Asmanex

Description

Mometasone furoate, the active ingredient in ASMANEX TWISTHALER, is a corticosteroid with the chemical designation 9,21-dichloro-11(Beta),17-dihydroxy-16(alpha)-methylpregna-1,4-diene-3,20-dione 17-(2-furoate). It has an empirical formula of C27H30Cl2O6 and a molecular weight of 521.44 Daltons.

The ASMANEX TWISTHALER is available in two formulations: 110 mcg and 220 mcg. These are cap-activated, inhalation-driven, multidose dry powder inhalers that contain mometasone furoate and anhydrous lactose, which may include trace amounts of milk proteins. Each actuation of the inhaler delivers approximately 0.75 mg or 1.5 mg of inhalation powder, providing 110 mcg or 220 mcg of mometasone furoate, respectively. Based on in vitro testing at flow rates of 30 L/min and 60 L/min with a constant volume of 2 L, the mouthpiece delivers 100 mcg or 200 mcg of mometasone furoate, respectively.

In vitro studies indicate that the emitted amount of mometasone furoate does not significantly vary for flow rates between 28.3 L/min and 70 L/min at a constant volume of 2 L. However, the actual drug delivery to the lung is influenced by patient-specific factors, including inspiratory flow and peak inspiratory flow through the device. In adult and adolescent patients (aged ≥12 years) with varying asthma severity, the mean peak inspiratory flow rate was recorded at 69 L/min (range: 54–77 L/min). For pediatric patients (aged 5-12 years) diagnosed with asthma, the mean peak inspiratory flow rate for the 5- to 8-year-old subgroup was greater than 50 L/min (minimum of 46 L/min), while the 9- to 12-year-old subgroup exhibited a mean peak inspiratory flow rate greater than 60 L/min (minimum of 48 L/min).

Uses and Indications

ASMANEX TWISTHALER is indicated for the maintenance treatment of asthma as prophylactic therapy in patients aged 4 years and older.

Limitations of use include that ASMANEX TWISTHALER is not indicated for the relief of acute bronchospasm. Additionally, it is not approved for use in children under 4 years of age.

Dosage and Administration

ASMANEX TWISTHALER is intended for oral inhalation only. Patients should be instructed to inhale rapidly and deeply. Following administration, patients must rinse their mouth with water and spit out the contents without swallowing.

For patients aged 12 years and older who have previously received bronchodilators alone or inhaled corticosteroids, the recommended starting dose is 220 mcg once daily in the evening, with a highest recommended daily dose of 440 mcg.

For patients aged 12 years and older who have previously received oral corticosteroids, the recommended starting dose is 440 mcg twice daily, with a highest recommended daily dose of 880 mcg.

For children aged 4 to 11 years, the recommended starting dose is 110 mcg once daily in the evening, with a highest recommended daily dose of 110 mcg.

Contraindications

Use of ASMANEX TWISTHALER is contraindicated in patients with status asthmaticus or other acute episodes of asthma requiring intensive measures. Additionally, it is contraindicated in individuals with a known hypersensitivity to milk proteins or any components of ASMANEX TWISTHALER.

Warnings and Precautions

Patients using ASMANEX TWISTHALER should be monitored periodically for signs of Candida albicans infection in the mouth and pharynx. It is recommended that patients rinse their mouth with water and spit out the contents without swallowing after administration to minimize the risk of oral infections.

ASMANEX TWISTHALER 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 of their condition.

Hypersensitivity reactions, including anaphylaxis, angioedema, pruritus, and rash, have been reported in patients using ASMANEX TWISTHALER. Should any of these reactions occur, the use of ASMANEX TWISTHALER must be discontinued immediately.

Caution is advised in patients with existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as those with ocular herpes simplex. The use of ASMANEX TWISTHALER may exacerbate these conditions, potentially leading to more severe or even fatal outcomes in susceptible individuals, particularly in cases of chickenpox or measles.

When transitioning patients from oral corticosteroids to ASMANEX TWISTHALER, there is a risk of impaired adrenal function. It is essential to taper systemic corticosteroids slowly to mitigate this risk.

Long-term use of ASMANEX TWISTHALER may lead to hypercorticism and suppression of hypothalamic-pituitary-adrenal (HPA) function, especially at high dosages or in susceptible individuals. If such changes are observed, the discontinuation of ASMANEX TWISTHALER should be done gradually.

Patients receiving long-term treatment with ASMANEX TWISTHALER should be monitored for a reduction in bone mineral density, particularly those with major risk factors for decreased bone mineral content.

In pediatric patients, routine monitoring of growth is necessary, as ASMANEX TWISTHALER may suppress growth.

Patients using ASMANEX TWISTHALER for an extended period should be evaluated for the development of glaucoma and cataracts. Referral to an ophthalmologist should be considered for those who exhibit ocular symptoms.

Paradoxical bronchospasm may occur with the use of ASMANEX TWISTHALER. In the event of bronchospasm, it is crucial to treat the condition immediately with a fast-acting inhaled bronchodilator and discontinue ASMANEX TWISTHALER.

Caution is warranted when ASMANEX TWISTHALER is used in conjunction with strong cytochrome P450 3A4 inhibitors, such as ritonavir, due to the risk of increased systemic corticosteroid effects.

Side Effects

Patients receiving ASMANEX TWISTHALER may experience a range of adverse reactions, which can be categorized into common and serious reactions.

Common adverse reactions reported include headache, allergic rhinitis, pharyngitis, upper respiratory tract infection, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, and dyspepsia. These reactions were observed in clinical trials and may vary in frequency among patients.

Serious adverse reactions necessitate immediate medical attention and include hypersensitivity reactions such as anaphylaxis, angioedema, pruritus, and rash. In the event of such reactions, ASMANEX TWISTHALER should be discontinued. Additionally, patients may experience deterioration of asthma or acute episodes; it is important to note that ASMANEX TWISTHALER is not intended for the relief of acute symptoms, and patients should be re-evaluated promptly during episodes of rapidly deteriorating asthma.

There is a potential risk of worsening existing infections, including tuberculosis and various fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex. In susceptible patients, there may be a more serious or even fatal course of chickenpox or measles. Patients transitioning from oral corticosteroids to inhaled corticosteroids may experience impaired adrenal function; therefore, a gradual tapering of systemic corticosteroids is recommended.

Long-term administration of ASMANEX TWISTHALER may lead to hypercorticism, characterized by suppression of hypothalamic-pituitary-adrenal (HPA) function, particularly at high dosages or in susceptible individuals. If such changes occur, discontinuation of ASMANEX TWISTHALER should be done gradually. Furthermore, there is a risk of reduction in bone mineral density with long-term use, necessitating monitoring in patients with major risk factors for decreased bone mineral content.

In pediatric patients, suppression of growth has been observed, and routine monitoring of growth is advised. Patients using ASMANEX TWISTHALER long-term or those who develop ocular symptoms should be considered for referral to an ophthalmologist due to the risk of glaucoma and cataracts. Paradoxical bronchospasm may also occur; in such cases, immediate treatment with a fast-acting inhaled bronchodilator is required, and ASMANEX TWISTHALER should be discontinued.

Chronic overdosage of ASMANEX TWISTHALER may result in signs and symptoms of hypercorticism. Special caution is warranted for patients with status asthmaticus or other acute episodes of asthma requiring intensive measures, as well as for those with a known hypersensitivity to milk proteins or any ingredients of ASMANEX TWISTHALER.

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 Asmanex (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 TWISTHALER for the maintenance treatment of asthma as prophylactic therapy have been established in pediatric patients aged 4 years and older. In children aged 12 years and older, the use of ASMANEX TWISTHALER is supported by evidence from adequate and well-controlled clinical trials. For pediatric patients aged 4 to 11 years, the use is also supported by clinical trials, including a 12-week study involving 630 patients and a 52-week safety trial with 152 patients.

Controlled clinical studies indicate that inhaled corticosteroids, including ASMANEX TWISTHALER, may lead to a reduction in growth velocity in pediatric patients. The mean reduction observed was approximately 1 cm per year, with a range of 0.3 to 1.8 cm per year, which appears to be dose- and duration-dependent. 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.

Routine monitoring of growth in children and adolescents (aged 4 years and older) receiving orally inhaled corticosteroids, including ASMANEX TWISTHALER, is recommended, typically through stadiometry. A 52-week, placebo-controlled study assessed the growth effects of ASMANEX TWISTHALER in 187 prepubescent children (131 males and 56 females) aged 4 to 9 years with asthma, who were previously maintained on an inhaled beta-agonist.

The potential growth effects of prolonged treatment with orally inhaled corticosteroids should be carefully weighed against the clinical benefits and the availability of safe and effective non-corticosteroid alternatives. To minimize systemic effects, it is advised that each patient be titrated to the lowest effective dose of ASMANEX TWISTHALER.

Geriatric Use

In controlled clinical trials, a total of 175 patients aged 65 years and older, including 23 patients aged 75 years and older, have been treated with ASMANEX TWISTHALER. The data from these trials indicate that there are no overall differences in safety or effectiveness between elderly patients and their younger counterparts.

