Asmanex Hfa

Description

ASMANEX HFA is a metered dose inhaler intended for oral inhalation only, delivering 50 mcg, 100 mcg, or 200 mcg of mometasone furoate per actuation. The active ingredient, mometasone furoate, is a corticosteroid with the chemical name 9,21-dichloro-11(Beta),17-dihydroxy-16(alpha)-methylpregna-1,4-diene-3,20-dione 17-(2-furoate). It appears as a white powder with an empirical formula of C27H30Cl2O6 and a molecular weight of 521.44 g/mol. Mometasone furoate is practically insoluble in water, slightly soluble in methanol, ethanol, and isopropanol, and soluble in acetone.

ASMANEX HFA is formulated as a hydrofluoroalkane (HFA-227: 1,1,1,2,3,3,3-heptafluoropropane) propelled pressurized metered dose inhaler. Each actuation delivers 60, 115, or 225 mcg of mometasone furoate in 69.6 mg of suspension from the valve, while the actuator delivers 50, 100, or 200 mcg of mometasone furoate. Additionally, ASMANEX HFA contains ethanol as a cosolvent and oleic acid as a surfactant.

Uses and Indications

ASMANEX HFA is indicated for the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older.

ASMANEX HFA is not indicated for the relief of acute bronchospasm.

Dosage and Administration

For oral inhalation only.

In the treatment of asthma for patients aged 12 years and older, the recommended dosage is 2 inhalations of ASMANEX HFA, either 100 mcg or 200 mcg, administered twice daily. The starting dosage should be determined based on the patient's prior asthma therapy.

For patients aged 5 to less than 12 years, the recommended dosage is 2 inhalations of ASMANEX HFA 50 mcg, also administered twice daily.

Healthcare professionals should ensure that patients are instructed on the proper inhalation technique to maximize the therapeutic effects of the medication.

Contraindications

Use of ASMANEX HFA is contraindicated in the following situations:

Patients requiring primary treatment for status asthmaticus or acute episodes of asthma that necessitate intensive measures. This is due to the potential for inadequate response in such critical conditions.

Additionally, ASMANEX HFA should not be used in individuals with a known hypersensitivity to any of its ingredients, as this may lead to severe allergic reactions.

Warnings and Precautions

ASMANEX HFA is not indicated for the relief of acute asthma symptoms. Patients experiencing rapidly deteriorating asthma should undergo immediate re-evaluation to ensure appropriate management.

Localized infections, particularly Candida albicans infections of the mouth and throat, may occur in patients using ASMANEX HFA. It is essential to monitor patients periodically for any adverse effects on the oral cavity. Patients should be advised to rinse their mouth with water and expectorate the contents after dosing to minimize the risk of oral infections.

Immunosuppression is a potential concern with ASMANEX HFA, as it may exacerbate existing infections, including tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex infections. In susceptible individuals, there is a risk of a more severe or fatal course of chickenpox or measles. Caution is advised when prescribing ASMANEX HFA to patients with these infections due to the potential for worsening conditions.

When transitioning patients from systemic corticosteroids to ASMANEX HFA, there is a risk of impaired adrenal function. It is recommended to wean patients slowly from oral corticosteroids to mitigate this risk.

Hypercorticism and adrenal suppression may occur, particularly with high dosages or in individuals who are susceptible. Should these changes manifest, ASMANEX HFA should be discontinued gradually.

The use of ASMANEX HFA in conjunction with strong cytochrome P450 3A4 inhibitors, such as ritonavir, may lead to increased systemic corticosteroid effects. Caution is warranted in such cases.

In the event of paradoxical bronchospasm, ASMANEX HFA should be discontinued immediately, and alternative therapy should be initiated.

Hypersensitivity reactions, including anaphylaxis, may occur in some patients. Symptoms can include urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reactions. If any of these reactions occur, ASMANEX HFA should be discontinued.

Patients with major risk factors for decreased bone mineral density should be monitored for potential decreases in bone mineral content while using ASMANEX HFA. Additionally, the growth of pediatric patients should be closely monitored during treatment.

Long-term use of ASMANEX HFA may lead to ocular complications such as glaucoma and cataracts. Patients developing ocular symptoms or those requiring prolonged treatment should be considered for referral to an ophthalmologist for further evaluation.

Side Effects

Patients using ASMANEX HFA may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

The most common adverse reactions reported include nasopharyngitis, headache, sinusitis, bronchitis, and influenza. These reactions were observed in clinical trials and are typically mild in nature.

