Unexpected drug-induced Raynaud phenomenon: Analysis from the French national pharmacovigilance database.

OBJECTIVE: To estimate the association between exposure to medicinal products and Raynaud phenomenon. METHODS: The study used the data of all adverse drug reactions notified to the French national pharmacovigilance database. All cases reported between 1st January 1995 and 10th December 2012 were selected. A case/non-case method was used to measure disproportionality of the association between drug exposure and Raynaud phenomenon. The cases concerned all observations involving Raynaud phenomenon. Non-cases comprised all other reports of adverse drug reactions over the same period. RESULTS/DISCUSSION: Among the 307,128 adverse drug reaction reports selected from the French national pharmacovigilance database, 175 involved Raynaud phenomenon, most of them affecting women (61.1%). The mean age was 50.1 years, and 8% had a past medical history of Raynaud phenomenon. According to the summaries of product characteristics, 42.3% of these cases were exposed to drugs known to induce Raynaud phenomenon. Unexpected Raynaud phenomenons (unlisted in the summaries of product characteristics) were associated with exposure to drugs for which Raynaud phenomenons are published (interferons, ribavirin, gemcitabine) or for which Raynaud phenomenons are not published (hepatitis B vaccine, isotretinoin, leflunomide, hydroxycarbamide, rofecoxib, telmisartan, zolmitriptan). CONCLUSION: The case/non-case method is usually used to generate signals. Further epidemiological studies are now necessary to confirm these findings.

A non-pharmaceutical form of Artemisia annua is not effective in preventing Plasmodium falciparum malaria.

Non-pharmaceutical forms of Artemisia annua (a Chinese plant containing artemisinin) are used by some travellers who believe these products are safer than anti-malarial drugs. We report two cases of severe Plasmodium falciparum malaria requiring hospitalization in an Intensive Care Unit following prophylaxis with non-pharmaceutical A. annua in French travellers.

[Pregnancy outcome after preconceptional exposure to methotrexate for ectopic pregnancy]. / Méthotrexate pour grossesse extra-utérine : quels risques en cas de nouvelle grossesse ?

INTRODUCTION: Methotrexate (MTX) is a known teratogenic drug used off-label in the treatment of ectopic pregnancies (EP). As MTX polyglutamated derivatives remains into the cells during several weeks, it is recommended to avoid conception during 3 to 6 months following MTX therapy. We report the follow-up of pregnancies after preconceptional exposure to MTX for EP. MATERIAL/METHODS: Prospective cases of pregnancy occurring within 3 months after MTX injection for an EP recorded in the Terappel database were analyzed. RESULTS: Data were obtained on 52 pregnant women. The median age of patients was 28 (18-38), and the median gestational age at inclusion was 7 weeks after last menstrual period (3-22). The time between the last MTX injection and conception ranged from 12 days to 13 weeks and the total MTX dose was between 40 to 210mg. Out of 45 pregnancies with known outcome, there were 39 live births (87%), 3 spontaneous abortions (6.7%) occurring 63 to 94 days after MTX administration, 2 elective terminations, and 1 medical termination after premature rupture of membranes, oligohydramnios and arthrogryposis (48mg of MTX 9 and 8 weeks before conception). Two additional cases of major malformations were observed among 40 examinable babies or fetuses: tetralogy of Fallot (MTX 6 weeks before conception), and cerebral ventriculomegaly with normal karyotype (50mg of MTX 9 to 13 weeks before conception). The resulting rate of major malformations was 7.5% (95% CI: 1.6-20.4). DISCUSSION/CONCLUSION: Although this prospective study shows a major malformation rate higher than expected in the general population, the observed malformations are not consistent with the typical pattern of methotrexate embryopathy. However, the case of tetralogy of Fallot is reminiscent of previously published cases with MTX exposure during early pregnancy. Owing to the small sample size, more powerful studies are needed to confirm or refute these findings.

Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient.

Suspicion of fenofibrate-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a case report.

We describe a DRESS syndrome induced by fenofibrate. This side effect, rarely described with fenofibrate, should be known by clinicians to stop it immediately and avoid serious complications.

Study of the use of a spironolactone and angiotensin-converting enzyme inhibitor combination: a population-based analysis.

