Pulmicort

Description

Budesonide, the active ingredient in PULMICORT FLEXHALER, 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 for budesonide is C25H34O6, and it has a molecular weight of 430.5 g/mol.

Budesonide appears as a white to off-white, tasteless, and odorless powder. It is practically insoluble in water and heptane, sparingly soluble in ethanol, and freely soluble in chloroform. The partition coefficient between octanol and water at pH 7.4 is 1.6 x 10^3.

PULMICORT FLEXHALER is an inhalation-driven multi-dose dry powder inhaler that delivers a formulation containing 1 mg of micronized budesonide per actuation, along with micronized lactose monohydrate, which includes trace levels of milk proteins. Each actuation of PULMICORT FLEXHALER 180 mcg provides 160 mcg of budesonide from the mouthpiece, while each actuation of PULMICORT FLEXHALER 90 mcg delivers 80 mcg of budesonide. The PULMICORT FLEXHALER 180 mcg contains 120 actuations, and the PULMICORT FLEXHALER 90 mcg contains 60 actuations.

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 should not use this product. Additionally, individuals with severe hypersensitivity to milk proteins or any of the ingredients in PULMICORT FLEXHALER are also contraindicated for its use.

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 this medication to patients with such infections, 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 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 these 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 important 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 that any potential effects on growth are identified and managed appropriately.

Patients should be monitored for the development of glaucoma and cataracts, as these conditions may be exacerbated by the use of PULMICORT FLEXHALER.

Paradoxical bronchospasm may occur in some patients. If this reaction is observed, 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, as these conditions may arise during treatment.

To ensure safe use, 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 mouths 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, PULMICORT FLEXHALER should be discontinued promptly.

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 advised when prescribing to patients with these infections, as a more serious or even fatal course of chickenpox or measles can occur in susceptible individuals.

When transferring patients from systemic corticosteroid therapy to 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 should be undertaken.

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. Additionally, the growth of pediatric patients should be closely monitored during treatment.

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, PULMICORT FLEXHALER should be discontinued, and alternative therapy should be initiated.

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

While the potential for acute toxic effects following an overdose of PULMICORT FLEXHALER is low, systemic corticosteroid effects such as hypercorticism may occur with excessive doses used for prolonged periods. Postmarketing experience indicates that acute overdose of inhaled budesonide often remains asymptomatic, although the use of excessive doses (up to 6400 mcg daily) for extended durations has been associated with systemic corticosteroid effects.

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 heightened effects and adjust treatment accordingly based on the patient's clinical response.

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 pediatric patients aged 6 to 17 years, treatment with PULMICORT FLEXHALER administered twice daily demonstrated efficacy comparable to that observed in adults aged 18 years and older. The type and frequency of adverse events reported in this age group 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 among 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 traditional HPA-axis function tests. The long-term implications of this growth reduction, including its impact on final adult height, remain uncertain, 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 exhibited a 1.1-centimeter reduction in growth compared to a placebo group 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, the conclusions of 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 of 445 mcg/day) or via a pressurized metered-dose inhaler at doses up to 1200 mcg/day (mean daily dose of 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 remain to be fully elucidated.

Monitoring of growth in pediatric patients receiving orally inhaled corticosteroids, including PULMICORT FLEXHALER, is recommended, utilizing methods such as stadiometry. If growth suppression is observed in a child or adolescent on corticosteroid therapy, 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 control asthma while minimizing systemic effects.

Geriatric Use

In controlled clinical studies involving inhaled budesonide, a total of 153 patients aged 65 years and older were included, with 11 patients treated with PULMICORT FLEXHALER and one patient aged 75 years or older. No overall differences in safety were observed between these 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 elderly and younger patients.

Additionally, other clinical or medical surveillance experiences have not identified any significant differences in responses to treatment between elderly and younger patients. Despite these findings, it is important to approach dose selection for geriatric patients with caution. It is generally recommended to start at the low end of the dosing range for elderly patients, 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. Careful monitoring and consideration of these factors are essential to ensure the safety and efficacy of treatment in this population.

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).

In animal reproduction studies, budesonide administered by the subcutaneous route 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. In a fertility and reproduction study, budesonide resulted in decreased prenatal viability and viability in pups at birth and during lactation at doses 0.1 times the MRHDID, while fetal loss, decreased fetal weight, and skeletal abnormalities were noted at doses 0.3 times the MRHDID in pregnant rabbits. In an embryo-fetal development study in pregnant rats, similar adverse fetal effects were observed at doses approximately 4 times the MRHDID, but no structural abnormalities or embryocidal effects were seen 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 the potential risks of budesonide exposure when considering treatment options for 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 microgram per square meter (mcg/m²) basis, maternal subcutaneous doses of 20 mcg/kg/day and above resulted in decreased maternal body-weight gain and reduced offspring survival.

