Lafamme (R): A new oral preparation for continuous combined hormone replacement therapy in postmenopausal women

The fixed formulation containing 2 mg estradiol valerate and 2 mg dienogest (Lafamme(R)) has been developed for continuous hormone replacement therapy (HRT) in postmenopausal women. In this review, the clinical data on pharma cokinetics, efficacy, tolerability and safety of this combination are summa rized. After multiple-dose administration to postmenopausal women, estradio l and free estrone accumulated to a significantly greater extent than that predicted from single-dose data. However, total estrone accumulation was wi thin the predicted range. The dienogest kinetics was linear and not time de pendent. During the treatment of 1,500 postmenopausal patients with this fo rmulation, the Kuppermann index as the primary target parameter of climacte ric complaints, was significantly improved. The changes were independent of whether a patient had received HRT prior to joining the study and the type of HRT. In a double-blind randomized phase III study over 1 year, Lafamme( R) was found to be therapeutically equivalent to Kliogest(R) [containing 2 mg estradiol, 1 mg estriol, 1 mg norethisterone acetate (NETA)]. With regar d to endometrial safety, the histological findings showed an atrophic endom etrium in nearly 90% of the women. No hyperplastic endometrium was found in any of them. Adverse drug reactions (ADRs) assessed as related to therapy were reported by 1,834 women treated with this combination. Predominant wer e ADRs regarding the reproductive system (40.7% of the women), the central and peripheral nervous systems (10.0%), and the digestive system (6.7%). Th ere were 116 serious adverse events, of which 29 were suggested to be drug related. The influence of Lafamme(R) on lipid parameters, surrogate paramet ers of vascular function, and bone-specific markers indicates favorable eff ects with regard to the risk of atherosclerosis and osteoporosis. (C) 2001 Prous Science. All rights reserved.