Background: The estimated estradiol (E2) dose required for pubertal induction in hypogonadal girls is about 1/10 of the adult dose. Previous studies have shown that it is possible to provide an individualized and physiological dose for pubertal induction by cutting the patch into smaller pieces. However, the manufacturers do not guarantee stability or utility of cut E2 patches, primarily designed for postmenopausal women, and have no interest in that evaluation.
Objective: To assess the distribution of E2 drug over the surface area on different brands of patches and test sustainability of cut pieces.
Methods: Four different E2 matrix patches available in Europe were tested; all guaranteed by the manufacturer to sustain until expire date by storage in its sachet <+25C or <+30C. 1. Oesclim® 25 μg (Mylan Technologies). Rectangular (11 cm2), containing 5 mg E2. 2. Estraderm MX® 50 μg (Merus Labs). Square-shaped (22 cm2), containing 1.5mg E2. 3. Estradot® 50 μg (Novartis). Rectangular (5 cm2), containing 0.78mg E2. 4. Systen® (=Evorel®); 50 μg (Janssen-Cilag International). Square-shaped (16 cm2), containing 3.2 mg E2. Oesclim, Estraderm and Systen patches were cut into eight parts while Estradot (small patch) was cut into two parts. Patch pieces were put back into respective sachet and sealed by hand. Half of the sachets were put in plastic bags and sealed. The patches were stored at room temperature (+2022C) or at +35C in heating cabinet for up to 1 month. The E2 drug was extracted from the patch in a solution of ethyl acetate n-hexane, serially diluted and determined by RIA. A CV below 20% was considered as an acceptable variance in E2 concentrations between cut pieces.
Results: E2 drug concentrations were evenly distributed on Oesclim, Estraderm and Systen surface area. Storage in +2022C or +35C up to 1 month did not affect the E2 drug amount. E2 in Estradot patch however, was not affected by storage in +2022C, but in +35C E2 decreased with 33% (±15%) in sealed patches and 60% (±13%) in cut patches, during 1 month storage. Storage in plastic bags gave the same results as storage without.
Conclusion: Sustainability of cut Oesclim®, Estraderm® and Systen® patches was achieved for at least 1 month in room temperature or +35C. The Estradot patch was too small to properly cut into small pieces and not sustainable in warm climate.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology