Mometasone furoate

Uses and Indications

Mometasone furoate is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients aged 2 years and older. This indication applies to various formulations, including cream, ointment, and lotion.

Asthma Management ASMANEX HFA and ASMANEX TWISTHALER are indicated for the maintenance treatment of asthma as prophylactic therapy in patients aged 5 years and older and 4 years and older, respectively. Both formulations are not indicated for the relief of acute bronchospasm.

Chronic Rhinosinusitis SINUVA Sinus Implant is indicated for the treatment of chronic rhinosinusitis with nasal polyps in adult patients aged 18 years and older who have undergone ethmoid sinus surgery. Additionally, mometasone furoate nasal spray is indicated for the prophylaxis of nasal symptoms of seasonal allergic rhinitis in patients aged 12 years and older and for the treatment of chronic rhinosinusitis with nasal polyps in adult patients aged 18 years and older.

Limitations of Use ASMANEX HFA and ASMANEX TWISTHALER are not indicated for the relief of acute bronchospasm. Mometasone furoate topical solution (lotion) is indicated for patients aged 12 years and older, while other formulations are indicated for patients aged 2 years and older.

Dosage and Administration

For Mometasone Furoate, the recommended administration varies by formulation. A thin film of cream, ointment, or lotion should be applied to the affected skin areas once daily. For the solution, a few drops should be applied to the affected areas once daily, massaging lightly until absorbed. Therapy should be discontinued once control is achieved. If no improvement is observed within 2 weeks, the diagnosis should be reassessed. The use of occlusive dressings is not recommended unless directed by a physician.

For Asmanex HFA, the aerosol formulation is intended for oral inhalation only. In patients aged 12 years and older, the recommended dosage is 2 inhalations twice daily of either 100 mcg or 200 mcg, with the starting dosage based on prior asthma therapy. For patients aged 5 to less than 12 years, the recommended dosage is 2 inhalations twice daily of 50 mcg.

For Asmanex Twisthaler, the recommended starting dose for patients aged 12 years and older who have previously received bronchodilators alone or inhaled corticosteroids is 220 mcg once daily in the evening, with a maximum daily dose of 440 mcg. For those who have received oral corticosteroids, the starting dose is 440 mcg twice daily, with a maximum of 880 mcg. For children aged 4 to 11 years, the starting dose is 110 mcg once daily in the evening, with a maximum of 110 mcg.

The Sinuva Sinus Implant is to be placed in the ethmoid sinus under endoscopic visualization by a physician trained in otolaryngology. The implant is designed to gradually release corticosteroid over a period of 90 days and should be removed by 90 days or earlier at the physician's discretion using standard surgical instruments.

For the metered spray formulation of Mometasone Furoate, the recommended dosage for the prophylaxis of seasonal allergic rhinitis in adults and pediatric patients aged 12 years and older is 2 sprays in each nostril once daily. For the treatment of chronic rhinosinusitis with nasal polyps in adults (18 years and older), the recommended dosage is 2 sprays in each nostril twice daily, although 2 sprays once daily may also be effective for some patients. The route of administration is nasal use only.

Contraindications

Mometasone furoate in any formulation is contraindicated in patients with a history of hypersensitivity to any of the components in the preparation.

Asmanex HFA and Asmanex are contraindicated for the primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures. Additionally, patients with known hypersensitivity to milk proteins or any ingredients of Asmanex Twisthaler should not use this medication.

Sinuva is contraindicated in patients with known hypersensitivity to mometasone furoate or any of the ingredients of the Sinuva Sinus Implant.

Warnings and Precautions

Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment, Cushing’s syndrome, and hyperglycemia may occur due to systemic absorption of mometasone furoate. Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. Use should be modified should HPA axis suppression develop. Pediatric patients may be more susceptible to systemic toxicity.

Serious Warnings

ASMANEX HFA and ASMANEX TWISTHALER should not be used for the relief of acute asthma symptoms. Patients experiencing rapidly deteriorating asthma require immediate re-evaluation. Paradoxical bronchospasm may occur; if this happens, ASMANEX should be discontinued and alternative therapy instituted.