Serious adverse reactions warrant careful consideration and monitoring. Patients may experience deterioration of asthma and acute episodes; ASMANEX HFA is not intended for the relief of acute symptoms, and patients should be re-evaluated promptly if their asthma worsens. Localized infections, particularly Candida albicans infections of the mouth and throat, may occur. It is advised that patients rinse their mouths with water and spit out the contents after dosing to mitigate this risk.

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

When transferring patients from systemic corticosteroids to ASMANEX HFA, there is a risk of impaired adrenal function. It is recommended to wean patients slowly from oral steroids to minimize this risk. Hypercorticism and adrenal suppression may occur, particularly with high dosages or in susceptible individuals; if such changes are observed, ASMANEX HFA should be discontinued gradually.

The use of strong cytochrome P450 3A4 inhibitors, such as ritonavir, may increase the risk of systemic corticosteroid effects when used in conjunction with ASMANEX HFA. Additionally, paradoxical bronchospasm may occur; if this happens, ASMANEX HFA should be discontinued, and alternative therapy should be initiated.

Hypersensitivity reactions, including anaphylaxis, have been reported. Symptoms may include urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reactions. Discontinuation of ASMANEX HFA is necessary if such reactions occur.

Patients with major risk factors for decreased bone mineral density should be monitored, as decreases in bone mineral density have been noted. Furthermore, the growth of pediatric patients should be monitored during treatment. Long-term use of ASMANEX HFA may also lead to the development of glaucoma and cataracts, and referral to an ophthalmologist should be considered for patients exhibiting ocular symptoms.

Chronic overdosage of ASMANEX HFA may result in signs and symptoms of hypercorticism, necessitating careful management of dosage.

Drug Interactions

Strong inhibitors of cytochrome P450 3A4, such as ritonavir, should be used with caution in conjunction with this medication. The co-administration may lead to an increase in systemic corticosteroid effects, necessitating careful monitoring of the patient for signs of corticosteroid-related adverse effects.

Currently, there is no information available regarding drug and laboratory test interactions.

Packaging & NDC

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

Pediatric Use

The safety and effectiveness of ASMANEX HFA have been established in patients aged 12 years and older through two clinical trials lasting 12 and 26 weeks. In these trials, 32 patients aged 12 to 17 years were treated with ASMANEX HFA, and no significant differences in effectiveness were noted compared to patients aged 18 years and older.

For pediatric patients aged 5 to less than 12 years, the safety and effectiveness of ASMANEX HFA 50 mcg, administered as two inhalations twice daily, have been demonstrated in clinical trials of up to 24 weeks. The safety profile and overall effectiveness in this age group were consistent with those observed in patients aged 12 years and older.

However, the safety and effectiveness of ASMANEX HFA have not been established in children younger than 5 years. It is important to note that controlled clinical studies indicate that inhaled corticosteroids, including ASMANEX HFA, may lead to a reduction in growth velocity in pediatric patients, with an average reduction of approximately 1 cm per year (ranging from 0.3 to 1.8 cm). This reduction appears to be dose- and duration-dependent and has been observed without laboratory evidence of HPA axis suppression. The long-term implications of this growth reduction, including its potential impact on final adult height, remain unknown.

Routine monitoring of growth in children and adolescents receiving orally inhaled corticosteroids, such as ASMANEX HFA, is recommended, utilizing methods such as stadiometry. If growth suppression is suspected in a child or adolescent on corticosteroids, it is essential to consider their sensitivity to this effect. The potential growth effects of prolonged treatment should be carefully weighed against the clinical benefits and risks associated with alternative therapies. To minimize systemic effects, each patient should be titrated to the lowest effective dose of ASMANEX HFA.

Geriatric Use

In clinical trials involving ASMANEX HFA, a total of 38 patients aged 65 years and older were treated, including 3 patients who were 75 years of age and older. The duration of these trials was 12 and 26 weeks.

No overall differences in safety or effectiveness were observed between elderly patients and their younger counterparts. However, it is important to note that greater sensitivity in some older individuals cannot be ruled out.

Based on the available data for ASMANEX HFA, no dosage adjustments are warranted for geriatric patients. Nonetheless, healthcare providers should remain vigilant and monitor elderly patients closely for any potential variations in response to treatment.

Pregnancy

There are no randomized clinical studies of ASMANEX HFA in pregnant women; however, clinical considerations exist regarding its use in this population. Animal reproduction studies have demonstrated that mometasone furoate can lead to increased fetal malformations and decreased fetal survival and growth when administered to pregnant mice, rats, or rabbits at doses producing exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m² or AUC basis. It is important to note that experience with oral corticosteroids indicates that rodents may be more susceptible to teratogenic effects from corticosteroid exposure than humans.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2 to 4% and 15 to 20%, respectively; however, the specific risk for the indicated population remains unknown. Pregnant women with poorly or moderately controlled asthma face an increased risk of several perinatal adverse outcomes, including preeclampsia, prematurity, low birth weight, and small for gestational age neonates. Therefore, it is crucial for pregnant women with asthma to be closely monitored, with medication adjustments made as necessary to maintain optimal asthma control.

In embryofetal development studies, mometasone furoate produced cleft palate in pregnant mice at an exposure approximately one-third of the MRHD and decreased fetal survival at an exposure equivalent to the MRHD. In studies involving pregnant rats, the drug caused fetal umbilical hernia at exposures approximately 6 times the MRHD and delays in fetal ossification at exposures approximately 3 times the MRHD. Additionally, when administered throughout pregnancy or late in gestation, mometasone furoate resulted in prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure approximately 8 times the MRHD.

Embryofetal development studies conducted with pregnant rabbits revealed that mometasone furoate, when administered via the topical dermal route, caused multiple malformations in fetuses at an exposure approximately 3 times the MRHD. Conversely, when administered orally, the drug led to increased fetal resorptions and cleft palate and/or head malformations at an exposure approximately 1/2 of the MRHD. Given these findings, the use of ASMANEX HFA during pregnancy should be approached with caution, weighing the potential risks against the benefits of asthma control.

Lactation

There are no available data on the presence of ASMANEX HFA in human milk, the effects on the breastfed child, or the effects on milk production. However, other inhaled corticosteroids, which are similar to mometasone furoate, have been found to be present in human milk.

When considering the use of ASMANEX HFA in lactating mothers, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for the medication. Additionally, potential adverse effects on the breastfed infant from ASMANEX HFA or from the underlying maternal condition should be taken into account.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments, special monitoring, or safety considerations provided in the text. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to this population. Regular assessment of renal function may be warranted to ensure safe and effective use of the medication in patients with reduced kidney function.

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

Chronic overdosage of mometasone furoate may lead to the development of signs and symptoms consistent with hypercorticism. Healthcare professionals should be vigilant for these manifestations in patients who may have ingested excessive amounts of the medication.

In clinical studies, single oral doses of mometasone furoate up to 8000 mcg have been administered to adult subjects without any adverse reactions reported. This suggests a relatively high threshold for acute overdosage; however, the potential for chronic overdosage and its associated effects should not be underestimated.

In the event of suspected overdosage, it is recommended that healthcare providers assess the patient for symptoms of hypercorticism and manage accordingly. Monitoring and supportive care may be necessary, depending on the severity of the symptoms presented.

Nonclinical Toxicology

In a 2-year carcinogenicity study conducted in Sprague Dawley rats, mometasone furoate did not demonstrate a statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg, which is approximately 14 times the maximum recommended human dose (MRHD) based on area under the curve (AUC) calculations. Similarly, a 19-month carcinogenicity study in Swiss CD-1 mice revealed no statistically significant increase in tumor incidence at inhalation doses up to 160 mcg/kg, approximately 9 times the MRHD on an AUC basis.

Mometasone furoate was found to increase chromosomal aberrations in an in vitro assay using Chinese hamster ovary cells; however, this effect was not observed in an in vitro assay using Chinese hamster lung cells. The compound was not mutagenic in the Ames test or the mouse lymphoma assay, and it did not exhibit clastogenic effects in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Additionally, mometasone furoate did not induce unscheduled DNA synthesis in vivo in rat hepatocytes.

In reproductive studies involving rats, no impairment of fertility was observed at subcutaneous doses up to 15 mcg/kg, which is approximately 8 times the MRHD on an AUC basis.

Postmarketing Experience

Worsening asthma or sudden asthma attacks have been reported following the use of inhaled mometasone furoate. Hypersensitivity reactions, including urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reactions, may occur after administration of ASMANEX HFA. Localized infections with Candida albicans have been observed in the mouth and pharynx in some patients.

Adrenal insufficiency, which can lead to serious outcomes, including death, may occur when transitioning from oral corticosteroid medications to inhaled corticosteroid therapies. Increased wheezing immediately after taking ASMANEX HFA has also been reported. Serious allergic reactions have been documented; patients are advised to discontinue ASMANEX HFA and seek immediate medical attention if symptoms such as rash, hives, or swelling of the face, mouth, or tongue occur.

