Mometasone furoate

Mometasone furoate
Systematic (IUPAC) name
(11β,16α)-9,21-dichloro-11-hydroxy-16-methyl-3,20-dioxopregna-1,4-dien-17-yl 2-furoate
Clinical data
Trade names Asmanex Twisthaler, Ecural mometAid, Elocon, Elocom, Elomet, Elosalic, Nasonex, Novasone
AHFS/Drugs.com monograph
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Topical, inhalation
Legal status
Legal status
Pharmacokinetic data
Bioavailability Nasal spray is virtually undetectable in plasma; but systemic availability is comparable to fluticasone[1]
Protein binding 98% to 99%
Metabolism Hepatic
Biological half-life 5.8 hours
Identifiers
CAS Number 105102-22-5 YesY 83919-23-7
ATC code D07AC13 (WHO) R01AD09, R03BA07
PubChem CID 441336
DrugBank DB00764 N
ChemSpider 390091 YesY
ChEBI CHEBI:47564 YesY
ChEMBL CHEMBL1161 YesY
Synonyms (9R,10S,11S,13S,14S,16R,17R)-9-chloro-17-(2-chloroacetyl)-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl furan-2-carboxylate
Chemical data
Formula C22H28Cl2O4 for Mometasone
C27H30O6Cl2 as Furoate
Molar mass 427.361 g/mol (Mometasone)
521.4 g/mol (Furoate)
 NYesY (what is this?)  (verify)

Mometasone furoate is a glucocorticosteroid used topically to reduce inflammation of the skin or in the airways. It is a prodrug of the free form mometasone (INN).

Uses

Mometasone furoate is used in the treatment of inflammatory skin disorders (such as eczema and psoriasis) (topical form), allergic rhinitis (such as hay fever) (topical form), asthma (inhalation form)[2][3] for patients unresponsive to less potent corticosteroids, and penile phimosis.[4] In terms of steroid strength, it is more potent than hydrocortisone, and less potent than dexamethasone.[5]

There is some low quality evidence suggesting the use of mometasone for symptomatic improvement in children with adenoid hypertrophy.[6]

Mometasone is indicated for the alleviation of inflammatory and pruritic manifestations (with stinging and itching) of dermatosis which respond to treatment with glucocorticoides such as psoriasis and atopic dermatitis (affection dermic chronic, characterized by the apparition of squamous eruptions, accompanied by itching).

Nasal mometasone is employed in adults (including the elderly) and children over 2 years, diminishing the symptoms such as hayfever (seasonal allergic rhinitis) and other allergies (perennial rhinitis), including nasal congestion, discharge, pruritus and sneezing.[7] Mometasone can be used two to four weeks before pollen season, reducing the severity of symptoms. It is also indicated for the treatment of nasal polyps and symptoms associated with including congestion and hyposmia in adult patients over the age of 18. It can also produce nasal drip, sensation of tickling in the throat and loss of the sense of taste and smell.

Asthma

The furoate of mometasone can be employed together with formoterol for the treatment of asthma, due to its anti-inflammatory properties.[8]

Pharmacodynamics

It reduces inflammation by causing several effects:[9][10][11]

In addition to the glucocorticoid properties of mometasone furoate, it is a very potent agonist of the progesterone receptor as well as a partial agonist of the mineralocorticoid receptor.[12]

Mechanism of action

Mometasone — the metabolite of mometasone furoate

Mometasone, like other corticosteroids, possesses anti-inflammatory, antipruritic, and vasoconstrictive properties. For allergies, corticosteroids reduce the allergic reactions in various types of cells (mastocytes and eosinofiles) that are responsible for allergic reactions. Mometasone and other corticosteroids circulate in the blood easily, crossing cellular membranes and binding with cytoplasmic receptors, resulting in the transcription and synthesis of proteins. Mometasone also inhibits the actions of the enzyme cytochrome P450 2C8 which participates in the activity of monooxygenase.[13]

The inflammation is reduced in decreasing the liberation of hydrolace acids of leukocytes, the prevention of the accumulation macrophages in the sites of inflammation, the interference with adhesion of leukocytes to capillary walls, the reduction of the permeability of the capillary membranes and consequently edema, the reduction of complementary components, inhibition of histamine and kinin liberation, and interference with scar tissue formation.[14] The proliferation of fibroblasts and collagen deposits are also reduced. It is believed that the action of corticosteroid anti-inflammatory agents are bound to inhibitive proteins of phospholipase A2, collectively called lipocortins. The lipocortins, in turn, control the biosynthesis of potent mediators of inflammation as the prostaglandins and leukotrienes, inhibiting the liberation of the molecular precursors of arachidonic acid. Intranasal mometasone alleviates symptoms such as rhinorrhea aquosa, nasal congestion, nasal drip, sneezing, and pharyngeal itching. Topical administration applied to skin reduces the inflammation associated with chronic or acute dermatosis.