Monitoring Requirements

Patients using ASMANEX should be monitored for localized infections, particularly Candida albicans infections of the mouth and throat. It is advised that patients rinse their mouth with water and spit out the contents after dosing. Additionally, patients with major risk factors for decreased bone mineral density should be monitored, as well as the growth of pediatric patients receiving ASMANEX.

Ocular Effects

Both mometasone furoate and ASMANEX may increase the risk of cataracts and glaucoma. If visual symptoms occur, referral to an ophthalmologist should be considered. Patients with a history of increased intraocular pressure, glaucoma, or cataracts should be monitored closely.

Infection Risks

There is a potential for worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, as well as ocular herpes simplex infections. More serious or even fatal courses of chickenpox or measles can occur in susceptible patients. Caution is advised in patients with these infections due to the potential for worsening.

Adrenal Function

When transferring patients from systemic corticosteroids to ASMANEX, there is a risk of impaired adrenal function. Patients should be weaned slowly from systemic corticosteroids. Hypercorticism and adrenal suppression may occur with very high dosages or at regular dosages in susceptible individuals; if such changes occur, ASMANEX should be discontinued slowly.

Hypersensitivity Reactions

Hypersensitivity reactions, including urticaria, flushing, allergic dermatitis, bronchospasm, rash, pruritus, angioedema, and anaphylaxis, may occur with the use of ASMANEX. Discontinue ASMANEX if such reactions occur.

Nasal Effects

For patients using mometasone furoate nasal spray, monitor for epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, and impaired wound healing. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma.

Growth Suppression

Long-term use of mometasone furoate may lead to a reduction in growth velocity in children. Routine monitoring of growth is recommended for pediatric patients receiving mometasone furoate.

Side Effects

Patients using Mometasone Furoate in various formulations (cream, ointment, lotion, and nasal spray) may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common Adverse Reactions

• Topical Formulations (Cream, Ointment, Lotion):

  • Burning

  • Pruritus

  • Skin atrophy

  • Tingling/stinging

  • Acneiform reaction

  • Folliculitis

  • Furunculosis

• Nasal Spray:

  • Headache

  • Viral infection

  • Pharyngitis

  • Epistaxis

  • Cough

• Inhaled Formulations (Asmanex HFA and Asmanex):

  • Nasopharyngitis

  • Headache

  • Sinusitis

  • Bronchitis

  • Influenza

  • Oral candidiasis

  • Dysmenorrhea

  • Musculoskeletal pain

  • Back pain

  • Dyspepsia

Serious Adverse Reactions

• Hypersensitivity Reactions: Including anaphylaxis, angioedema, rash, pruritus, and bronchospasm. Discontinue use if such reactions occur.

• Deterioration of Asthma: Patients should not use Mometasone for acute symptom relief and require immediate re-evaluation during rapidly deteriorating asthma.

• Infections: Potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections; ocular herpes simplex infections; and more serious or fatal courses of chickenpox or measles in susceptible patients.

• Adrenal Suppression: Risk of impaired adrenal function when transitioning from systemic corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to Mometasone.

• Hypercorticism: May occur with high dosages or in susceptible individuals. Discontinue slowly if such changes occur.

• Bone Mineral Density Reduction: Long-term administration may lead to decreased bone mineral density; monitor patients with major risk factors.

• Growth Suppression in Pediatric Patients: Monitor growth routinely in pediatric patients receiving Mometasone.

Pediatric Use

• Pediatric patients are at a greater risk of HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension when treated with topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Intracranial hypertension may present as bulging fontanelles, headaches, and bilateral papilledema.

Additional Considerations

• Cataracts and Glaucoma: Long-term use may increase the risk; consider referral to an ophthalmologist if visual symptoms occur.

• Systemic Absorption: Topically applied Mometasone can be absorbed in sufficient amounts to produce systemic effects, including hyperglycemia.

• Contraindications: Mometasone is contraindicated in patients with a history of hypersensitivity to any of its components.

Patients should be monitored for these adverse reactions, and any significant changes in health status should prompt a reevaluation of treatment.

Drug Interactions

Concomitant use of mometasone furoate formulations with strong cytochrome P450 3A4 inhibitors, such as ritonavir and ketoconazole, should be approached with caution. These inhibitors may increase systemic exposure to mometasone furoate, potentially leading to enhanced systemic corticosteroid effects.

