Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Novartis Pharmaceuticals UK Limited, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR
Pharmacotherapeutic group: Oestrogens
ATC code: G03CA03
The active substance in Estradot, synthetic 17ฮฒ-estradiol, is chemically and biologically identical to endogenous human estradiol. It substitutes for the loss of oestrogen production in menopausal women and alleviates menopausal symptoms.
Relief of menopausal symptoms was achieved during the first few weeks of treatment.
Transdermal administration of estradiol achieves therapeutic plasma concentrations using a lower total dose of estradiol than required with oral administration, whereas plasma levels of estrone and estrone conjugates are lower with the transdermal route.
In studies in postmenopausal women with application of Estradot 25, 37.5, 50, and 100 ยตg/24 hours patches, average peak estradiol serum levels (Cmax) were approximately 25 pg/ml, 35 pg/ml, 50-55 pg/ml and 95-105 pg/ml, respectively. Linear pharmacokinetics have been demonstrated for estradiol following transdermal administration.
At steady state, after repeated applications of Estradot 50 ยตg/24 hours patches, Cmax and Cmin values were 57 and 28 pg/ml for estradiol and 42 and 31 pg/ml for estrone, respectively.
Estradiol is more than 50% bound to plasma proteins such as sex hormone binding globulin and albumin. Only 2% is free and biologically active.
Transdermally applied estradiol is metabolised in the same way as the endogenous hormone. Estradiol is metabolised primarily in the liver to estrone, then later to estriol, epioestriol and catechol estrogens, which are then conjugated to sulphates and glucuronides. Cytochrome 450 isoforms CYP1A2 and CYP3A4 catalyze the hydroxylation of estradiol forming estriol. Estriol is glucuronidated by UGT1A1 and UGT2B7 in humans. Estradiol metabolites are subject to enterohepatic circulation.
The sulphate and glucuronide esters along with a small proportion of estradiol and several other metabolites are excreted in the urine. Only a small amount is excreted in faeces. Since estradiol has a short half-life (approximately one hour), serum concentrations of estradiol and estrone returned to baseline values within 24 hours following removal of the patch.
The toxicity profile of estradiol has been well established. Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver as well as the frequency of lymphoid and pituitary tumours.
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