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Fluticasone propionate is a synthetic trifluorinated glucocorticoid which exhibits antiallergic, anti-inflammatory, and antipruritic effects.
Fluticasone propionate is a synthetic trifluorinated glucocorticoid which exhibits antiallergic, anti-inflammatory, and antipruritic effects. [1,2] It is available as sprays, inhalers, nasal, and topical therapies for various inflammatory indications. [1]
Pharmacological Class: Corticosteroids
It shows a direct local effect of vasoconstriction and anti-inflammatory activity. It suppresses the initial inflammatory events such as vascular permeability, vasodilation, and leukocyte emigration. It also reduces inflammatory cells such as monocytes, macrophages, mast cells, eosinophils, and dendritic cells and the number of cytokines.
It also stimulates beta-2 receptors
on airway smooth muscle and minimizes mucus gland secretions. It also increases
the anti-inflammatory effects of annexin-1, secretory leukoprotease inhibitor
(SLPI), mitogen-activated kinase phosphatase-1 (MKP-1), glucocorticoid-induced
leucine zipper protein (GILZ), and I-kappa B-alpha and inhibitor of nuclear
factor (NF)-kappa B.
Recommended starting dosages for allergic and non-allergic
rhinitis, nasal polyps, and allergies:
Recommended starting dosages for asthma:
Absorption
The oral bio-availability is <1% while the intranasal bio-availability is <2%. The intranasal exposure leads to the majority of the dosage being swallowed. Topical absorption is very low but can alter depending on various factors including skin integrity and the presence of disease or inflammation.
Volume
of distribution
The volume of distribution of intravenous fluticasone propionate is about 4.2 l/kg.
Protein binding
It is 99% protein-bound in serum while the topical fluticasone propionate is only 91% protein-bound in serum.
Metabolism
It is cleared by cytochrome P450 3A4 via hepatic metabolism. It is hydrolyzed
at the FIVE-S-fluoromethyl carbothioate group, leading to the formation of an
inactive metabolite.
Route
of elimination
It is predominantly eliminated in the feces with <5% excreted in the urine.
Half-life
The half-life for intravenous fluticasone propionate is 7.8 hours.
Clearance
The clearance of fluticasone propionate is 1093mL/min. The total blood clearance is quite elevated (average: 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total.[1,3]
Concomitant use of strong CYP3A4
inhibitors (such as voriconazole, ritonavir,
itraconazole, atazanavir, clarithromycin, indinavir, ketoconazole,
telithromycin, lopinavir) with fluticasone propionate is not recommended, as its
coadministration can raise the risk of systemic
corticosteroid noxious effects.
Most common adverse reactions (>3%) observed in clinical
trials are:
Adverse events reported during post-approval usage of
intranasal fluticasone propionate:
Adverse events observed with systemic and local use:
Study compares tolerability and safety of fluticasone propionate tablet to treat eosinophilic oesophagitis
A study demonstrated efficacy and safety of APT-1011, a new oral disintegrating tablet formulation of fluticasone, in adolescents and adults with eosinophilic oesophagitis. Two dosing regimens of APT-1011 were given orally to patients for over eight weeks.
The effect of APT-1011 on clinical symptoms of eosinophilic oesophagitis, endoscopic appearance, and oesophageal mucosal eosinophil count/eosinophilia was determined. The major outcomes was determination of safety and tolerability. The exploratory outcomes were assessment of histologic and endoscopic measures.
APT-1011 therapy led to an elevated decrease in oesophageal eosinophil counts, eosinophilic oesophagitis Endoscopic Reference Score, patient global assessment, and symptom-based eosinophilic oesophagitis activity index from baseline to end of therapy (Week 8) in comparison with placebo. No mortality, serious or severe treatment-emergent adverse events (TEAEs), and discontinuations from the trial associated with TEAE were witnessed.
In one individual allocated to 1.5 mg APT-1011, a decline in cortisol was noted, but without any proof of adrenal insufficiency. Exploratory efficacy outcomes illustrated improvement in symptoms, endoscopic and histologic findings. Thus, APT-1011, a new orally disintegrating tablet formulation of fluticasone is safe and well-tolerated and thus offers an effective therapeutic strategy to manage patients suffering from eosinophilic oesophagitis.[5]
Fluticasone propionate found to improve nasal symptoms of seasonal allergic rhinitis
In a randomized trial, fluticasone propionate aqueous nasal spray 200 mcg used as needed (FP200PRN) was found to effectively treat nasal symptoms (nasal congestion, rhinorrhea, nasal itching, and sneezing) linked with seasonal allergic rhinitis in patients 12 years and older.
This study was carried out to explore the efficacy and
safety of four weeks treatment with FP200PRN in 241 patients suffering from
seasonal allergic rhinitis. Fluticasone propionate was also found to have a
minimized occurrence of side effects in comparison with regular once-daily
usage.
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