Additional concerns include lower bone mineral density, which may pose risks for individuals predisposed to osteoporosis, and potential for slowed growth in children, necessitating regular monitoring of growth parameters. Eye-related issues, such as glaucoma, cataracts, and blurred vision, have been reported, highlighting the importance of regular eye examinations during treatment with ASMANEX HFA.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use, prior to starting ASMANEX HFA. It is important to inform patients that ASMANEX HFA is not indicated for the relief of acute asthma symptoms; therefore, extra doses should not be used for this purpose. ASMANEX HFA is not a bronchodilator and should not be utilized to treat status asthmaticus or to relieve acute asthma symptoms. Patients should be prescribed an inhaled, short-acting beta2-agonist, such as albuterol, and instructed on its proper use.

Patients must be instructed to seek immediate medical attention if they experience worsening symptoms, a significant decrease in lung function as outlined by their physician, or an increased need for inhalations of a short-acting beta2-agonist beyond their usual amount. It is crucial to advise patients not to increase the dose or frequency of ASMANEX HFA, and to adhere to the prescribed regimen of two inhalations twice daily. If a dose is missed, patients should take their next dose at the same time they normally would.

Patients should be cautioned against stopping or reducing ASMANEX HFA therapy without consulting their healthcare provider, as symptoms may recur upon discontinuation. Additionally, patients should be made aware of the risk of localized infections with Candida albicans in the mouth and pharynx. If oropharyngeal candidiasis develops, appropriate local or systemic antifungal therapy should be initiated while continuing ASMANEX HFA therapy, although temporary interruption of ASMANEX HFA may be necessary under close medical supervision. After each dose, patients should rinse their mouth with water and spit out the contents without swallowing to help mitigate this risk.

Healthcare providers should warn patients on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and to consult their physician immediately if exposed. 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 ASMANEX HFA may lead to systemic corticosteroid effects, including hypercorticism and adrenal suppression. It is essential to instruct patients that deaths due to adrenal insufficiency have occurred during and after transitioning from systemic corticosteroids, and they should be advised to taper off systemic corticosteroids slowly when switching to ASMANEX HFA.

For patients at increased risk for decreased bone mineral density (BMD), the use of corticosteroids may pose an additional risk, and monitoring or treatment for this condition should be considered. It is also important to inform patients that orally inhaled corticosteroids, including ASMANEX HFA, may reduce growth velocity in pediatric patients, necessitating close monitoring of their growth by healthcare providers.

Patients should be made aware that long-term use of inhaled corticosteroids may increase the risk of eye problems, such as glaucoma or cataracts, and regular eye examinations should be considered. Additionally, hypersensitivity reactions, including urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylactic reactions, may occur after administration of ASMANEX HFA. Patients should be instructed to discontinue ASMANEX HFA if any such reactions occur.

Finally, healthcare providers should emphasize the importance of using ASMANEX HFA at regular intervals, as its effectiveness is contingent upon consistent use. Maximum benefit may not be achieved for one week or longer after initiating treatment. If symptoms do not improve after two weeks of therapy or if the condition worsens, patients should be advised to contact their physician. Patients should also be instructed to carefully follow the following guidelines: read the Patient Information before use, remove the cap from the mouthpiece of the actuator before use, rinse their mouth with water and spit out the contents after dosing, avoid removing the canister from the actuator, and refrain from washing the inhaler in water, instead cleaning the mouthpiece with a dry wipe every seven days.

Storage and Handling

The product is supplied in a configuration that includes an inhaler actuator and a canister. It is essential to store the inhaler at a controlled room temperature of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C and 30°C (59°F to 86°F). For optimal performance, the canister should be kept at room temperature prior to use.

After priming, the inhaler must be stored with the mouthpiece facing down or in a horizontal position. Prior to use, the canister should be shaken well, and the cap from the mouthpiece of the actuator should be removed.

It is crucial to keep the inhaler out of reach of children and to avoid spraying it in the eyes. The contents are under pressure; therefore, the canister must not be punctured. Additionally, the inhaler should not be used or stored near heat sources or open flames, as exposure to temperatures exceeding 120°F may lead to bursting. The container must never be thrown into a fire or incinerator.

The inhaler should be discarded once the labeled number of actuations has been reached, indicated by the dose counter reading "0."

Additional Clinical Information

Patients using ASMANEX HFA should be advised to rinse their mouths with water and expectorate the contents after dosing to minimize the risk of oropharyngeal candidiasis. Additionally, those who have previously been maintained on a daily dose of 20 mg or more of prednisone (or its equivalent) are recommended to carry a medical identification card. This card serves to inform healthcare providers that they may require supplementary systemic corticosteroids during times of stress or in the event of a severe asthma attack.

FDA Insert (PDF)

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

View full prescribing information (PDF)