PURPOSE: To analyse the conditions of use of the drug combination in outpatients. METHODOLOGY: The first section consisted of a population-based analysis using computerized records from the French national health insurance system. The study population consisted of adult patients, receiving long-term treatment with spironolactone (SPIR) and angiotensin-converting enzyme inhibitor (ACEI). For each patient, the reimbursement of serum potassium and creatinine determinations was searched for in the database during the 6-month period preceding the date of the last dispensation. The second section comprised a written questionnaire on use practises, sent to practitioners who prescribed the drug combination to randomly selected patients. Analysis of the answers to the questionnaire made it necessary to develop a reference system. In the third section, procedure one was repeated at a later stage, following an information campaign, in order to measure its impact. RESULTS: The exhaustive population under procedure 1 consisted of 3620 patients (71 +/- 11 years). During the 6 months prior to the index date, 51% of patients underwent at least one determination of both serum potassium and serum creatinine. The randomised population under procedure two consisted of 441 patients (70 +/- 13 years) and their 375 practitioners. When compared with the reference system, SPIR-ACEI was used for the recommended indications, at the appropriate SPIR-ACEI dosages, and under minimal monitoring of biological parameters in only 65 patients (15%). After the information campaign, results were disappointing because only 55% of patients underwent the minimal laboratory monitoring. CONCLUSION: The use of the drug combination in general practice was mainly inappropriate.

[Prospective observational study of drug-induced hyperkalemia in hospitalized non dialized adult patients]. / Etude prospective observationnelle des hyperkaliémies médicamenteuses chez des adultes non dialysés hospitalisés.

OBJECTIVE: To study the incidence and risk factors of drug-induced hyperkalemia in adult, hospitalized patients. METHODOLOGY: A three months prospective observational study was used including all hospitalized, non dialyzed, patients older than 17 years who presented with a hyperkalemia egal or over 6 mmol/L. The studied variables were demographic, clinical, biological and therapeutic. RESULTS: Forty patients, among 112 included, had a hyperkalemia promoted by drug(s) (3.5 cases for 1000 hospitalized patients). They were 73 +/- 15 years old and 72.5% had a past medical history of chronic renal failure. The hyperkalemia (6.42 +/- 0.48 mmol/L) was associated with an increase in creatininemia in 67.5% of patients. The most frequent treatment observed were renin angiotensin system drugs in 62.5% of patients, spironolactone in 37.5% or both drugs in 25%. CONCLUSION: A better use of these drugs would be able to prevent some cases of hyperkalemia.

[How practitioners view generic drugs: an opinion study from general practitioners in Maine-et-Loire (France)]. / Medicaments génériques, le point de vue des médecins : enquête d'opinion réalisée auprès des médecins libéraux du Maine-et-Loire.

INTRODUCTION: Generic drugs are copies of original drugs, hence their low cost. In France, expansion of the use of generic drugs is not significant and the support of practitioners is essential in increasing this. AIM: The purpose of this study was to survey the opinion and practical experience of physicians regarding generic drugs, in order to develop a proposal for the safer use of these drugs. METHODS: A form was sent to the 1235 general and specialist practitioners in the Maine-et-Loire "département" with assistance from the regional health insurance, in March 2002. The main topics studied were prescribing practices, risks associated with generic drugs and pharmacist substitutions. The chi2 test and Fisher's exact test were used in the data analysis. RESULTS: Four hundred and twenty-nine forms were returned (34.7%). Only 55% of practitioners considered generic drugs to be as safe and effective as original drugs. Fifty-nine percent prescribe generics rarely or never. The prescribing depends on many factors, linked to the practitioner, the patient or the drug. Many practitioners reported adverse events with generic medicines. With regard to the switch by the pharmacist, it was reported that 45% of prescribers would refuse it in some instances. Among the proposals, cooperation between practitioners and pharmacists in the choice of the generic drugs was approved by 57% of physicians. DISCUSSION: The main perception is that the vastness of the generic world and the fear of adverse events are somewhat bewildering for both patients and health professionals. Among the proposals made by practitioners, a decrease in the number of generics for a same molecule and the institution of a standard price are widely approved. CONCLUSION: Practitioners do not refuse to use generic drugs but are very concerned about the risks of adverse effects for their patients. They regard it as important that a patient receiving chronic treatment be given the same generic drug each time.