However, it is important to note that while clinical experience has not identified significant differences in responses between geriatric patients and younger individuals, the possibility of greater sensitivity in some older patients cannot be excluded. Therefore, healthcare providers should exercise caution when prescribing ASMANEX TWISTHALER to elderly patients, considering the potential for increased sensitivity and the need for careful monitoring of therapeutic responses.

Pregnancy

There are no adequate and well-controlled studies of ASMANEX TWISTHALER in pregnant women. Clinical considerations must be taken into account when prescribing ASMANEX TWISTHALER to pregnant patients. Animal reproduction studies have demonstrated that mometasone furoate can cause increased fetal malformations and decreased fetal survival and growth in pregnant mice, rats, and rabbits at doses producing exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m² or AUC basis. However, 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 unknown; however, it is generally accepted that the risk of major birth defects in clinically recognized pregnancies is approximately 2 to 4%, while the risk of miscarriage is estimated to be between 15 to 20%. 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 neonates. Therefore, pregnant women with asthma should be closely monitored, and medication should be adjusted as necessary to maintain optimal asthma control.

Embryofetal development studies have shown that mometasone furoate can lead to significant adverse outcomes. In one study involving pregnant mice dosed throughout the period of organogenesis, cleft palate was observed at an exposure approximately 1/3 of the MRHD, along with decreased fetal survival at an exposure equivalent to the MRHD. In pregnant rats, exposure to mometasone furoate resulted in fetal umbilical hernia at approximately 6 times the MRHD and delays in fetal ossification at approximately 3 times the MRHD. Additionally, another reproductive toxicity study indicated that pregnant rats dosed throughout pregnancy or late in gestation experienced prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure approximately 6 times the MRHD.

In studies conducted with pregnant rabbits, mometasone furoate administered via topical dermal and oral routes throughout the period of organogenesis resulted in multiple malformations in fetuses at an exposure approximately 3 times the MRHD and increased fetal resorptions, cleft palate, and/or head malformations at an exposure approximately 1/2 of the MRHD, respectively. Given these findings, healthcare professionals should weigh the potential risks and benefits when considering the use of ASMANEX TWISTHALER in pregnant patients.

Lactation

There are no available data on the presence of ASMANEX TWISTHALER 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 TWISTHALER in lactating mothers, it is important to weigh the developmental and health benefits of breastfeeding against the mother's clinical need for the medication. Additionally, potential adverse effects on the breastfed infant from ASMANEX TWISTHALER or from the underlying maternal condition should be taken into account.

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

Chronic overdosage of the medication may lead to the development of signs and symptoms associated with hypercorticism. Healthcare professionals should be vigilant for these manifestations, which may include features such as weight gain, hypertension, and glucose intolerance.

In the case of acute overdose, the low systemic bioavailability of the drug, coupled with the absence of acute drug-related systemic findings observed in clinical studies, suggests that such occurrences are unlikely to necessitate any specific treatment beyond careful observation. Monitoring the patient for any emerging symptoms is recommended, ensuring that any potential complications are promptly addressed.

Nonclinical Toxicology

In mice, mometasone furoate was associated with teratogenic effects, including the occurrence of cleft palate at subcutaneous doses of 60 mcg/kg and above, which is below the maximum recommended daily inhalation dose in adults on an mcg/m² basis. Additionally, fetal survival was compromised at a dose of 180 mcg/kg, approximately equal to the maximum recommended daily inhalation dose in adults on an mcg/m² basis. In rabbits, multiple malformations such as flexed front paws, gallbladder agenesis, umbilical hernia, and hydrocephaly were observed at topical dermal doses of 150 mcg/kg and above, which is about three times the maximum recommended daily inhalation dose in adults on an mcg/m² basis. An oral study indicated that at a dose of 700 mcg/kg, mometasone furoate increased resorptions and caused cleft palate and/or head malformations, including hydrocephaly and domed head, which is less than the maximum recommended daily inhalation dose in adults on an area under the curve (AUC) basis. At a higher dose of 2800 mcg/kg, approximately two times the maximum recommended daily inhalation dose in adults on an AUC basis, most litters were either aborted or resorbed.

Non-teratogenic effects were noted at lower doses, with no toxicity observed at 20 mcg/kg, which is less than the maximum recommended daily inhalation dose in adults on an mcg/m² basis. A dose of 300 mcg/kg, approximately three times the maximum recommended daily inhalation dose in adults on an mcg/m² basis, resulted in delays in ossification without causing malformations. Similar effects were not observed at a dose of 7.5 mcg/kg, which is approximately three times the maximum recommended daily inhalation dose in adults on an AUC basis.

