Estradiol Gel 0.06% (Elestrin™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
The FDA has approved an estradiol gel for the management of hot flashes associated with menopause. The formulation provides the lowest dose of estradiol approved to date. It will be marketed by Kenwood Pharmaceuticals as Elestrin.
Estradiol gel is approved for the treatment of moderate to severe vasomotor symptoms associated with menopause.1
The recommended dose is 0.87 g (one pump actuation) applied once daily to the upper arm to the shoulder (320 cm2). One actuation delivers 12.5 mcg/day and two (1.7 g), 37.5 mcg/day. A progestin should be coadministered in patients with a uterus to reduce the risk of endometrial cancer.
Elestrin will be available as a 144 g metered-dose pump delivering 100 doses of 0.87 g per actuation.
Estradiol gel provides a transdermal delivery of estradiol with the lowest dose of estradiol. A 0.87 g delivers 12.5 mcg of estradiol and provides a means plasma level of 15.4 pg/ml.1
Elestrin is not approved for treating vaginal symptoms or osteoporosis. The gel is less elegant than the transdermal patch as it needs to be applied to the upper arm and 5 minutes must be allowed for the gel to dry before dressing. The gel contains alcohol and is flammable. Direct skin contacts with others should be avoided for 2 hours. Concomitant application of a sunscreen at the same site as Elestrin increases exposure to estradiol.1 A sunscreen can be applied 25 minutes after application of the gel. CYP3A4 inducers and inhibitors can reduce and increase plasma levels of estradiol respectively.1
Estradiol gel delivers 12.5 mcg/day and provides a mean plasma concentration of estradiol of 15.4 pg/ml after 14 days of administration. The lowest patch deliver 25 mcg/day and provides 24.5 pg/ml (eg, Alora).2 In a placebo controlled trial (n = 415) estradiol gel significantly reduced the number of hot-flushes per day as well as severity score/day. The numbers of hot flushes were reduced, at week 12, by 76%, 64%, and 40% for estradiol gel 1.7 g/day, 0.87 g/day, and placebo respectively from a baseline frequency of about 13 per day by week 12. Severity was reduced by 50%, 33%, and 12.5% from a baseline value of 2.4 (1 = mild, 2 = moderate, 3 = severe). Statistical difference was observed at week 5 for the lower strength and week 4 for the higher strength. The product is expected to be available in the summer of 2007.
Findings from the Women's Health Study suggest that estrogens may increase the risk of stroke and DVT and estrogen/progestin may increase the risks of breast cancer, cardiovascular events, DVT, and dementia. Therefore these should be used at the lowest effective dose and for the shortest period of time. Patients should be reevaluated every 3 to 6 months. The gel is not approved for the treatment of vulvar or vaginal atrophy associated with menopause. These are best treated with topical vaginal products rather than topical estrogen. The cream and vaginal ring appears to be equally effective.3 Elestrin provides a low dose of estradiol for vasomotor symptoms associated with menopause.
1. Elestrin Product Information. Kenwood Therapeutics. December 2006.
2. Alora Product Information. May 2005. Watson Pharma, Inc.
3. Suckling J et al. Cochrane Database Syst Rev. 2006;Oct18;(4):CD001500.