Awareness of potential valvulopathy risk with pergolide and changes in clinical practice after label change: a survey among European neurologists.

In response to concern about the reported frequency of ergot-associated valvulopathy in patients with Parkinson's disease (PD), Eli Lilly and Company updated the Risk Minimization Program for pergolide, changing the Summary of Product Characteristics (SmPC) and distributing a Dear Doctor Letter (DDL) highlighting the new label changes. A survey was conducted subsequently to assess neurologists' awareness of the revised SmPC and their resulting changes in practice. A random sample of 20.3% of neurologists (n = 4056) from 12 eligible EU countries were invited to participate. Of the target population of 247 neurologists who treated patients with PD, used pergolide in 2005, and were willing to participate, 244 (99%) responded. Overall awareness of the DDL and the SmPC changes was 94.2%. Over half (58.3%) of neurologists indicated that they prescribe pergolide exclusively as second-line treatment, although some (21.9%) used pergolide exclusively as first-line treatment. In response to the DDL, most neurologists perform echocardiograms before treatment (67.5%) and during treatment (76.7%), and over half (55%) avoid prescribing doses >5 mg/day. Overall, use of a DDL to communicate an SmPC change was effective in increasing the awareness of pergolide-associated valvulopathy and in modifying neurologists' clinical practice to minimize this risk.

A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium.

OBJECTIVE: To determine the effects of a selective estrogen receptor modulator, raloxifene, on postmenopausal endometrium. METHODS: Healthy postmenopausal women (n = 415) were randomly assigned to one of the following four groups: 60 or 150 mg/day raloxifene hydrochloride, 0.625 mg/day conjugated equine estrogens, or placebo, and treated for 1 year. Endometrial biopsies were obtained in a blinded fashion at baseline and every 6 months after the ultrasound studies. Transvaginal ultrasound, with uterine size measurements, was done at baseline and at 3-month intervals. Saline-infusion sonohysterography was done at baseline and every 6 months. RESULTS: There were no statistically significant differences in baseline characteristics. Mean endometrial thickness, measured by transvaginal ultrasound, was unchanged from baseline to end point in the placebo and raloxifene groups, whereas in the estrogen group it was significantly thicker by 5.5 mm (P < .001). Mean uterine volume, calculated from transvaginal ultrasound measurements, was higher in the estrogen group only (22 cm3, P < .001). Of the 358 women with paired biopsies, endometrial hyperplasia was present in 2.1%, 0%, and 26.1% of the end-point biopsies in the placebo, raloxifene, and estrogen groups, respectively (P < .001). Proliferative endometrium was present in 2.1% of the end-point biopsies in the placebo group, 1.7% in the combined raloxifene groups, and 39.8% in the estrogen group (P < .001). CONCLUSION: Raloxifene, at 60 or 150 mg/day for 1 year, did not stimulate the postmenopausal endometrium. End-point endometrial thickness, morphology, and uterine volume in the raloxifene groups were similar to those observed at baseline and in the placebo group.