Mometasone furoate

Mometasone furoate is the furoate ester form of mometasone (a topical synthetic glucocorticoid receptor agonist).[1] With anti-pruritic, anti-inflammatory, and vasoconstrictive properties, it is utilized to manage asthma, rhinitis, and certain skin conditions. It is formulated as a nasal spray, dry powder inhaler, and ointment for its distinct indications. [1,2]

Pharmacological Class: Corticosteroids 

• Mometasone furoate nasal spray is used to treat nasal symptoms such as congestion of allergic rhinitis in patients ≥ two years, nasal polyps in people ≥18 years, and prevention of seasonal allergic rhinitis in people ≥12 years
• Mometasone furoate ointment is indicated for symptomatic management of pruritis and dermatitis in patients ≥ two years and skin conditions like allergies, eczema, rash, and psoriasis
• Mometasone furoate inhaler is indicated for prophylaxis of asthma in patients ≥ four years [2,3] 

Mometasone furoate has a stronger glucocorticoid receptor binding affinity that is 22 times greater than dexamethasone and much greater when compared with numerous other corticosteroids. It diffuses across cell membranes and activates pathways which are responsible for reducing inflammation.

Upon administration, this corticosteroid binds to cytoplasmic glucocorticoid receptors and consequently activates glucocorticoid receptor-mediated gene expression. This stimulates phospholipase A2 inhibitory proteins, which in turn controls the release of the inflammatory precursor arachidonic acid from the phospholipid membrane via phospholipase A2.

It also alleviates inflammation by inhibiting release of transcription factors like nuclear factor kappa B (NF-kappaB) and activator-protein-1 and. In asthma, mometasone is thought to suppress lymphocytes, basophils, mast cells, and eosinophils. Evidence also indicates inhibition of cytokines, histamine, and leukotrienes. [1,2]

• For pruritis and dermatitis: Cream, 0.1% [4]
• For nasal symptoms of allergic rhinitis, nasal congestion, nasal polyps: Nasal spray 50 mcg of mometasone furoate in each 100 µl spray [5]
• For asthma: Inhalation aerosol containing 100 mcg or 200 mcg of mometasone furoate per actuation [6]

Absorption

The mean time to peak concentration is about 1.0 to 2.5 hours. The bio-availability has been noted to be as <1%. Repeated dose of inhaled corticosteroids shows a bio-availability of 11% in some studies. Therefore, the 0.1% ointment may have a bio-availability of 0.7%.

Volume of distribution

The steady-state volume of distribution is 152 L.

Protein binding

The protein binding is about 98-99% (in vitro concentration of 5 to 500ng/mL).

Metabolism

Mometasone furoate is metabolised hepatically by cytochrome P450 3A4 generating numerous metabolites such as 6-beta-hydroxy-mometasone furoate and free mometasone.

Route of elimination

About 74% is eliminated in the faeces for an inhaled dose, and 8% is eliminated in the urine.

Half-life

The terminal half-life of an inhaled dose is about five hours though it has been reported as 5.8 hours by other sources.

Clearance

The clearance rate of mometasone furoate is not readily available. However, it may be close to 90 L/h. [2]

It is contraindicated:

• In individuals with known hypersensitivity to mometasone furoate [5]
• For primary therapy of status asthmaticus or acute episodes of asthma needing intensive measures as it may deteriorate asthma [6]

Concomitant use of mometasone and strong cytochrome P450 3A4 inhibitors (such as ritonavir, telithromycin, atazanavir, nelfinavir, clarithromycin, indinavir, saquinavir, itraconazole, and nefazodone) should be avoided, as it may suppress the metabolism and systemic exposure leading to increased systemic corticosteroid adverse effects.[6]

(a) For cream:

Mometasone furoate may cause the below adverse effects:

• severe skin rash
• skin sores
• bruising or shiny skin
• small white or red bumps on the skin
• alterations in skin colour
• acne
• tiny red spots or rash around the mouth
• burning, pruritis/itching, irritation, redness, swelling, dryness, and other signs of skin infection
• skin atrophy[4,7]

(b) For nasal spray:

The most commonly occurring adverse reactions (≥5%) include:

• Epistaxis
• Headache
• Pharyngitis
• Cough
• Viral infection[5]

(c) For Inhalation Aerosol:

The most commonly adverse reactions determined in ≥ 3% of patients included:

• Sinusitis
• Nasopharyngitis
• Headache
• Influenza
• Bronchitis[6]

(a) For Cream

• It should be carefully used in pediatric patients as they may be more vulnerable to systemic toxicity
• It should be used with caution in people with visual impairment as it may increase the risk of glaucoma and cataract
• Patients applying cream should be evaluated periodically for hypothalamic-pituitary-adrenal (HPA) axis suppression. Following therapy withdrawal, reversible suppression of the HPA axis and glucocorticosteroid insufficiency might occur. Hyperglycemia and Cushing's syndrome can occur due to systemic absorption.[4]

(b) For Nasal spray

• Avoid use in people with recent nasal trauma, nasal ulcers, or nasal surgery as it may cause adverse effects on the nasal mucosa such as nasal septal perforation, epistaxis, Candida albicans infection, nasal ulceration, and impaired wound healing.
• It is associated with the risk of ophthalmic adverse reactions such as cataracts and glaucoma. Thus it should be used with caution
• It can aggravate the risk of infections such as tuberculosis, viral, fungal, parasitic, or bacterial infections; ocular herpes simplex; chickenpox or measles; thus, it should be used cautiously in patients with existing infections
• It can considerably reduce the growth velocity in children, thus should be used with caution
• It should be used prudently as it may cause adrenal suppression and hypercorticism [5]

