FEMSEVEN Transdermal patch Ref.[28030] Active ingredients: Estradiol

Source: Medicines & Healthcare Products Regulatory Agency (GB)  Revision Year: 2020  Publisher: Theramex Ireland Limited, 3rd Floor, Kilmore House, Park Lane, Spencer Dock, Dublin 1, D01 YE64, Ireland

5.1. Pharmacodynamic properties

ATC code: G03A03

Oestrogens

The active ingredient, 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. Oestrogens prevent bone loss menopause or ovariectomy.

Clinical Trial Information

Relief of oestrogen-deficiency symptoms and bleeding patterns:

  • Relief of menopausal symptoms was achieved during the first few weeks of the treatment. In non-hysterectomised women, the bleeding profile depends on the type and dose of the progestagen and duration used in combination with FemSeven.
  • Prevention of osteoporosis
    • Oestrogen deficiency at menopause is associated with an increasing bone turnover and decline in bone mass.
    • The effect of oestrogens on the bone mineral density is dose-dependent. Protection appears to be effective for as long as treatment is continued. After discontinuation of HRT, bone mass is lost at a rate similar to that in untreated women.
    • Evidence from the WHI trial and meta-analysed trials shows that current use of HRT, alone or in combination with a progestagen – given to predominantly healthy women – reduces the risk of hip, vertebral, and other osteoporotic fractures. HRT may also prevent fractures in women with low bone density and/or established osteoporosis, but the evidence for that is limited.

5.2. Pharmacokinetic properties

After application of the transdermal system containing estradiol, therapeutic concentrations of estradiol are achieved within 3 hours and maintained throughout the entire application period of the transdermal patch (7 days). Estradiol peak plasma concentrations (Cmax) range from 59 to 155 pg/ml (baseline corrected geometric mean 92 pg/ml) and AUC0-168h values were between 2478 and 10694 h*pg/ml (baseline corrected geometric mean 5188 h*pg/ml). The mean average plasma concentration (Cav) is 42 pg/ml (range: 20 to 145 pg/ml) and mean Cpre (trough concentration before next patch application) is 29 pg/ml. After removal of the transdermal patch, estradiol concentrations return to pre-treatment values (below 10 pg/ml) within 12 hours.

By transdermal administration of FemSeven, there is no hepatic first-pass effect and the estradiol reaches the bloodstream directly in unchanged form and in physiological amounts. With the use of FemSeven, the estradiol concentrations are raised to values similar to those of the early to middle follicular phase.

The liver is the major site for estradiol metabolism. The primary metabolites are estrone, estriol and their conjugates (glucuronide and sulfate). Estradiol is excreted into the urine mostly as glucuronide and sulfate. The urinary excretion approaches pre-treatment levels within 24 hours after patch removal.

5.3. Preclinical safety data

Animal studies with estradiol have shown expected estrogenic effects.

There are no preclinical data of relevance to the prescriber that are additional to those already included in other sections of the SPC (see notably section 4.6).

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