Mometasone Furoate Formulations

• Cream, Ointment, Lotion, Solution: No formal drug-drug interaction studies have been conducted with any mometasone furoate topical formulations. Additionally, no specific drug interactions or laboratory test interactions have been reported for these forms.

• Nasal Spray: While no formal drug-drug interaction studies have been conducted, in vitro studies indicate that mometasone furoate is primarily metabolized by CYP3A4. Co-administration with CYP3A4 inhibitors may inhibit its metabolism, increasing systemic exposure and the risk of systemic corticosteroid side effects. Caution is advised when considering the use of mometasone furoate nasal spray alongside long-term treatment with strong CYP3A4 inhibitors.

Sinuva Sinus Implant

The SINUVA Sinus Implant has not undergone formal drug-drug interaction studies. However, concurrent administration with ketoconazole, a potent CYP3A4 inhibitor, may elevate plasma concentrations of mometasone furoate.

In summary, while many mometasone furoate formulations lack specific interaction studies, the potential for increased systemic effects when used with CYP3A4 inhibitors necessitates careful consideration and monitoring.

Pediatric Use

Mometasone furoate may be used with caution in pediatric patients aged 2 years and older. However, the safety and efficacy of its use for longer than 3 weeks have not been established, and its use is not recommended in patients below 2 years of age. In clinical trials involving pediatric patients with atopic dermatitis, the majority of subjects aged 2 to 12 years treated with mometasone furoate cream once daily cleared within 3 weeks.

Efficacy and Safety

• Mometasone furoate cream caused HPA axis suppression in approximately 16% of pediatric subjects aged 6 to 23 months, while ointment formulations showed suppression in about 27% of the same age group. The treatment duration was approximately 3 weeks, with a mean body surface area treated of 39% to 41%.

• Pediatric patients are at a greater risk than adults for HPA axis suppression and Cushing's syndrome due to a higher ratio of skin surface area to body mass. They may also be more susceptible to skin atrophy, including striae, when treated with topical corticosteroids.

• HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression include low plasma cortisol levels and an absence of response to ACTH stimulation, while signs of intracranial hypertension may include bulging fontanelles, headaches, and bilateral papilledema.

Dosing Considerations

• Pediatric patients applying topical corticosteroids to more than 20% of body surface area are at higher risk of HPA axis suppression. Long-term use of topical corticosteroids has not been studied in this population, and caution is advised.

• For inhaled corticosteroids, including ASMANEX HFA and ASMANEX TWISTHALER, safety and effectiveness have been established in patients aged 5 years and older, with a noted mean reduction in growth velocity of approximately 1 cm per year. The long-term effects on final adult height remain unknown, and growth should be monitored routinely.

Special Populations

• The safety and effectiveness of mometasone furoate nasal spray for chronic rhinosinusitis with nasal polyps in pediatric patients less than 18 years of age have not been established. In a trial involving patients aged 6 to 17 years, effectiveness was not demonstrated.

• Pediatric patients receiving nasal corticosteroids should also have their growth monitored, as nasal corticosteroids may cause a reduction in growth velocity.

Mometasone furoate should not be used in the treatment of diaper dermatitis.

Geriatric Use

Clinical studies involving mometasone furoate formulations, including cream, ointment, and inhalants, have included a significant number of geriatric patients, specifically those aged 65 years and older. For instance, trials for mometasone furoate cream included 190 subjects aged 65 and over, while ointment studies involved 310 subjects in the same age group. In these studies, no overall differences in safety or effectiveness were observed between geriatric patients and younger subjects. However, it is important to note that greater sensitivity in some older individuals cannot be ruled out.

For ASMANEX HFA and ASMANEX TWISTHALER, clinical trials included 38 and 175 patients aged 65 and older, respectively, with similar findings regarding safety and effectiveness. No dosage adjustments are warranted for geriatric patients based on the available data for ASMANEX HFA.

In general, for formulations of mometasone furoate that did not include sufficient numbers of subjects aged 65 and over, clinical experience has not identified significant differences in responses between elderly and younger patients. Nevertheless, it is recommended that dose selection for elderly patients be approached with caution, typically starting at the lower end of the dosing range to account for potential increased sensitivity.

Overall, while geriatric patients have been included in clinical trials for these medications, careful monitoring and consideration of individual patient factors are advised when prescribing to this population.

