Mometasone

Mometasone is a synthetic corticosteroids.

Mometasone is used in treating Asthma. It is also used to treat Perennial allergic rhinitis, Seasonal allergic rhinitis, Corticosteroid-responsive dermatoses.

The onset of action of Mometasone was ≥1 to 2 weeks

The Duration of time for Mometasone was Several days or more

Mometasone shows common side effects like burning, stinging, increased nasal discharge, dryness inside the nose, sneezing, nervousness, nausea, dizziness.

Mometasone is available in the form of nasal spray, nasal drops, eye drops and topical cream.

Mometasone is available in India, Germany, Canada, Italy, USA

Mometasone is a synthetic corticosteroid that has local anti-inflammatory, antipruritic, and vasoconstrictive properties. It may inhibit the formation, release, and activity of endogenous chemical mediators of inflammation (kinins, liposomal enzymes, histamine, prostaglandins) by inducing phospholipase A₂ inhibitory proteins and sequential blocking of arachidonic acid release. Furthermore, it inhibits the margination and subsequent cell migration to the injury site; it reverses vascular dilatation and increases vessel permeability, resulting in reduced access of cells to the areas of injury.

Mometasone is available in the form of nasal spray, nasal drops, eye drops and topical cream.

Mometasone is used in treating Asthma. It is also used to treat Perennial allergic rhinitis, Seasonal allergic rhinitis, Corticosteroid-responsive dermatoses.

May depress the formation, release, and activity of endogenous chemical mediators of inflammation (kinins, histamine, liposomal enzymes, prostaglandins). Leukocytes and macrophages may have to be present for the initiation of responses mediated by the above substances. Inhibits the margination and subsequent cell migration to the area of injury, and also reverses the dilatation and increased vessel permeability in the area resulting in decreased access of cells to the sites of injury.

Mometasone is approved for use in the following clinical indications

Asthma: Maintenance treatment of asthma as prophylactic therapy in patients ≥4 years of age.

Although not approved there have been certain off-label uses documented for Mometasone which includes

Perennial allergic rhinitis, Seasonal allergic rhinitis, Corticosteroid-responsive dermatoses.

Adult: As 50 mcg/actuation nasal spray: Initially, 2 actuations (100 mcg) in each nostril once daily (total dose: 200 mcg), may be increased after 5-6 weeks to 2 actuations (100 mcg) in each nostril bid (total dose: 400 mcg daily) if symptoms are inadequately controlled. Titrate to the lowest effective dose. If there is no improvement after 5-6 weeks of bid administration, re-evaluate patient and reconsider treatment strategy.

Mometasone is available in various strengths as

creams/ointments:0.5%, 0.1%.

Inhalation: 100 or 200 mcg per actuation.

Mometasone is available in the form of spray, inhaler, cream, ointment.

Dosage Adjustment for Pediatric Patients:

• Asthma: Note: Asmanex Twisthaler (110 mcg and 220 mcg Twisthaler) deliver 100 and 200 mcg mometasone furoate per actuation respectively; NAEPP uses doses based on delivery dose, while manufacturer recommended doses are based on inhaler amount. Maximum effects may not be evident for 1 to 2 weeks or longer; higher doses may provide additional asthma control in patients who do not respond adequately after 2 weeks of therapy. Doses should be titrated to the lowest effective dose once asthma is controlled.

Maintenance therapy:

• AsmanexTwisthaler (dry powder inhaler):

Children 4 to 11 years (regardless of prior therapy): Note: Use 110 mcg inhaler: Oral inhalation (110 mcg/inhalation): Initial: 110 mcg once daily, administered in the evening. Maximum daily dose: 110 mcg/day.

Children ≥12 years and Adolescents: Dosing based on previous asthma therapy:

Patients previously treated with bronchodilators alone or with inhaled corticosteroids: Oral inhalation (220 mcg/inhalation): Initial: 220 mcg once daily, administered in the evening; may increase dose after 2 weeks if adequate response not obtained. Maximum daily dose: 440 mcg/day; may be administered as 1 inhalation twice daily or 2 inhalations once daily in the evening.

Patients previously treated with oral corticosteroids: Oral inhalation (220 mcg/inhalation): Initial: 440 mcg twice daily. Maximum daily dose: 880 mcg/day.

• Asmanex HFA:

Children 5 to <12 years: Oral inhalation (50 mcg/inhalation): 100 mcg twice daily; maximum daily dose: 200 mcg/day.

Children ≥12 years and Adolescents: Note: Dosing based on previous asthma therapy:

Patients previously treated with inhaled medium dose corticosteroid: Oral inhalation (100 mcg/inhalation): 200 mcg twice daily; maximum daily dose: 800 mcg/day.

Patients previously treated with high-dose inhaled corticosteroids or oral corticosteroids: Oral inhalation (200 mcg/inhalation): 400 mcg twice daily; maximum daily dose: 800 mcg/day.

• Asthma guidelines:

Global Initiative for Asthma Guidelines Dry powder inhaler:

Children 6 to 11 years: Oral inhalation:

“Low” dose: 110 mcg/day.

“Medium” dose: ≥220 to <440 mcg/day.

“High” dose: ≥440 mcg/day.

Children ≥12 years and Adolescents: Oral inhalation:

“Low” dose: 110 to 220 mcg/day.

