CLINICAL-EXPERIENCE WITH A 7-DAY ESTRADIOL TRANSDERMAL SYSTEM FOR ESTROGEN REPLACEMENT THERAPY

OBJECTIVE: To describe the efficacy, safety, and wearability of estrog en replacement therapy of a 7-day estradiol transdermal system (Climar a), developed using new drug-in-adhesive technology. STUDY DESIGN: The pharmacokinetics of the 7-day system were investigated in single- and multiple-dose studies, a relative bioavailability study or the two pa tch sizes, and comparative studies with the twice-weekly transdermal s ystem (Estraderm). Safety and efficacy in the treatment of vasomotor s ymptoms compared with conjugated equine estrogens (Premarin) and place bo were evaluated in two 11-week, randomized, double-blind, multicente r trials in 603 women; the data are combined in this report. Irritatio n and adhesion were also evaluated in comparative studies with Estrade rm, Micropore (an inert once-weekly tape), and placebo controls. RESUL TS: Blood levels were sustained for the full 7 days of patch wear, the re was no drug accumulation, and a physiologic estrone to estradiol ra tio was maintained. Pharmacokinetics studies showed dose proportionali ty of the 0.05 and 0.1 mg/day patches. Both patch sizes significantly decreased the frequency of hot flushes compared with placebo and were comparable with conjugated equine estrogens. There was a statistically significant difference between the two patch sizes. The mean overall decline in the hot flush rate was 74.6% for the 0.1 mg patch versus 64 .5% for the 0.05 mg patch (p less than or equal to 0.05). The combined data also showed that the onset of efficacy is within 1 to 2 weeks af ter the start of therapy and that efficacy is fully sustained during t he 7-day patch wear period with some diminution of effect during the t reatment-free week of each cycle. Treatment was well tolerated. Advers e events led to withdrawal from the studies in 8.9% of subjects. In mo st of these (6.8% of subjects), the cause was adverse skin reactions. Skin irritation was similar to Estraderm in comparative studies, where as adhesion was significantly better with Climara. CONCLUSION: The Cli mara patch delivers estradiol for a full 7 days. Clinical efficacy of both patch sizes is comparable with currently accepted therapy and is sustained for the entire week of patch wear. A significant difference in response between the two doses supports dose titration. The patch i s well tolerated and has excellent adhesion.