CIBA-GEIGY's ESTRADERM (ESTRADIOL) TRANSDERMAL PATCH EFFECTIVENESS

CIBA-GEIGY's ESTRADERM (ESTRADIOL) TRANSDERMAL PATCH EFFECTIVENESS in the treatment of post-menopausal symptoms has been "adequately demonstrated," FDA's Fertility and Maternal Health Drugs Advisory Cmte. unanimously agreed at its Dec. 19 meeting. Asked by FDA if "the efficacy of Estraderm ]has[ been adequately demonstrated despite its inability in one study not to decrease gonadotrophic secretion below 50 mIU," the cmte. voted yes. Cmte. consultant David Archer, MD, University of Pittsburgh School of Medicine, commented: "I think Estraderm is definitely efficacious" and the gonadotropic level obtained with the drug appears to be the same as that obtained with conjugated equine estrogen. Ciba-Geigy's largest study was a 10-week placebo controlled comparison of Estraderm .1 mg to Ayerst's Premarin conjugated equine estrogen .625 mg and 1.25 mg tabs in 112 postmenopausal women who had been stabilized on Premarin. The firm reported that Estraderm provided "essentially equivalent control" of postmenopausal symptoms such as hot flashes. FDA's questions to the cmte. centered on the efficacy of Estraderm. For example, FDA asked if the "presence of equilin due to an inadequate washout period ]in one particular study[ biased the evidence for the efficacy of Estraderm TTS?" Noting that the "issues of safety" had already been resolved, Ad Hoc Cmte. Chairman George Tagatz, MD, University of Minnesota, said that because subjects as they "came off Premarin went into the treated group ]while[ others went into the placebo group . . . the study would have biased the results toward no effect" instead of toward a positive effect. FDA also asked if "the proposed labeling ]should[ indicate potentially serious skin reactions." Based on Ciba-Geigy's studies, in which patients using Estraderm had skin reactions ranging from no reaction to transitory partial erethema at the site of occlusion, the cmte. agreed that a warning against "serious" skin reactions was unnecessary. Reflecting cmte. consensus, cmte. member Martin Pernoll, MD, Tulane University School of Medicine, said: "I think that the information we were provided about their potential labeling is quite clear; they indicate that only localized irritation has been observed at the site and I don't think that needs further clarification." Several cmte. members noted that patient compliance with the bi-weekly application of Ciba-Geigy's patch might be improve if the company used a calendar or colored patch wrappers in the packaging of the product so that patients would be reminded of when to put on a new patch and when to take progesterone. Tagatz commented, "I like the calendar; then they always know what day of the month they're always supposed to be on Provera ]upjohn's medroxyprogesterone[ and they know what day of the month they're supposed to take estrogen." Ciba-Geigy said it would consider the cmte.'s suggestions for packaging of the product. Estraderm, which utilizes Alza's transdermal patch delivery system, has been studied using the hip or abdomen as the area of application. National Institutes of Health cmte. consultant Florence Haseltine, MD, commented that the location of the patch might also cause compliance problems. She said: "There is a real question about location of the patch because of compliance. I think a woman's choice of where those things are placed makes a considerable amount of difference" in compliance. Ciba-Geigy noted that it would have to do additional studies in patch application on other parts of the body for the labeling to give patients a choice of application location.