Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Orion Corporation, Orionintie 1, FI-02200 Espoo, Finland
Pharmacotherapeutic group: Sex hormones and modulators of the genital system, Natural and semisynthetic oestrogens, plain
ATC code: G03CA03
The active ingredient in Sandrena, synthetic 17β-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.
As oestrogens promote the growth of the endometrium, unopposed oestrogens increase the risk of endometrial hyperplasia and cancer. The addition of a progestagen greatly reduces the oestrogen induced risk of endometrial hyperplasia in non-hysterectomised women.
The pharmacodynamics of Sandrena are similar to those of oral oestrogens, but the major difference to oral administration lies in the pharmacokinetic profile. The clinical efficacy of Sandrena in the treatment of menopausal symptoms is comparable to that of peroral oestrogen.
Relief of menopausal symptoms was achieved during the first few weeks of treatment.
Sandrena is an alcohol-based estradiol gel. When applied to the skin the alcohol evaporates rapidly and estradiol is absorbed through the skin into the circulation. Application of Sandrena on area of 200-400 cm² (size of one to two hands) does not affect the amount of estradiol absorbed. However, if Sandrena is applied to larger area absorption decreases significantly. To some extent, however, the estradiol is stored in the subcutaneous tissue from where it is released gradually into circulation. Percutaneous administration circumvents the hepatic first-pass metabolism. For these reasons, the fluctuations in the plasma oestrogen concentrations with Sandrena are less pronounced than peroral oestrogen.
Percutaneous doses of 0.5, 1.0 and 1.5 mg of estradiol (0.5, 1.0 and 1.5 g Sandrena) result in mean Cmax concentrations in plasma of 143, 247 and 582 pmol/L, respectively. The corresponding mean Caverage concentrations over the dosing interval are 75, 124 and 210 pmol/L. The corresponding mean Cmin concentrations were 92, 101 and 152 pmol/L, respectively. During Sandrena treatment the estradiol/oestrone ratio remains between 0.4 and 0.7, while for oral oestrogen treatment it usually drops to less than 0.2.
The mean estradiol exposure at steady state of Sandrena is 82 per cent compared with an equivalent oral dose of estradiol valerate. Otherwise the metabolism and excretion of transdermal estradiol follow the fate of natural oestrogens.
Estradiol is a natural female hormone with an established clinical use, therefore no toxicological studies have been performed with Sandrena. The necessary studies on the irritant effects of the gel were studied in rabbits and skin sensitisation in guinea pig. Based on the results from these studies it can be concluded that Sandrena very infrequently could cause mild skin irritation. Skin irritation can be reduced by daily change of the application site.
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