In a peri-and post-natal development study involving rats, budesonide did not impact delivery; however, it adversely affected the growth and development of the offspring. At doses of 0.1 times the MRHDID and higher, there was a noted decrease in mean body weights at birth and during lactation, alongside reduced survival rates of the offspring. These 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 risks to breastfed infants may be significant.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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

Acute overdose of PULMICORT FLEXHALER is associated with a low potential for toxic effects. However, when excessive doses are administered over extended periods, there is a risk of systemic corticosteroid effects, notably hypercorticism.

Clinical observations indicate that the administration of another budesonide-containing dry powder inhaler at a dosage of 3200 mcg daily for six weeks resulted in a significant reduction of 27% in the plasma cortisol response to a 6-hour infusion of ACTH, compared to a placebo group, which exhibited a +1% change. In comparison, a regimen of 10 mg prednisone daily led to a 35% reduction in the plasma cortisol response to ACTH.

Postmarketing data reveal that acute overdoses of inhaled budesonide frequently remain asymptomatic. Nevertheless, the use of excessive doses, reaching up to 6400 mcg daily over prolonged durations, has been associated with systemic corticosteroid effects, including hypercorticism.

In the event of suspected overdose, it is recommended that healthcare professionals monitor the patient for signs of hypercorticism and manage symptoms accordingly. Regular assessment of plasma cortisol levels may be warranted to evaluate the impact of prolonged high-dose therapy.

Nonclinical Toxicology

Fertility and reproductive performance were 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 observed. No such effects were noted at a dose of 5 mcg/kg, which is approximately 0.03 times the MRHDID in adults on a mcg/m² basis.

In a 104-week oral study conducted in Sprague-Dawley rats, a statistically significant increase in the incidence of gliomas was observed 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 noted in male rats at oral doses up to 25 mcg/kg, approximately 0.2 times the MRHDID, and in female rats at oral doses up to 50 mcg/kg, approximately 0.3 times the MRHDID. In two additional two-year studies involving male Fischer and Sprague-Dawley rats, budesonide did not cause gliomas at an oral dose of 50 mcg/kg. However, in male Sprague-Dawley rats, a statistically significant increase in the incidence of hepatocellular tumors was observed at the same oral 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. 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

Postmarketing experience has identified several adverse events associated with the use of PULMICORT FLEXHALER. Hypersensitivity reactions, including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm, have been reported. In the event of such reactions, discontinuation of PULMICORT FLEXHALER is advised.

There is an increased risk of infections due to immune system effects, particularly in patients taking medications that may weaken their immune response. Patients are advised to avoid contact with individuals who have contagious diseases, such as chickenpox or measles, during treatment.

Adrenal insufficiency has been reported, characterized by symptoms such as tiredness, weakness, nausea, vomiting, and low blood pressure. Monitoring for this condition is recommended.

Additionally, a decrease in bone mineral density has been observed, necessitating regular assessments by healthcare providers during treatment. In pediatric patients, there have been reports of slowed or delayed growth, warranting regular growth checks.

Eye-related issues, including glaucoma and cataracts, have also been noted, and patients should undergo routine eye examinations while using PULMICORT FLEXHALER. Furthermore, instances of increased wheezing immediately following administration have been reported, highlighting the importance of having a short-acting beta-agonist (rescue inhaler) available for the management of 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 beta-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 beta-agonists; an increased need for inhalations of inhaled, short-acting beta-agonists; or a significant decrease in lung function as outlined by the physician. Additionally, patients should 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. Patients should also be informed about the potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

Patients should be advised that PULMICORT FLEXHALER may cause systemic corticosteroid effects, including hypercorticism and adrenal suppression. It is important 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 PULMICORT FLEXHALER.

Patients at increased risk for decreased bone mineral density 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. Physicians should closely monitor the growth of children and adolescents taking corticosteroids by any route.

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 time, patients should contact their physician.

Patients should receive careful instruction 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 did not feel the medication.

Patients should rinse their mouth with water and spit it out after each dose of PULMICORT FLEXHALER to reduce the risk of developing a fungal infection (thrush) 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 take more puffs than prescribed.

Patients should always have a short-acting beta-agonist medication available. They should use this medication if they experience breathing problems between doses of PULMICORT FLEXHALER or during a sudden asthma attack. Patients 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 using corticosteroid medications for an extended period and are now having their dose lowered or stopped, it is advisable to carry a medical alert card. This card should indicate that they may require increased corticosteroids during times of stress or during 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 to ensure safety and efficacy.

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 is aligned with the middle of the window. It is important 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 essential 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, particularly for patients who have been on 20 mg or more per day of prednisone (or its equivalent), as they may be more susceptible to adrenal insufficiency. Additionally, patients should carry a medical identification card indicating the need for supplementary systemic corticosteroids during periods of stress or severe asthma attacks.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Pulmicort as submitted by H2-Pharma LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)