(c) Inhalation Aerosol

• It should be used vigilantly in people with infections (chickenpox; tuberculosis; bacterial, viral, parasitic, or fungal infection; ocular herpes simplex; measles) as it may deteriorate the existing infections
• Monitor use in pediatric patients as it may retard the growth
• Monitor use in people with significant risk factors for reduced bone mineral content as this corticosteroid is linked with a decrease in bone mineral density
• It should be used with caution in people having a history of raised intraocular pressure, glaucoma, cataracts, and people at risk of hypersensitivity reactions, paradoxical bronchospasm, hypercorticism, and adrenal suppression
• Monitor people for signs of noxious effects on the oral cavity since it may increase the risk of Candida albicans infection of the throat and mouth [6]

(a) Mometasone furoate for management of dermatitis and other skin diseases

Compared to the control cream, 0.1% mometasone furoate cream was found to prevent the occurrence of moderate-to-severe acute radiation dermatitis in 124 breast cancer people receiving postmastectomy radiation in a double-blinded randomized trial.[8] A review by Fabrizio Spada et al. reported higher efficacy of mometasone furoate with a low risk of both local and systemic side effects for combating eczema, psoriasis, and seborrhoeic dermatitis.[9]

The local application of mometasone furoate was reported to prevent acute radiation dermatitis in people with head and neck squamous cell carcinomas in a randomized, self-controlled, prospective analysis. [10]

(b) Mometasone furoate for management of rhinitis

A systematic review by Desiderio Passali et al. demonstrated that mometasone furoate nasal spray effectively combat inflammatory diseases of the nose, seasonal and perennial allergic rhinitis, paranasal sinuses, and rhinosinusitis. [11] In a randomized, prospective, double-blinded, placebo-controlled trial of 64 patients, Mometasone furoate -impregnated biodegradable nasal dressings improve the endoscopic appearance in the healing process of chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery. [12]

(c) Mometasone furoate for management of asthma

In a 12-week, placebo-controlled, double-blind, double-dummy trial, all the three doses of mometasone furoate (50, 100, and 200 mcg two times a day) were well-tolerated and found to substantially improve forced expiratory volume in one second (FEV1) after 12 weeks of therapy in children aged 5-11 years suffering from persistent asthma.[13]

1. Mometasone furoate. PubChem Compound Summary. CID 441336. Available online from: https://pubchem.ncbi.nlm.nih.gov/compound/Mometasone-furoate [Last accessed on: 8 July 2021]
2. Mometasone furoate. Drug Bank. Accession Number: DB14512. Available online from: https://go.drugbank.com/drugs/DB14512. [Last accessed on: 8 July 2021]
3. Mometasone FUROATE Ointment. Available from: https://www.webmd.com/drugs/2/drug-5904/mometasone-topical/details [Last accessed on: 8 July 2021]
4. ELOCON® (mometasone furoate) Cream. FDA Label. Available online from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019625s026lbl.pdf. [Last accessed on: 8 July 2021]
5. NASONEX® (mometasone furoate monohydrate) Nasal Spray. FDA Label. Available online from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020762s053lbl.pdf. [Last accessed on: 8 July 2021]
6. ASMANEX® HFA (mometasone furoate) Inhalation Aerosol. FDA Label. Available online from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205641s000lbl.pdf. [Last accessed on: 8 July 2021]
7. Mometasone Topical. MedlinePlus. Available online from: https://medlineplus.gov/druginfo/meds/a687014.html. [Last accessed on: 8 July 2021]
8. Ho AY, Olm-Shipman M, Zhang Z, Siu CT, Wilgucki M, Phung A et al. A randomized trial of mometasone furoate 0.1% to reduce high-grade acute radiation dermatitis in breast cancer patients receiving postmastectomy radiation. International Journal of Radiation Oncology Biology Physics. 2018 Jun 1;101(2):325-33.
9. Spada F, Barnes TM, Greive KA. Comparative safety and efficacy of topical mometasone furoate with other topical corticosteroids. Australasian Journal of Dermatology. 2018 Aug;59(3):e168-74.
10. Liao Y, Feng G, Dai T, Long F, Tang J, Pu Y et al. Randomized, self-controlled, prospective assessment of the efficacy of mometasone furoate local application in reducing acute radiation dermatitis in patients with head and neck squamous cell carcinomas. Medicine. 2019 Dec;98(52).
11. Passali D, Spinosi MC, Crisanti A, Bellussi LM. Mometasone furoate nasal spray: a systematic review. Multidisciplinary respiratory medicine. 2016 Dec;11(1):1-5.
12. Zhao KQ, Yu YQ, Yu HM. Effects of mometasone furoate–impregnated biodegradable nasal dressing on endoscopic appearance in the healing process following endoscopic sinus surgery: a randomized, double‐blind, placebo‐controlled study. InInternational forum of allergy & rhinology. 2018 Nov;8(11):1233-1241.
13. Amar NJ, Shekar T, Varnell TA, Mehta A, Philip G. Mometasone furoate (MF) improves lung function in pediatric asthma: a double‐blind, randomized controlled dose‐ranging trial of MF metered‐dose inhaler. Pediatric pulmonology. 2017 Mar;52(3):310-8.