In a 2-year carcinogenicity study conducted in Sprague Dawley rats, mometasone furoate did not show a statistically significant increase in tumor incidence at inhalation doses up to 67 mcg/kg, which is approximately eight times the maximum recommended daily inhalation dose in adults on an AUC basis and two times the maximum recommended daily inhalation dose in pediatric patients based on an mcg/m² basis. 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 ten times the maximum recommended daily inhalation dose in adults on an AUC basis and two times the maximum recommended daily inhalation dose in pediatric patients based on an mcg/m² basis.

Mometasone furoate was found to increase chromosomal aberrations in an in vitro Chinese hamster ovary cell assay; however, this effect was not observed in an in vitro Chinese hamster lung cell assay. The compound was not mutagenic in the Ames test or mouse lymphoma assay, nor was it clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Furthermore, mometasone furoate did not induce unscheduled DNA synthesis in vivo in rat hepatocytes. In reproductive studies involving rats, no impairment of fertility was observed with subcutaneous doses up to 15 mcg/kg, which is approximately six times the maximum recommended daily inhalation dose in adults on an AUC basis.

When administered subcutaneously throughout pregnancy or during the later stages of pregnancy, a dose of 15 mcg/kg of mometasone furoate resulted in prolonged and difficult labor, as well as a reduction in the number of live births, birth weight, and early pup survival.

Postmarketing Experience

Postmarketing experience with ASMANEX TWISTHALER includes reports of hypersensitivity reactions, such as rash, pruritus, angioedema, and anaphylactic reactions. It is advised to discontinue ASMANEX TWISTHALER if such reactions occur. Additionally, anaphylactic reactions have been specifically reported in patients with a milk protein allergy. There have also been instances of worsening asthma or sudden asthma attacks associated with the use of inhaled mometasone furoate.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. It is important to inform patients 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 ASMANEX TWISTHALER therapy; however, therapy may need to be temporarily interrupted under close medical supervision.

Patients should be instructed to rinse their mouth after each inhalation. They must understand that ASMANEX TWISTHALER is not a bronchodilator and should not be used to treat status asthmaticus or to relieve acute asthma symptoms. Acute symptoms should be managed with an inhaled, short-acting beta-agonist, such as albuterol.

Healthcare providers should inform patients about the potential for hypersensitivity reactions, including rash, pruritus, angioedema, and anaphylactic reactions, which have been reported with ASMANEX TWISTHALER. If such reactions occur, patients should discontinue the medication immediately. Additionally, patients should be made aware that ASMANEX TWISTHALER contains small amounts of lactose, which may include trace levels of milk proteins, and that anaphylactic reactions have been reported in patients with milk protein allergy.

Patients on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and to consult their physician without delay if exposed. They should also be informed of the potential for worsening existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.

It is essential to advise patients that ASMANEX TWISTHALER may cause systemic corticosteroid effects, including hypercorticism and adrenal suppression. Patients should be informed that deaths due to adrenal insufficiency have occurred during and after transitioning from systemic corticosteroids, and they should taper slowly from systemic corticosteroids when switching to ASMANEX TWISTHALER.

Patients at increased risk for decreased bone mineral density (BMD) should be advised that the use of corticosteroids may pose an additional risk, and they should be monitored and treated appropriately for this condition. Furthermore, patients should be informed that orally inhaled corticosteroids, including mometasone furoate inhalation powder, may reduce growth velocity in pediatric patients. Physicians should closely monitor the growth of children and adolescents taking corticosteroids by any route.

Patients should be instructed to use ASMANEX TWISTHALER 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 record the date of pouch opening on the cap label and discard the inhaler 45 days after opening the foil pouch or when the dose counter reads "00," whichever comes first. The inhaler should be held upright while removing the cap, and the medication should be taken as directed, with patients breathing rapidly and deeply without exhaling through the inhaler. After each inhalation, the mouthpiece should be wiped dry, and the cap should be replaced immediately, ensuring it is rotated fully until a click is heard.

After administration, patients should rinse their mouth with water and spit out the contents without swallowing. They should store the unit as instructed. The dose counter displays the remaining doses, and when it indicates zero, the cap will lock, requiring the unit to be discarded. Patients should be advised that if the dose counter is not functioning correctly, the unit should not be used and should be brought to their physician or pharmacist for further guidance.

Storage and Handling

The product is supplied in a configuration that includes an inhaler. It should be stored in a dry place at a temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F) in accordance with USP Controlled Room Temperature guidelines.

Healthcare professionals are advised to discard the inhaler 45 days after the foil pouch has been opened or when the dose counter indicates "00," whichever occurs first. Proper adherence to these storage and handling instructions is essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)