Pregnancy

There are no adequate and well-controlled studies of mometasone furoate in pregnant women. Mometasone furoate is classified as Pregnancy Category C, indicating that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids, including mometasone furoate, have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels, and some have demonstrated teratogenic effects following dermal application.

In animal reproduction studies, mometasone furoate has been associated with increased fetal malformations and decreased fetal survival and growth in pregnant mice, rats, and rabbits. The doses that produced these adverse effects were approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m² or AUC basis. Specific findings include:

• In mice, cleft palate was observed at subcutaneous doses of 60 mcg/kg and above, with reduced fetal survival at 180 mcg/kg. No toxicity was noted at 20 mcg/kg.

• In rats, topical doses of 600 mcg/kg and above resulted in umbilical hernias, while a dose of 300 mcg/kg caused delays in ossification without malformations.

• In rabbits, multiple malformations such as flexed front paws, gallbladder agenesis, umbilical hernia, and hydrocephaly were noted at topical doses of 150 mcg/kg and above. Oral administration at 700 mcg/kg led to increased resorptions and cleft palate or head malformations, with most litters aborted or resorbed at 2800 mcg/kg. No toxicity was observed at 140 mcg/kg.

Additionally, when administered to pregnant rats throughout pregnancy or during late gestation, doses of 15 mcg/kg resulted in prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival. Similar effects were not observed at 7.5 mcg/kg.

In women with poorly or moderately controlled asthma, there is an increased risk of perinatal adverse outcomes, including preeclampsia, prematurity, low birth weight, and small for gestational age neonates. Therefore, pregnant women with asthma should be closely monitored, and medication should be adjusted as necessary to maintain optimal asthma control.

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. Given the potential risks associated with corticosteroid use during pregnancy, healthcare providers should carefully weigh the benefits against the risks when considering treatment options for pregnant patients.

Lactation

Systemically administered corticosteroids, including mometasone furoate, are known to appear in human milk and may potentially suppress growth, interfere with endogenous corticosteroid production, or cause other adverse effects in breastfed infants. While it is unclear whether topical administration of mometasone furoate (in forms such as cream, ointment, lotion, or solution) results in sufficient systemic absorption to produce detectable quantities in human milk, caution is advised when these products are used by lactating mothers.

There is limited data regarding the presence of inhaled corticosteroids, such as ASMANEX HFA and ASMANEX TWISTHALER, in human milk, as well as their effects on breastfed children or milk production. However, similar inhaled corticosteroids have been detected in human milk. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for these medications and any potential adverse effects on the breastfed infant.

For mometasone furoate nasal spray, systemic absorption is minimal, and breastfeeding is not expected to expose the infant to significant amounts of the drug. Nonetheless, the mother's clinical need for the nasal spray and any potential risks to the breastfed infant should be carefully considered.

In summary, while the safety of mometasone furoate and other corticosteroids during lactation is not fully established, healthcare providers should exercise caution and consider both the benefits of breastfeeding and the mother's treatment needs when advising lactating mothers.

Renal Impairment

Patients with renal impairment do not have specific dosage adjustments, monitoring requirements, or safety considerations outlined for the use of Mometasone Furoate in its various formulations, including cream, ointment, lotion, solution, and aerosol. The available data across multiple labels indicates a lack of information regarding the impact of reduced kidney function on the pharmacokinetics or safety profile of these products. Consequently, healthcare providers should exercise caution and consider individual patient circumstances when prescribing Mometasone Furoate to patients with renal impairment, as the absence of specific guidance necessitates a careful assessment of potential risks and benefits.

Hepatic Impairment

Patients with hepatic impairment may experience increased concentrations of mometasone furoate, particularly with more severe liver dysfunction. However, there is no specific information provided regarding dosage adjustments, special monitoring, or precautions for patients with liver problems across various formulations, including cream, ointment, lotion, aerosol, inhalant, solution, and implant forms of mometasone furoate.

It is advisable for healthcare providers to consider the potential for altered pharmacokinetics in patients with hepatic impairment and to monitor these patients closely for any adverse effects or therapeutic efficacy.

Overdosage

Topically applied mometasone furoate, available in various forms such as cream, ointment, lotion, and solution, can be absorbed in sufficient amounts to produce systemic effects. While acute overdose is unlikely to require any treatment beyond observation due to low systemic bioavailability, chronic overdosage may lead to signs and symptoms of hypercorticism.