Metabolism

There are extensive metabolic hepatic metabolism to multiple metabolites. There do not exist principal metabolites detectable in plasma. After in vitro incubation, one of the minor metabolites formed is furoate 6β-hydroxymometasone. In human hepatic microsomes, the formation of these metabolites is regulated by cytochrome P450 3A4.

Availability

Mometasone is marketed under the brand names Elocom (and its derivatives) and Hhsone as a cream or ointment for skin conditions, Nasonex as a nasal spray for upper respiratory conditions and Asmanex Twisthaler as a dry-powder inhaler (DPI) for lower respiratory conditions.

It is also available as a veterinary drug in the form of ear drops for treatment of otitis externa under the brand name Mometamax.[15]

References

  1. ↑ Zia R. Tayab, Tom C. Fardon, Daniel K. C. Lee, Kay Haggart, Lesley C. McFarlane, Brian J. Lipworth, and Günther Hochhaus (November 2007). "Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate". Br J Clin Pharmacol 64 (5): 698–705. doi:10.1111/j.1365-2125.2007.02919.x. PMC 2203259. PMID 17509041.
  2. ↑ Tan RA, Corren J (December 2008). "Mometasone furoate in the management of asthma: a review". Ther Clin Risk Manag 4 (6): 1201–8. PMC 2643101. PMID 19337427.
  3. ↑ Bousquet J (May 2009). "Mometasone furoate: an effective anti-inflammatory with a well-defined safety and tolerability profile in the treatment of asthma". Int. J. Clin. Pract. 63 (5): 806–19. doi:10.1111/j.1742-1241.2009.02003.x. PMID 19392928.
  4. ↑ Khope S (March 2010). "Topical mometasone furoate for phimosis". Indian Pediatr 47 (3): 282. PMID 20371899.
  5. ↑ Williams D. What does potency actually mean for inhaled corticosteroids?. The Journal of Asthma. July 2005;42(6):409-417. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed October 25, 2011.
  6. ↑ Chohan, A; Lal, A; Chohan, K; Chakravarti, A; Gomber, S (13 July 2015). "Systematic review and meta-analysis of randomized controlled trials on the role of mometasone in adenoid hypertrophy in children.". International Journal of Pediatric Otorhinolaryngology 79: 1599–608. doi:10.1016/j.ijporl.2015.07.009. PMID 26235732.
  7. ↑ Stjärne, P.; Mösges R; Jorissen M; Passàli D; Bellussi L; Staudinger H; Danzig M. (Feb 2006). A randomized controlled trial of mometasone furoate nasal spray for the treatment of nasal polyposis 132. Arch Otolaryngol Head Neck Surg. pp. 179–185.
  8. ↑ Bousquet, J. (May 2009). Mometasone furoate: an effective anti-inflammatory with a well-defined safety and tolerability profile in the treatment of asthma. 63. Int J Clin Pract. pp. 806–819.
  9. ↑ Product Information: NASONEX(R) nasal spray, mometasone furoate monohydrate nasal spray. Schering Corporation, Kenilworth, NJ, 2010.
  10. ↑ Publishers, Jones and Bartlett (2009-07-15). Nurse's Drug Handbook 2010. p. 677. ISBN 978-0-7637-7900-9.
  11. ↑ Mani S. Kavuru (2007). "ch. 9 Anti-inflammatory agents". Diagnosis and Management of Asthma. ISBN 978-1-932610-38-3.
  12. ↑ Austin RJ, Maschera B, Walker A, Fairbairn L, Meldrum E, Farrow SN, et al. (2002). "Mometasone furoate is a less specific glucocorticoid than fluticasone propionate". Eur. Respir. J. 20 (6): 1386–92. doi:10.1183/09031936.02.02472001. PMID 12503693.
  13. ↑ Walsky, R. L.; Gaman EA; Obach RS. (Jan 2005). "Pharmacokientics, Pharmacodynamics, and Drug Metabolism". Examination of 209 drugs for inhibition of cytochrome P450 2C8. 45 (Pfizer Global Research and Development ed.). USA.: J Clin Pharmacol. pp. 68–78. Retrieved 2012-11-17.
  14. ↑ Blaiss, MS. (Nov 2011). Safety update regarding intranasal corticosteroids for the treatment of allergic rhinitis. 32. Allergy Asthma Proc. pp. 413–418.
  15. ↑ "Mometamax". Intervet USA. Retrieved 19 June 2010.

External links

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