in the incidence of gliomas was noted in male rats receiving an oral dose of 50 mcg/kg/day, approximately 0.3 times the MRHDID in adults and children aged 6 to 17 years on a mcg/m² basis. No tumorigenicity was observed in male rats at oral doses up to 25 mcg/kg, approximately 0.2 times the MRHDID, and in female rats at doses up to 50 mcg/kg, approximately 0.3 times the MRHDID. 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 observed in male Sprague-Dawley rats at the same dose. The concurrent reference corticosteroids, prednisone and triamcinolone acetonide, exhibited similar findings in these studies.

There was no evidence of a carcinogenic effect when budesonide was administered orally for 91 weeks to mice at doses up to 200 mcg/kg/day, approximately 0.7 times the MRHDID in adults and children aged 6 to 17 years on a mcg/m² basis. Additionally, 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 PULMICORT FLEXHALER. Additionally, there have been observations of immune system effects, with an increased likelihood of infections associated with medications that may weaken the immune system.

Cases of adrenal insufficiency have been documented, characterized by symptoms such as tiredness, weakness, nausea, vomiting, and low blood pressure. There is also a noted decrease in bone mineral density, warranting regular monitoring by healthcare providers during treatment with PULMICORT FLEXHALER.

Reports indicate potential growth-related issues in children, necessitating regular assessments of growth while using this medication. Furthermore, eye problems, including glaucoma and cataracts, have been identified, highlighting the importance of routine eye examinations during treatment.

Increased wheezing immediately after administration of PULMICORT FLEXHALER has been reported, emphasizing the need for patients to have a short-acting beta2-agonist (rescue inhaler) available to manage sudden wheezing episodes.

Patient Counseling

Patients being treated with PULMICORT FLEXHALER should receive comprehensive information and instructions to ensure the safe and effective use of the medication. It is essential for patients to read and follow the accompanying FDA Approved Patient Labeling to achieve maximum improvement.

Patients should be advised that localized infections with Candida albicans may occur in the mouth and pharynx. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic antifungal therapy while continuing therapy with PULMICORT FLEXHALER. However, therapy may need to be temporarily interrupted under close medical supervision. Rinsing the mouth after inhalation is recommended to minimize this risk.

It is important to inform patients that PULMICORT FLEXHALER 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, which the physician should provide along with instructions for its use.

Patients should be instructed to notify their physician immediately if they experience any of the following: decreasing effectiveness of inhaled, short-acting beta2-agonists; an increased need for inhalations of these medications; or a significant decrease in lung function as outlined by the physician. Patients must not discontinue therapy with PULMICORT FLEXHALER without consulting their healthcare provider, as symptoms may recur upon discontinuation.

Healthcare providers should inform patients about the potential for hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, which have been reported with the use of PULMICORT FLEXHALER. Patients should discontinue the medication if such reactions occur.

Patients should be made aware that PULMICORT FLEXHALER contains small amounts of lactose, which may contain trace levels of milk proteins. This could potentially lead to cough, wheezing, or bronchospasm in patients with a severe milk protein allergy.

For patients on immunosuppressant doses of corticosteroids, it is crucial to warn them to avoid exposure to chickenpox or measles and to consult their physician immediately if exposed. Additionally, patients should be informed about the potential worsening of existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

Patients should be advised that PULMICORT FLEXHALER may cause systemic corticosteroid effects, such as hypercorticism and adrenal suppression. They should be informed that deaths due to adrenal insufficiency have occurred during and after transitioning from systemic corticosteroids. A gradual tapering from systemic corticosteroids is recommended when switching to PULMICORT FLEXHALER.

Patients at increased risk for decreased bone mineral density (BMD) should be cautioned that the use of corticosteroids may pose an additional risk. Furthermore, patients should be informed that orally inhaled corticosteroids, including budesonide inhalation powder, may reduce growth velocity in pediatric patients, necessitating close monitoring of growth in children and adolescents.

Long-term use of inhaled corticosteroids may increase the risk of eye problems, such as cataracts or glaucoma; therefore, regular eye examinations should be considered. Patients should be advised to use PULMICORT FLEXHALER at regular intervals, as its effectiveness depends on consistent use. Maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment. If symptoms do not improve or worsen during this period, patients should contact their physician.

Patients must be carefully instructed on the proper use of PULMICORT FLEXHALER to ensure optimal dose delivery. They may not sense the medication entering their lungs during inhalation, but this does not indicate that the medication was not delivered. Patients should not repeat their inhalation if they do not feel the medication.

It is important to note that this medication is intended for oral inhalation only. Patients should read the Patient Information that accompanies PULMICORT FLEXHALER before starting treatment and each time they receive a refill, as there may be new information. This leaflet does not replace discussions with healthcare providers regarding medical conditions or treatments.

Patients should use PULMICORT FLEXHALER exactly as prescribed by their healthcare provider and must use it regularly for it to be effective. After each dose, patients should rinse their mouth with water and spit it out to reduce the risk of developing a fungal infection in the mouth.

If a dose is missed, patients should take their next regularly scheduled dose when it is due and should not use PULMICORT FLEXHALER more frequently or in greater amounts than prescribed. Patients should always have a short-acting beta2-agonist available for use in case of breathing problems between doses of PULMICORT FLEXHALER or during a sudden asthma attack. They should contact their healthcare provider immediately if their short-acting rescue medication does not relieve asthma symptoms, if they need to use it more frequently than usual, or if their breathing problems worsen while using PULMICORT FLEXHALER.

For patients who have been on corticosteroid medications for an extended period and are now reducing or stopping their dose, carrying a medical alert card is advisable. This card should indicate that they may require increased corticosteroids during times of stress or in the event of an asthma attack that does not improve with bronchodilator medications.

Healthcare providers may monitor patients' breathing, conduct blood tests, and perform eye examinations during treatment with PULMICORT FLEXHALER. Patients should be encouraged to read, understand, and follow the detailed Patient Instructions for Use provided at the end of the leaflet, which explain how to prime and use PULMICORT FLEXHALER correctly.

Storage and Handling

The PULMICORT FLEXHALER inhaler is supplied in a configuration that cannot be refilled and must be discarded once empty. The inhaler is considered empty when the number zero (“0”) on the red background aligns with the center of the window. It is essential to discard the inhaler if it is used beyond this point.

For optimal storage, the inhaler should be kept in a dry place at a controlled room temperature of 20-25°C (68-77°F), in accordance with USP guidelines. The cover must remain tightly in place to maintain the integrity of the product. Additionally, it is crucial to keep the inhaler out of the reach of children to ensure safety.

Additional Clinical Information

Patients using PULMICORT FLEXHALER should be advised to rinse their mouths after 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. For those transitioning from oral corticosteroids, a gradual weaning from systemic corticosteroid use is recommended. Additionally, patients should 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 Pulmicort as submitted by Rubicon Holdings Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)