In clinical studies, single oral doses of up to 8000 mcg of mometasone furoate have been administered to adult subjects without any reported adverse reactions. However, it is important to monitor for potential symptoms of hypercorticism in cases of chronic overdosage.

For any suspected overdose, healthcare professionals are advised to observe the patient closely and manage symptoms as they arise. There are no specific data available regarding the effects of acute or chronic overdosage with certain formulations, such as the Sinuva Sinus Implant and mometasone furoate nasal spray, but the general recommendation remains to monitor the patient and provide supportive care as needed.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of mometasone furoate in its various formulations. However, long-term carcinogenicity studies conducted via inhalation in Sprague Dawley rats and Swiss CD-1 mice demonstrated no statistically significant increase in tumor incidence. In a 2-year study involving rats, mometasone furoate was administered at inhalation doses up to 67 mcg/kg, which is approximately 0.04 times the estimated maximum clinical topical dose. Similarly, a 19-month study in mice at doses up to 160 mcg/kg (approximately 0.05 times the estimated maximum clinical topical dose) also showed no significant tumor increase.

Mometasone furoate exhibited increased 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 found to be mutagenic in the Ames test or the mouse lymphoma assay, nor was it clastogenic in various in vivo assays, including the mouse micronucleus assay and the rat bone marrow 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 in either male or female subjects at subcutaneous doses up to 15 mcg/kg, which is approximately 0.01 times the estimated maximum clinical topical dose.

Teratogenic Effects

Mometasone furoate has been shown to have teratogenic effects in laboratory animals. In mice, subcutaneous doses of 60 mcg/kg and above resulted in cleft palate, while fetal survival was reduced at 180 mcg/kg. In rabbits, multiple malformations, including flexed front paws, gallbladder agenesis, umbilical hernia, and hydrocephaly, were observed at topical dermal doses of 150 mcg/kg and above. An oral study indicated that at 700 mcg/kg, mometasone furoate increased resorptions and caused cleft palate and/or head malformations, with most litters being aborted or resorbed at 2800 mcg/kg.

In rats, topical doses of 600 mcg/kg and above produced umbilical hernias, while a dose of 300 mcg/kg resulted in delays in ossification without malformations. Furthermore, when administered throughout pregnancy, a subcutaneous dose of 15 mcg/kg caused prolonged and difficult labor, reduced the number of live births, and decreased birth weight and early pup survival. No adverse effects were noted at a dose of 7.5 mcg/kg.

Given these findings, mometasone furoate should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.

Storage and Handling

Mometasone Furoate is available in various formulations, including cream, ointment, lotion, solution, and aerosol. The specific storage conditions and handling requirements for each formulation are as follows:

Cream

• Mometasone Furoate Cream is supplied in tubes and should be stored at 25°C (77°F), with excursions permitted between 15° to 30°C (59° to 86°F). It is important to avoid excessive heat.

Ointment

• Mometasone Furoate Ointment is available in 15-gram and 45-gram tubes. It should be stored at 25°C (77°F), with excursions permitted between 15° to 30°C (59° to 86°F). Refrigeration and freezing should be avoided.

Lotion

• Mometasone Furoate Lotion, 0.1%, is supplied in 30-mL (27.5 gram) and 60-mL (55 gram) bottles. It should be stored at 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F).

Solution

• Mometasone Furoate Topical Solution, 0.1%, should be stored at 20° to 25°C (68° to 77°F), with excursions permitted between 15° to 30°C (59° to 86°F).

Aerosol

• Asmanex HFA aerosol should be stored at controlled room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F). After priming, the inhaler should be stored with the mouthpiece down or in a horizontal position. It is crucial to keep the canister at room temperature before use, shake well before use, and avoid exposure to heat or open flame. The inhaler should be discarded when the labeled number of actuations has been used.

General Handling

• All formulations should be kept out of reach of children. Care should be taken to avoid spraying in the eyes, and containers under pressure should not be punctured or exposed to temperatures above 120°F, as this may cause bursting. Containers should never be thrown into fire or incinerated.

These storage and handling guidelines ensure the integrity and efficacy of Mometasone Furoate products.