Source: Health Products Regulatory Authority (IE) Revision Year: 2017 Publisher: Almirall Hermal GmbH, Scholtzstraße 3, D-21465 Reinbek, Germany Phone: +49 40 727 04 0 Fax: +49 40 72 704 329 E-mail: info@almirall.de
Pharmacotherapeutic group: Corticosteroids, Dermatological preparations; Corticosteriods, potent (Group III)
ATC Code: D07AC13
Monovo is a potent glucocorticoid, group III.
The active substance, mometasone furoate, is a synthetic, non-fluorinated glucocorticoid with a furoate ester in position 17.
Like other corticosteroids for external use, mometasone furoate exhibits marked anti-inflammatory activity and marked anti-psoriatic activity in standard animal predictive models.
Monovo was shown to have an equivalent pharmacodynamic (vasoconstriction) response profile to the reference product containing 1mg/g mometasone furoate when applied to normal skin. The calculated AUC ratio of Monovo to the reference product in the vasoconstrictor assay was 97.06%.
The therapeutic index of mometasone furoate (a ratio of desired to unwanted effects) determined from relevant literature data suggests that mometasone belongs to a category of topical glucocorticoids, in which desired effects clearly outweigh unwanted effects.
In the croton oil assay in mice, mometasone (ED50 = 0.2 µg/ear) was equipotent to betamethasone valerate after single application and about 8 times as potent after five applications (ED50 = 0.002 µg/ear /day versus 0.014 µg/ear/day).
In guinea pigs, mometasone was approximately twice as potent as betamethasone valerate in reducing m.ovalis-induced epidermal acanthosis (i.e. anti-psoriatic activity) after 14 applications.
Results from percutaneous absorption studies have indicated that systemic absorption following topical application of mometasone furoate cream 0.1% is minimal. The results show that about 0.4% of the active ingredient is absorbed by the intact skin in 8 hours (without using an occlusive dressing).
Characterization of metabolites was not feasible owing to the small amounts present in plasma and excreta.
| Type of Animal | Type of Application | LD50 (mg/kg) |
|---|---|---|
| Mouse | subcutaneous | 200–2000 |
| Rat s | ubcutaneous | 200 |
| Dog | subcutaneous | >200 |
| Mouse | oral | >2000 |
| Rat | oral | >2000 |
In various toxicity studies with chronic use in which excessive quantities of the active ingredient (670 times the therapeutic dose) were applied over 6 months, only symptoms typical of corticoid overdose were found: reduced weight gain; muscular atrophy; distended abdomen; decrease in lymphocytes and eosinophilic granulocytes and increase in neutrophilic leucocytes; increase in serum transaminases (SGPT and SGOT), cholesterol and triglycerides; lipidaemia; organ changes (atrophy of the spleen and thymus, local skin atrophy, increases in liver and kidney weight and reduced osteogenesis).
These changes were generally more pronounced and more frequent in animals which were given the comparison substance, betamethasone valerate. Neither of the two substances exhibited unusual systemic effects.
Tests on gene mutations were negative. However, mometasone induced chromosome mutations in-vitro but only at cell-toxic concentrations. Similar effects were not observed in thorough in-vivo tests, so a mutagenic risk can be ruled out with sufficient certainty.
Long-term carcinogenicity studies of mometasone furoate have been conducted by the inhalation route in rats (2 years) and mice (19 months). No statistically significant increase in the incident of tumours was observed at doses up to 67 mcg/kg in rats or 160 mcg/kg in mice.
Animal tests on the effect of mometasone furoate on embryonic development in rabbits revealed depressed body weight from 0.15 mg/kg/BWT upwards.
After topical treatment of rabbits, the progeny suffered various types of malformation, such as crooked front paws, cleft palate, gallbladder agenesis and umbilical hernia. In the rat, embryo-lethal effects from 7.5 µg//kg/BWT (subcutaneous) and poor development from 0.3 mg/kg/BWT (topical) (depressed body weight, delayed ossification) and substancerelated increase in umbilical hernia were observed. When the drug was administered to mothers close to the birth date, protracted labour and difficult births were observed.
Mometasone furoate had no effects on the fertility of rats.
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