[Drug-induced pancreatitis. A review of French spontaneous reports]. / Pancréatites d'origine médicamenteuse. Revue des notifications spontanées en France.

PURPOSE: Identify the main pharmacological classes inducing pancreatitis using spontaneous reports recorded in the French pharmacovigilance database (FPVD). METHODS: Cases of pancreatitis recorded in FPVD between January 1st 1985 and December 31st 2013 were selected using the 2001 consensus conference criteria of the French High Health Authority. RESULTS: During this period, 2975 observations were selected with 1151 fulfilling criteria of drug-induced pancreatitis (i.e. 0.22% of total notifications in the FPVD). According to ATC classification, the pharmacological classes most frequently found were antiretroviral, analgesic, lipid-lowering, immunosuppressive and insulin secreting drugs. For some drugs (metformin, omeprazole, etc.) pancreatitis was "unlabelled" in the summary of product characteristics. CONCLUSION: This review allows to identify the main drug classes currently involved in spontaneous reporting of pancreatitis in France.

Birth defects observed with maternal carbimazole treatment: Six cases reported to Nice's Pharmacovigilance Center.

GOALS: To report cases of embryopathy occurring following first trimester exposure to anti-thyroid drugs. METHODS: Retrospective screening of the database of our Pharmacovigilance Center from 1987 to date. RESULTS: We report six cases of embryopathy, all following carbimazole exposure during the first trimester: two cases of abdominal wall defect, including one associated with facial dysmorphia; one case of digestive malformation (patent omphalomesenteric duct); two cases of aplasia cutis including one with facial dysmorphism; one case of bilateral choanal atresia with aorta coarctation associated with poorly controlled insulin dependent diabetes. Four out of five patients were euthyroid with treatment during the first trimester. We found a context suggesting genetic predisposition to congenital malformation in three cases: two cases of parental cleft lip/palate, one case of consanguinity. Outcome was favorable in all cases. CONCLUSIONS: We want to raise awareness about the potential teratogenicity of carbimazole, probably on a predisposed genetic background. We suggest better reporting of congenital anomalies in children of women with Graves'disease, with or without in utero exposure to anti-thyroid drugs. In light of current literature, propylthiouracil should be the first line treatment for hyperthyroid women wishing a pregnancy.

[Treatment of clozapine-induced granulocytopenia with lithium (two observations)]. / Correction par le lithium des neutropénies induites par la clozapine (deux cas).

Despite the availability of new treatments, the antipsychotic effectiveness of clozapine has not been matched yet. Unfortunately, its regulation is limited by the side effects. The most detrimental is the hematologic toxicity (neutropenia and agranulocytosis) which requires a regular biological monitoring. Treatment with clozapine must be stopped in those cases of secondary granulocytopenia for about 3% of the patients. The current psychiatric drug lithium carbonate has an opposite effect: it can induce leukocytosis. Thus, lithium carbonate is administered in leukopenia, as well as in many hematologic and immunological diseases. However, few teams have used lithium in order to alleviate clozapine-induced granulocytopenia. We report here 2 patients who developed severe neutropenia (neutrophil count<1.5 yen 10 (9)/L) and for whom the use of lithium enabled us to continue the treatment by clozapine. The first patient had a granulocyte rate constitutionally low which rapidly decreased with clozapine. Thanks to the administration of lithium, he recovered quickly a normal blood cell count, which in fact was much higher than his normal rate. According to our research, it's the first time that lithium is reported to be so efficacious in a patient with such a low rate of granulocytes before treatment. It may be that clozapine is not used for those kinds of patients. The second patient developed granulocytopenia after one year of treatment with clozapine. The use of lithium increased so much the number of granulocytes that we continued the treatment with clozapine alone. After 4 months, there is no reappearance of granulocytopenia. We must take into account the partial and contradictory reports in the literature. However, if this result is confirmed, it could be of a high interest to extend the prescription of clozapine, the most effective current antipsychotic drug.

Severe oral ulcerations induced by alendronate.

The authors report the case of a 54-year-old man suffering from steroid-induced osteoporosis, who presented with severe oral ulcerations due to sucking alendronate tablets instead of swallowing them. The misuse of alendronate in this case, underlies the risk of direct mucosal injury with this drug.

[Pharmacovigilance in practice]. / La pharmacovigilance en pratique.

Directed by the French Agency for the Safety of Health Products (AFSSAPS), the French pharmacovigilance system is in charge of the surveillance of drugs after they have been provided by AFSSAPS with official marketing authorizations that are in France either 'new drug approval certificates' (AMM) or 'temporary utilization authorizations' (ATU). About 3,700 pharmaceutical products are concerned which are used either for treatment (all drugs and remedies, inclusive plasma-derived blood products), prevention (vaccines, oral contraception), diagnosis (contrast products, ...), or to modify a physiologic function (general or local anesthetics). At the national level, the main actors of the system are AFSSAPS and its National Commission, the 31 Regional Centers of Pharmacovigilance, all the health professionnals, and the pharmaceutical laboratories. Health professionnals are held to notify any suspected serious or unexpected adverse effects as quickly as possible. The analysis of data collected by the national report bank permits alerts and inquiries about drug safety. Furthermore regional centers of pharmacovigilance are responsible for drug information. The French pharmacovigilance system works in cooperation with the European Agency for the Evaluation of Medicinal Products.

