Fluticasone propionate

Fluticasone propionate
Systematic (IUPAC) name
S-(fluoromethyl)-6α,9-difluoro-11β, 17-dihydroxy-16α-methyl-3-oxoandrosta-1, 4-diene-17β-carbothioate, 17-propanoate
Clinical data
AHFS/Drugs.com monograph
  • US: C (Risk not ruled out)
  • C for Intranasal and Inhaled
Intranasal, Inhaled, Topical Cream or Ointment
Pharmacokinetic data
Bioavailability 0.51% (Intranasal)
Protein binding 91%
Metabolism Intranasal
Hepatic (CYP3A4-mediated)
Half-life 10 hours
Excretion Renal
Identifiers
80474-14-2 Yes
D07AC17 & D07AC04 (topical)
PubChem CID 444036
DrugBank DB00588 Yes
ChemSpider 392059 Yes
UNII O2GMZ0LF5W Yes
ChEBI CHEBI:31441 Yes
ChEMBL CHEMBL1473 Yes
Chemical data
Formula C25H31F3O5S
500.57 g/mol
 Yes (what is this?)  (verify)

Fluticasone propionate belongs to a class of drugs known as corticosteroids, specifically glucocorticoids, which are hormones that predominantly affect the metabolism of carbohydrates and, to a lesser extent, fat and protein. It is used to treat asthma, allergic rhinitis, nasal polyps, various skin disorders and Crohn’s disease and ulcerative colitis. It is also used to treat eosinophilic esophagitis.

Pharmacology

Fluticasone propionate is a highly selective agonist at the glucocorticoid receptor with negligible activity at androgen, estrogen, or mineralocorticoid receptor thereby producing anti-inflammatory and vasoconstriction effects. It has been shown to have a wide range of inhibitory effects on multiple cell types (e.g. mast cell, eosinophil, neutrophil, macrophages, and lymphocytes) and mediators (e.g. histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation. Fluticasone propionate is stated to exert a topical effect on the lungs without significant systemic effects at usual doses, due to its low systemic bioavailability.

Medical uses and administration

Asthma

Fluticasone is used by powder or aerosol inhalation for the prophylaxis of asthma. Typical initial doses in the UK range from 100 to 250 micrograms twice daily in mild asthma up to 1 mg twice daily in severe asthma, adjusted according to response. Children over four years of age may be given initial doses of 50 to 100 micrograms twice daily, increased to 200 micrograms twice daily if necessary. The drug may also be given via a nebuliser in severe chronic asthma. Usual adult doses are 0.5 to 2 mg twice daily. Children aged four to sixteen years may be given 1 mg twice daily.

Allergic rhinitis

Nasal spray preparation of Fluticasone propionate is used in the prophylaxis and treatment of allergic rhinitis. The usual dose is 100 micrograms into each nostril once daily, increased if necessary to 100 micrograms into each nostril twice daily. Children over four years of age may be given half these doses.

Nasal polyps

Fluticasone propionate nasal drops are used in the treatment of nasal polyps. 200 micrograms should be instilled into each nostril once or twice daily for at least four to six weeks.

Other

Creams and ointments containing 0.05% and 0.005% Fluticasone propionate, respectively, are available and applied topically in the treatment of various skin disorders. It can be given orally in the treatment of Crohn’s disease and ulcerative colitis. Some benefit was also reported in coeliac disease. The dose is 5 mg four times daily but some consider higher doses necessary.

Adverse effects

If taken correctly, the nasal spray and oral inhaler formulation have less corticosteroid side effects than the tablet formulation because they limit systemic (blood) absorption.[1] However, if the spray or inhaler is used at higher than recommended doses or with other corticosteroids, serious side effects can occur.[1][2] These systemic corticosteroid side effects include weakened immune system, increased risk of systemic infections, osteoporosis, and elevated pressure in the eyes.[3]

Nasal spray

Common side effects may include nasal irritation, headache, nausea, vomiting, diarrhea, nosebleed, and cough. Rare side effects include painful white patches in nose or throat, sore throat, bruising, vision problems, swelling of face or neck, and difficulty breathing or swallowing.[4]

Oral inhaler

Common side effects may include upper respiratory tract infection, throat irritation, thrush, cough, and headache. Rare side effects include bruising, swelling of the face/neck, depression, tiredness, and shortness of breath.[5]

Interactions

Fluticasone propionate is broken down by cytochrome P450 3A4, CYP3A4, and has been shown to interact with strong CYP3A4 inhibitors such as ritonavir and ketoconazole.[1][2]

Ritonavir is a common drug used in the treatment of HIV. Coadministration of ritonavir and fluticasone may lead to increased levels of fluticasone in the body, which may lead to Cushing’s Syndrome and adrenal suppression.[6]

Ketoconazole, an antifungal drug, has also been shown to increase fluticasone concentration leading to systemic corticosteroid side effects.[1][2]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 Flonase[package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2003.
  2. ↑ 2.0 2.1 2.2 Flovent[package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2014
  3. ↑ http://www.mayoclinic.org/steroids/art-20045692?pg=2
  4. ↑ AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; ©2008. Fluticasone Nasal Spray; [revised 2010 Sept 1; reviewed 2010 Sept 1; cited 2014 Nov 2]; [about 1 p.]. Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a695002.html
  5. ↑ AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; ©2008. Fluticasone Oral Inhalation; [revised 2010 Sept 1; reviewed 2010 Sept 1; cited 2014 Nov 2]; [about 1 p.]. Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601056.html
  6. ↑ Foisy, M., Yakiwchuk, E., Chiu, I. and Singh, A. (2008), Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Medicine, 9: 389–396. doi: 10.1111/j.1468-1293.2008.00579.x