[Drug interactions with colchicine, are the contraindications well respected? A descriptive study of prescriptions in Brittany based on data from the French National Health Data System]. / Interactions médicamenteuses avec la colchicine, les contre-indications sont-elles bien respectées ? Étude descriptive des prescriptions en Bretagne à partir des données de l'Assurance maladie.

Although the French Health Authority "ANSM" widely informed healthcare professionals about the risk factors for colchicine overdose, its impact and suitable dosages, cases of potentially fatal preventable overdose continue to be reported in France. Using the French National Health Insurance of the Brittany area, we quantified the proportion of prescriptions presenting an absolute drug contraindication (CI) to colchicine (according to the ANSM Drug Interactions "Thesaurus") and its impact in terms of hospitalisation. Between 2013 and 2016, nearly 77,000 patients (mean age, 66±15 years) were reimbursed for at least one colchicine-based drug (Colchimax®, Colchicine Opocalcium®), representing nearly 205,000 prescriptions. General practitioners were the main prescribers (93%). Among the prescriptions, 0.5% had absolute IC with colchicine: in 51% of cases with pristinamycin, followed by azithromycin (15.6%), clarithromycin (15.2%) and roxithromycin (11.9%). In the 15 days following the simultaneous prescription of colchicine and a contraindicated drug, 53 hospital stays were recorded. However, using only the primary diagnosis of hospitalization was not sufficiently relevant to conclude that there was no potential overdose of colchicine. Over the study period, the Thesaurus contained inconsistencies that confused clinicians: mention of absolute IC with colchicine in the "macrolide" and "pristinamycin" sections but not in the sections of 'potent CYP inhibitors' or macrolide class molecules. Overall, very few prescriptions included absolute IC with colchicine. Regular training and information of healthcare professionals remains essential to limit the risk of colchicine overdose and to remind them of the potentially fatal consequences.

Trends in sodium valproate prescriptions among children aged 0 to 14 years between 2010 and 2016: A study based on the French National Health Insurance Database.

PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls. METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016. RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%). CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.

Meta-analysis of interstitial pneumonia in studies evaluating iodine-131-labeled lipiodol for hepatocellular carcinoma using exact likelihood approach.

PURPOSE: Iodine-131-labeled lipiodol is currently licensed for unresectable hepatocellular carcinoma with portal thrombosis. It is thought to be well tolerated. Cases of interstitial pneumonia have been reported, but their frequency (≈2%) has not been well estimated. Quantifying adverse drug event frequency requires an appropriate statistical approach because standard methods are biased. METHODS: To estimate the frequency of interstitial pneumonia in patients with hepatocellular carcinoma receiving iodine-131-labeled lipiodol, we conducted a systematic review of English articles using MEDLINE and EMBASE. All types of articles were considered except case reports. Primary outcome measure was symptomatic interstitial pneumonia based on investigators' judgment. All pooled analyses were based on a random effects meta-analysis model using an exact likelihood approach based on the binomial within-study distribution. RESULTS: Ten studies, including 142 patients, used low activity per dose, ranging from 0.3 to 1.1 GBq. No respiratory adverse event was noticed in these studies. Eighteen studies, including 542 patients, evaluated higher activity per dose, around 2.2 GBq; 24 cases of interstitial pneumonia were reported in these studies. Estimated frequency of interstitial pneumonia was 1.6% (95%CI, 0.4-6.4%) after one high dose and 4.1% (95%CI, 1.0-16.0%) after two or more high doses. CONCLUSIONS: The frequency of interstitial pneumonia appears higher and more precise than previously estimated. The risk appears to be related to the number of injections and the dose level per injection. Generalized linear mixed models using the exact binomial within-study distribution initially described to summarize data on diagnostic evaluation could be relevant for drug-related adverse reaction frequency assessment.

¹³¹I-labeled lipiodol-induced interstitial pneumonia: a series of 15 cases.

BACKGROUND: The drug (131)I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration. METHODS: Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital. RESULTS: From 1994 to 2009, interstitial pneumonia developed in 15 patients following (131)I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second (131)I-labeled lipiodol injection. The median delay between last (131)I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8(+) T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last (131)I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days). CONCLUSIONS: Interstitial pneumonia may be a serious and not uncommon complication of (131)I-labeled lipiodol administration.