[Prescription of ergot derivatives for lactation inhibition in France: Current practices]. / Pratiques de prescription des dérivés de l'ergot de seigle dans l'inhibition de la lactation en France.

OBJECTIVES: To provide an overview of ergot derivatives prescription for lactation inhibition in France, either label (bromocriptine 2.5mg and lisuride 0.2mg) or off-label prescription (dihydroergocryptine and cabergoline). PATIENTS AND METHODS: Analysis based on a questionnaire sent to all 618 French maternity wards in 2009, and prescription modalities from social security reimbursement data in the Rhône-Alpes region. RESULTS: The mean response rate to the questionnaire was 43% and main characteristics of respondents in this sample were very close to those found at the national level. The use of bromocriptine (89%) was the most frequently proposed. Dihydroergocryptine and cabergoline were mentioned as first or second alternatives in 39 and 24% of cases, respectively. Lisuride, homeopathy and phytotherapy were very rarely mentioned. The analysis of social security reimbursement data in the Rhône-Alpes region between 2008 and 2009 evidenced an increase in the rate of dihydroergocryptine prescriptions (from 37 to 46%), which were more frequent in women also treated with cardiovascular or psychotropic drugs, while that of bromocriptine decreased. CONCLUSION: This study shows that, in France, the main alternative to bromocriptine for lactation inhibition is the off-label use of dihydroergocryptine followed by cabergoline, which seems to be safer.

Bioequivalence of a novel high-dose oral formulation of alpha-dihydroergocryptine.

The plasma pharmacokinetics of alpha-dihydroergocryptine (DHEC, CAS 14271-05-7) were investigated in 24 patients with Parkinson disease after the administration of repeated oral doses of 40 mg DHEC twice daily by means of a novel 40 mg DHEC tablet (Almirid 40 mg test T) and an established 20 mg DHEC tablet (Almirid 20 mg - reference R). The trial was conducted according to a randomised, controlled, open, within-subject cross-over design; steady-state was established by means of a stepwise up-titration from 5 to 40 mg b.i.d. from day D01 to D19; investigational treatments (40 mg DHEC b.i.d. by means of formulation R and T) were administered on day D20 and D21 according to a randomised, period-balanced within-subject cross-over; treatment with DHEC was down-titrated in stepwise fashion from day D22 to D34. Morning doses of 2 x 20 mg DHEC (reference) yielded a fast and relatively short lasting peak with a geometric mean Cmax of 2157 pg/mL (CV: 0.978) after a median tmax of 1.00 h. Cmin throughout the first 12 h was on average 189 pg/mL (CV: 0.908). There was a quite distinct diurnal effect: evening doses of 2 x 20 mg DHEC (treatment R), yielded a relatively lower exposure with geometric mean Cmax, Cav- and Cmin-values of 800 pg/mL (CV: 0.870), 389 pg/mL (0.813) and 177 pg/mL (CV: 0.942). In contrast, there was relatively little within-subject distinction between the two formulations: for the day profile after the morning dose, the estimated ratios of the true means (Pr:R) for Cmax Cmin and Cav were 1.18 (90% CI: 0.96 to 1.43 - CVm: 0.394), 0.96 (90% CI: 0.86 to 1.09 - CVm: 0.230) and 1.06 (90% CI: 0.93 to 1.21 - CVm: 0.254); for the night profile after the evening dose, the estimated ratio of the true means (muT:muR) for Cmax, Cmin and Cav were 1.11 (90% CI: 0.91 to 1.35 - CVm: 0.395), 1.07 (90% CI: 0.95 to 1.20 - CVm: 0.232) and 1.07 (90% CI: 0.95 to 1.20 - CVm: 0.220). In view of important medical-ethical constraints not to expose an unreasonably high number of subjects, these findings could be accepted as a sufficient demonstration of bioequivalence.

Alpha-dihydroergocryptine in the long-term therapy of Parkinson's disease.

The trial was designed as an open-label, post-authorisation safety study, aimed to complete the available information on adverse events and drug reactions to alpha-dihydroergocryptine (CAS 14271-05-7, alpha-DHEC). The study included 294 patients with idiopathic Parkinson's disease who received levodopa (CAS 59-92-7, L-DOPA) and started taking alpha-DHEC (Cripar). Adverse events were analysed descriptively, Parkinson's disease symptoms were documented using a questionnaire applied by the physicians. Patients were evaluated at study start and three and six months later, respectively. In 31 patients, 32 adverse events were observed, gastrointestinal and nervous system disorders being the most frequent. Dyskinesias, psychoses/hallucinations, sleep disturbances, and cardiovascular disorders were uncommon (< or = 1%). in total, 21 adverse events were classified as adverse drug reactions. In nearly 80 % of the cases, Parkinson symptoms had improved or completely vanished. Symptoms were unchanged in 16.7 % of patients and had worsened in 3.1%. The results confirm that the use of alpha-DHEC in combination therapy with levodopa in patients with Parkinson's disease is a well-tolerated and efficacious treatment option.