Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: Besins Healthcare (UK) Ltd, Lion Court, 25 Procter Street, Holborn, London, WC1V 6NY, United Kingdom
Pharmacotherapeutic group: natural and semisynthetic estrogens, plain,
ATC code: G03CA04
The active ingredient, semisynthetic estriol, is chemically identical to human estriol which is produced naturally in the body. Vaginally applied estriol alleviates the symptoms of vaginal atrophy due to estrogen deficiency in postmenopausal women. Instead of an atrophic cell profile mainly intermediate cells and an increasing number of superficial cells are found in the vagina; inflammatory disorders disappear and restoration of the vaginal Lactobacillus flora (Doederlein’s flora) is supported.
Superiority of IMVAGGIS 0.03 mg pessary over placebo in the local treatment of vaginal atrophy was shown in a randomized double-blind clinical trial involving 438 postmenopausal women. Intravaginal administration of low-dose IMVAGGIS 0.03 mg pessary resulted in a significant improvement of objective efficacy variables (vaginal maturation index, vaginal pH) as well as in a considerable alleviation of subjective symptoms (Most Bothersome Symptoms/MBS) after 12 weeks of treatment (p-value <0.001 for all 3 parameters).
A pharmacokinetic study was performed in postmenopausal women with diagnosed vaginal atrophy in order to investigate the extent of systemic exposure to estriol from IMVAGGIS 0.03 mg pessary. Treatment was by the vaginal route once daily for 21 days. A single dose of 0.03 mg estriol increased mean estriol peak plasma concentration (Cmax) to 42.11 pg/ml one hour after dosing. Twelve hours after administration the estriol concentration had decreased to below 5 pg/ml (LLoQ) in all patients. After daily treatment for 21 days the peak concentration was 11.9 pg/ml two hours after dosing. This value remains in the range of postmenopausal estriol plasma concentrations. The average concentration (Cav) after multiple dosing was 2.2 pg/ml. In plasma about 8% of estriol is available in its free form, 91% is bound to albumin and 1% to SHBG.
Metabolism in the liver mainly leads to glucuronides and sulfates.
Estriol is mainly excreted in its conjugated form via the kidneys and in a small fraction via the bile.
The toxicological properties with estrogens are well known. Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenic potential, beyond that which has already been considered in other sections of this summary of product characteristics.
Preclinical data are not available for vaginal administration.
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