Mometasone Sandoz Mechanism of Action

Pharmacotherapeutic group: Decongestants and other nasal preparations for topical use-corticosteroids. ATC Code: R01A D09.
Pharmacology: Pharmacodynamics: Mechanism of action: Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties.
It is likely that much of the mechanism for the anti-allergic and anti-inflammatory effects of mometasone furoate lies in its ability to inhibit the release of mediators of allergic reactions.
Clinical efficacy and safety: In studies utilising nasal antigen challenge, mometasone furoate nasal spray has shown anti-inflammatory activity in both the early- and late- phase allergic responses. This has been demonstrated by decreases (vs placebo) in histamine and eosinophil activity and reductions (vs baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins.
In 28% of the patients with seasonal allergic rhinitis, mometasone furoate nasal spray demonstrated a clinically significant onset of action within 12 hours after the first dose. The median (50%) onset time of relief was 35.9 hours.
Paediatric population: In a placebo-controlled clinical trial in which paediatric patients (n=49/group) were administered mometasone furoate nasal spray 100 micrograms daily for one year, no reduction in growth velocity was observed.
Pharmacokinetics: Mometasone furoate, administered as an aqueous nasal spray, has a negligible (<1%) systemic bioavailability and is generally undetectable in plasma, despite the use of a sensitive assay with a lower quantitation limit of 50 pg/ml; thus, there are no relevant pharmacokinetic data for this dosage form. Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract, and the small amount that may be swallowed and absorbed undergoes extensive first-pass hepatic metabolism prior to excretion in urine and bile.
Toxicology: Preclinical safety data: No toxicological effects unique to mometasone furoate exposure were demonstrated. All observed effects are typical of this class of compounds and are related to exaggerated pharmacologic effects of glucocorticoids.
Preclinical studies demonstrate that mometasone furoate is devoid of androgenic, antiandrogenic, estrogenic or antiestrogenic activity but, like other glucocorticoids, it exhibits some antiuterotrophic activity and delays vaginal opening in animal models at high oral doses of 56 mg/kg/day and 280 mg/kg/day.
Like other glucocorticoids, mometasone furoate showed a clastogenic potential in-vitro at high concentrations. However, no mutagenic effects can be expected at therapeutically relevant doses.
In studies of reproductive function, subcutaneous mometasone furoate, at 15 micrograms/kg prolonged gestation and prolonged and difficult labour occurred with a reduction in offspring survival and body weight or body weight gain. There was no effect on fertility.
Like other glucocorticoids, mometasone furoate is a teratogen in rodents and rabbits. Effects noted were umbilical hernia in rats, cleft palate in mice and gallbladder agenesis, umbilical hernia, and flexed front paws in rabbits. There were also reductions in maternal body weight gains, effects on foetal growth (lower foetal body weight and/or delayed ossification) in rats, rabbits and mice, and reduced offspring survival in mice.
The carcinogenicity potential of inhaled mometasone furoate (aerosol with CFC propellant and surfactant) at concentrations of 0.25 to 2.0 micrograms/l was investigated in 24-month studies in mice and rats. Typical glucocorticoid-related effects, including several non-neoplastic lesions, were observed. No statistically significant dose-response relationship was detected for any of the tumour types.
The preclinical data show that benzalkonium chloride could have inhibitory effects on the cilia including irreversible standstill, dependent on the concentration and duration of treatment with this excipient. Also, histopathological changes of the nasal mucosa were induced.