“Medium” dose: >220 to 440 mcg/day.

“High” dose: >440 mcg/day.

• National Asthma Education and Prevention Program: Dry powder inhaler: Children ≥12 years and Adolescents: Oral inhalation:

"Low" dose: 200 mcg/day.

"Medium" dose: 400 mcg/day.

"High" dose: >400 mcg/day.

Mild flare, exacerbation: Limited data available:

Children ≥12 years and Adolescents with mild to moderate asthma, no prior history of life-threatening asthma exacerbations, and with good self-management skills:

It is recommended to temporarily quadruple the inhaled corticosteroid dose early in the course of a mild flare to decrease the severity of an asthma exacerbation. After symptoms stabilize or after a maximum of 14 days of quadrupled dose, whichever occurs first, patients should be returned to their baseline dose. Quadrupling the inhaled corticosteroid dose has been shown to decrease the severity of an asthma exacerbation in select patients. In a randomized trial of adolescents ≥16 years and adults (n=1,871), temporarily quadrupling the inhaled corticosteroid dose when asthma control began to deteriorate resulted in fewer severe asthma exacerbations (ie, less treatment with systemic glucocorticoids or unscheduled appointments for asthma) compared to patients who maintained their inhaled corticosteroid dose. No data for quadrupling the dose in patients <16 years of age has been published. Quintupling the dose of inhaled corticosteroids (fluticasone) in children 5 to 11 years of age was not shown to reduce the rate of severe exacerbations and may have been associated with adverse effects (decreased linear growth, particularly in patients <8 years of age) .

Conversion from oral systemic corticosteroids to orally-inhaled corticosteroids: When using mometasone oral inhalation to help reduce or discontinue oral corticosteroid therapy, begin prednisone taper after at least 1 week of mometasone inhalation therapy; prednisone should be tapered slowly (ie, no faster than 2.5 mg/day on a weekly basis); monitor patients for signs of asthma instability and adrenal insufficiency; decrease mometasone to lowest effective dose after prednisone reduction is complete.

• Hypersensitivity to mometasone or any component of the formulation; hypersensitivity to milk proteins (AsmanexTwisthaler only); primary treatment of status asthmaticus or other acute episodes of asthma for which intensive measures are required

• Documentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections (particularly gastroenteritis), or other conditions with severe electrolyte loss. Select surgical patients on long-term, high-dose, inhaled corticosteroids should be given stress doses of hydrocortisone intravenously during the surgical period and the dose reduced rapidly within 24 hours after surgery.

• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; reaction should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue mometasone and institute alternative therapy.

• Hypersensitivity: Hypersensitivity reactions (eg, allergic dermatitis, anaphylaxis, angioedema, bronchospasm, flushing, pruritus, rash, urticaria) may occur; discontinue use if reaction occurs.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use if possible in patients with ocular herpes; active or quiescent respiratory tuberculosis; or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intravenous immunoglobulin, respectively, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

• Oral candidiasis: Local oropharyngeal Candida infections have been reported; if this occurs, treat appropriately while continuing therapy. Patients should be instructed to rinse mouth with water (without swallowing) and spit after each use.

Pregnancy Category C: Teratogenicity studies have been performed in animals.

• Common Adverse effects:

Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, hyperglycaemia, glycosuria, growth retardation in children and adolescents, decreased BMD, cataracts, glaucoma

• Less Common Adverse effects:

Visual disturbances (e.g. Blurred vision), immunosuppression; hypersensitivity reactions (e.g. Anaphylaxis, angioedema, pruritus, rash, urticaria, wheezing); local nasal effects such as nasal septum perforation, epistaxis, nasal irritation, and infection of the nose and/or pharynx (nasal); oropharyngeal candidiasis (inhalation)

• Rare Common Adverse effects:

Throat irritation, disturbance of taste (nasal).

Strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, cobicistat-containing products) may increase the systemic exposure of mometasone, potentially increasing the risk for systemic corticosteroid adverse effects.

The common side effects of Mometasone include the following throat irritation, disturbance of taste (nasal).

Symptoms: Suppression of pituitary-adrenal function resulting in secondary adrenal insufficiency.

Management: Symptomatic treatment. If electrolyte imbalance occurs, treat it as necessary. For chronic toxicity, slowly withdraw corticosteroid use.

Pharmacodynamic

Mometasone is a synthetic corticosteroid that has local anti-inflammatory, antipruritic, and vasoconstrictive properties. It may inhibit the formation, release, and activity of endogenous chemical mediators of inflammation (kinins, liposomal enzymes, histamine, prostaglandins) by inducing phospholipase A₂ inhibitory proteins and sequential blocking of arachidonic acid release. Furthermore, it inhibits the margination and subsequent cell migration to the injury site; it reverses vascular dilatation and increases vessel permeability, resulting in reduced access of cells to the areas of injury.

Pharmacokinetics

• Absorption: Poorly absorbed following inhalation, nasal use, and topical application. Bioavailability: <1%.
• Distribution: Plasma protein binding: 98-99%.
• Metabolism: Extensively metabolised in the liver mainly by the CYP3A4 isoenzyme to multiple metabolites.
• Excretion: Mainly via faeces (approx 74%); urine (approx 8%). Elimination half-life: Approx 5 hours.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Mometasone ?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/