Momeclir Mechanism of Action

Pharmacotherapeutic group: Decongestants and other nasal preparations for topical use-corticosteroids.
Pharmacology: Pharmacodynamics: Mechanism of Action: Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties at doses that are not systemically active.
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. Mometasone furoate significantly inhibits the release of leukotrienes from leukocytes of allergic patients. In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNFα; it is also a potent inhibitor of leukotriene production. In addition, it is an extremely potent inhibitor of the production of the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.
Pharmacodynamic effects: In studies utilizing nasal antigen challenge, Mometasone furoate nasal spray suspension 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 suspension 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.
Pediatric population: In a placebo-controlled clinical trial in which pediatric patients (n=49/group) were administered Mometasone furoate nasal spray 100 micrograms daily for one year, no reduction in growth velocity was observed.
There are limited data available on the safety and efficacy of Mometasone furoate nasal spray in the pediatric population aged 3 to 5 years, and an appropriate dosage range cannot be established. In a study involving 48 children aged 3 to 5 years treated with intranasal Mometasone furoate 50, 100 or 200 μg/day for 14 days, there was no significant differences from placebo in the mean change in plasma cortisol level in response to the tetracosactrin stimulation test.
The European Medicines Agency has waived the obligation to submit the results of studies with Mometasone furoate Nasal spray suspension in all subsets of the pediatric population in seasonal and perennial allergic rhinitis.
Pharmacokinetics: Absorption: Mometasone furoate, administered as an aqueous nasal spray suspension, has a systemic bioavailability of <1% in plasma, using a sensitive assay with a lower quantitation limit of 0.25 pg/mL.
Distribution: Not applicable as Mometasone is poorly absorbed via the nasal route.
Biotransformation: The small amount that may be swallowed and absorbed undergoes extensive first-pass hepatic metabolism.
Elimination: Absorbed Mometasone furoate is extensively metabolized and the metabolites are excreted 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 fetal growth (lower fetal 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 concentration 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 tumor types.