[Pharmacovigilance off the beaten track: herbal surveillance or pharmacovigilance of medicinal plants]. / Une pharmacovigilance hors des sentiers battus: la phytovigilance où la pharmacovigilance des plantes médicinales.

For several years, herbal medicines have been increasingly consumed by patients without prescription. They are traditionally innocuous but as medicinal products they require drug surveillance in order to identify their risks. However, the first concern is to give them a legal status, to evaluate their efficacy and to control their safety. Published data show that the risk is due either to a contaminant or to an added drug or falsification. Since 1985, the Regional Pharmacovigilance Centres have received about 341 reports of undesirable effects due to herbal medicines: among them 30 cases of hepatitis were reported associated with germander which has been now withdrawn from the French market. This example well illustrates the role of the national system and its responsibility for collecting and evaluating ADRs due to herbal medicines.

[Clomiphene-exposed pregnancies--analysis of 39 information requests including 25 cases with known outcome]. / Grossesses exposées au clomifène--analyse de 39 demandes de renseignements dont 25 dossiers avec évolution connue.

With the up to date published data, the risk of clomiphene exposure during pregnancy cannot be determined. After a review of animal experimentation results, we will discuss the human data. Most of the publications with human exposition concern treatments given before the beginning of pregnancy. The questions addressed to the Centre de Pharmacovigilance of Paris F. Widal will be detailed. From May 1983 to July 1995 39 requests are available with only 25 cases of known outcomes. For these 25 cases, five elective terminations and three spontaneous abortions are reported. Only one defect was observed among the 17 births (9 females, 8 males): unilateral fibula agenesis the imputability of which is difficult to establish. These data seems reassuring; however, the number of patients studied is small. Other studies on clomiphene-exposed pregnancies are necessary in order to investigate this risk.

Paraquat poisoning by skin absorption: report of two cases.

Two cases of paraquat poisoning resulting from skin absorption are reported. One patient died from respiratory failure 26 d after deliberate application of the herbicide onto his whole body as a treatment for scabies. The other patient developed extensive dermatitis (probably a complication of pre-existing psoriasis). Only a moderate and transitory impairment of this latter patient's renal and respiratory functions were observed after repeated exposure of his damaged skin to a dilute paraquat spray.

Acute zolpidem poisoning--analysis of 344 cases.

Zolpidem is a new short acting hypnotic agent, first launched in France in 1988. Three hundred forty-four cases of intentional acute overdoses are reviewed retrospectively. Patients were predominantly female (70%) in their third or fourth decade. Ingested doses of zolpidem ranged between 10 and 1400 mg (one pack or less in 80%). Half of the patients ingested other substances (psychotropic drugs and alcohol) concomitantly. Signs of intoxication were observed in two thirds of the population but could be attributed to zolpidem in only 105 cases: drowsiness (N = 89) occurred at doses of 140 to 440 mg; coma (N = 4) or respiratory failure (N = 1). Other symptoms were rare (excepted vomiting, N = 7). Of the rare electrocardiographic or biological abnormalities, none appeared to be directly related to zolpidem. Therapy for intoxication was usually limited to supportive measures and/or gastric lavage. Symptoms of intoxication rapidly remitted in 91% of cases. Three percent of patients with multiple drug ingestion recovered despite severe complications during intensive care. Fatalities were reported for 6% but could not be directly linked to zolpidem. Previous published reports are confirmed: zolpidem acute overdose is generally benign and requires no specific therapeutic measures.

[Evaluation of unexpected and toxic effects of omeprazole (Mopral) reported to the regional centers of pharmacovigilance during the first 22 postmarketing months]. / Bilan des effets inattendus et toxiques de l'oméprazole (Mopral) rapportés aux centres régionaux de pharmacovigilance, au cours des 22 premiers mois de commercialisation.

Omeprazole has been marketed in France since 1989, for the healing of peptic ulcers, erosive reflux esophagitis and the Zollinger Ellison syndrome. It is a proton pump inhibitor which inhibits the acid secretion in the stomach. In the majority of the clinical trials, omeprazole has been found to be well tolerated: headache, dizziness, skin rash, constipation have just been noted. Since September 1989, 143 adverse reactions have been reported to pharmacovigilance centres and Astra France: 37 neurological and psychiatric side effects, especially confusion in patients with hepatic diseases and/or advanced age; 35 cutaneous reactions, generally rash and urticaria; 22 hematological effects: leucopenia and agranulocytosis have been reported but the relation with omeprazole is very uncertain; 10 gastrointestinal effects, generally diarrhoea, nausea, vomiting and abdominal pain; 8 hepatic disorders, especially moderate elevation of aminotransferases. This study confirms the safety of this drug, during short treatment; the frequency of notified adverse effects is about 1/12 200 treatments of 4 weeks. The ministry of health, has decided, in november 1991, to inform the prescribers of this potential toxicity of omeprazole, particularly, of the risk of confusion, hepatotoxicity and leucopenia.

Acute fluvoxamine poisoning.

A total of 221 cases of deliberate acute overdose with fluvoxamine reported to the Paris Poison Centre, and 78 cases collected by the International Drug Safety Department of Duphar BV were analysed. Other agents, mainly benzodiazepines, neuroleptics, other antidepressants and alcohol, were also taken in 77% of the cases. The acute toxicity that could be attributed to fluvoxamine alone was rarely severe. The symptoms observed were always benign when the dose of fluvoxamine was below 1000 mg and included drowsiness, tremor, nausea, vomiting, abdominal pain, bradycardia and/or anticholinergic effects (dry mouth, mydriasis, sinus tachycardia, urinary retention). Seizures occurred in a few cases after high doses (generally > 1500 mg). Cardiotoxicity was not a serious problem; sinus bradycardia was noted with doses of less than 1000 mg, but was always moderate and required no treatment. Conduction abnormalities were rare.