[Risk related to withdrawal from non-psychotropic drugs]. / Risques liés à l'arrêt des médicaments non psychotropes.

A review of the available literature concerning sudden withdrawal of drugs shows that withdrawal syndrome have occurred with centrally antihypertensive drugs, beta-blockers on anginal patients, antiparkinsonian drugs and glucocorticoids. Because of a lack of controlled trials led among a large number of individuals, the correct frequency of this withdrawal syndrome is unknown. In most patients, it's hard to distinguish a return to a previous state from an overshoot phenomenon. In that way, gradual and supervised withdrawal of these agents should prevent the complication of sudden cessation of these therapy.

[Severe colectasy in rheumatoid purpura. Probable role of water soluble contrast products]. / Colectasie grave au cours d'un purpura rhumatoïde. Rôle probable des produits de contraste hydrosolubles.

BACKGROUND: About 60-70% of cases of anaphylactoid purpura suffer from abdominal colic, which may be quite severe. Because severe abdominal pain may be difficult to differentiate from a surgical abdomen, repeated examination and radiological studies are often necessary. CASE REPORT: A 4 year 7 month-old girl suffered from abdominal pain, vomiting and the skin rash characteristic of anaphylactoid purpura. Because of worsening of the abdominal manifestations, a Gastrografin enema was given. The result was normal but 48 hours later, the child suffered from acute abdominal colics plus symptoms of shock. X-ray examination revealed a large distension of colon and persistence of the contrast material. Exploratory laparotomy failed to find any perforation or necrosis. The colon was drained and the child was given parenteral nutrition and antibiotics. Blood culture showed Klebsiella pneumoniae. An upper gastrointestinal roentgenogram using meglumine ioxitalamate was performed 19 days later because of recurrence of the abdominal pain. This showed a submucosal hemorrhage in the first small bowel loop. Increased abdominal distension occurred 3 days later and the results of X-rays were similar to those seen the Gastrografin enema. A second enema using meglumine ioxitalamate was performed 3 days later. It showed sigmoid constriction but a second laparotomy failed to confirm this obstruction. The child died a few hours later despite ileostomy and antibiotics. CONCLUSIONS: The severe colectasy seen in this case of anaphylactoid purpura indicates that caution is required in performing enemas in acute digestive complications of this disease. Such X-ray studies should not be repeated and all water-soluble contrast material should be voided as soon as possible.

[Economic impact of adverse drug effects. Some reflections]. / Impact économique des effets indésirables des médicaments. Quelques réflexions.

The cost of adverse drug effects first began to be analyzed in the 1960s, with an evaluation of related admissions to hospital in the USA. The average cost per patient of adverse events requiring hospitalization in France was estimated at 6,250 F in neurology units in 1979/1980, and 14,920 F in geriatric units in 1984. Fifty per cent of these events were avoidable. A second approach is to measure the cost of certain iatrogenic manifestations, e.g. fever due to fipexide, stenosis and perforation of the small intestine due to potassium chloride, gastrointestinal bleeding due to NSAIDs, kidney damage due to aminosides, etc. Calculations of the economic impact of adverse drug effects must also take into account indirect costs such as loss of productivity. The lack of such studies should not make health care specialists forget the magnitude of the problem.

[Thrombopenia due to pefloxacin (Peflacine): dose-dependent toxicity?]. / Thrombopénies dues à la péfloxacine (Péflacine): une toxicité dose-dépendante?

Pefloxacin (Peflacine) can give rise to thrombocytopenia, although the responsibility of the drug can be difficult to demonstrate in infectious patients and those receiving other drugs simultaneously. We have collated 18 cases in which the responsibility of pefloxacin was suspected. In 13 cases, the patients were also taking other drugs which may have been contributory (heparin, Bactrim, Augmentin, ranitidine,...). The remaining five cases were of particular interest as pefloxacin was the only drug administered. The mean age of the patients was 75 years, and the mean bodyweight 56 kg (range, 47-65 kg). The pefloxacin dosage was 800 to 1,600 mg/day i.v. or p.o., i.e. 13-18 mg/kg/day. Thrombocytopenia occurred from five to 19 days after beginning treatment and resolved between 7 and 12 days after drug withdrawal. A number of factors argue in favor of dose dependency: 1 patient had high plasma concentrations (peak and residual); thrombocytopenia occurred in one patient when the previous, well-tolerated dosage of 800 mg/day (for 15 days) was increased to 1,600 mg/day; thrombocytopenia resolved in one patient when the dosage was reduced to 400 mg/day (1 tablet) and continued for a further 10 days. This toxic reaction may be avoided by reducing the drug dosage to 400 mg/day in elderly patients with a low bodyweight. Differential blood counts appear to be warranted for patients at risk.