Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add-on therapy in epileptic children

1 Lamotrigine is a new antiepileptic drug, chemically unrelated to currently used antiepileptic medication. Its pharmacokinetics can be influenced by concomitant antiepileptic medication

Avis relatif aux masques dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 en rapport avec l'émergence du variant Omicron (HCSP, Avis et Rapports)

International audienceAvis relatif aux masques dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 en rapport avec l'émergence du variant Omicron (HCSP, Avis et Rapports)Ch. Chidiac, J.-F. Gehanno, B. Pozzetto, N. Vernazza, S. Aho-Glele, D. Lepelletier, J.-M. Brignon, E. Gehin, P. Hartemann, Y. Lévi, F. Marano, J.-L. Roubaty, F. Squinazi, A. Billette de Villemeur, A. Berger-Carbonne, É. Gaffet, B. Moltrecht, G. Salvat, S. Van Der Werf, F. Eker, A. Pariente-Khayat, S. Urban-BoudjelabEditeur : Haut Conseil de la Santé PubliqueDate du document : 23 Décembre 2021Date de mise en ligne : 2 Février 2022 (33 pages)https://www.hcsp.fr/Explore.cgi/AvisRapportsDomaine?clefr=1147Le HCSP examine dans cet avis les stratégies d’indications du port des appareils de protection respiratoire (APR) de type FFP2 en population générale ou à risque, dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 dans le contexte d’émergence du variant Omicron.Il précise, dans un complément au DGS le 7 janvier 2022, actualisé le 15 janvier 2022, que le port correct des APR de type FFP2.Le HCSP rappelle que :-L’efficacité et la performance de protection (filtration) des masques, quels qu’ils soient, sont étroitement dépendantes de la constance du port, de l’ajustement au visage et de la qualité du port couvrant impérativement le nez, la bouche et le menton ;--Le masque ne peut à lui seul réduire le risque de transmission ; il constitue une mesure parmi l’ensemble des mesures de protection à respecter (vaccination, hygiène des mains, ventilation des locaux, distanciation sociale, etc.).Le HCSP souligne les fortes incertitudes et manques de données scientifiques sur plusieurs aspects importants de l’analyse du rapport bénéfices/risques en faveur d’un élargissement du port d’APR de type FFP2 en population générale.Le HCSP définit 4 scenarii possibles relatifs aux indications du port d’APR de type FFP2 en population générale.Dans un complément au DGS le 7 janvier 2022, actualisé le 15 janvier 2022, il précise que le port correct des APR de type FFP2 en population générale peut trouver des indications chez les personnes à risque de formes graves de Covid-19 et en échec de vaccination par immunosuppression, et en capacité de le supporter, sur consultation médicale. Cette recommandation doit s’accompagner de formations spécifiques sur les caractéristiques, les performances et le port correct d’APR FFP2 notamment l’adaptation à la taille et à la morphologie du visage pour les personnes concernées.Le HCSP précise également, à cette occasion, ses recommandations concernant le milieu scolaire et universitaire.Ce document est complémenté par :Appareils de protection respiratoire de type FFP2 en population générale dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 en rapport avec l'émergence du variant Omicron (complément) du 7 janvier 2022Lire aussi dans les avis et rapports :Coronavirus SARS-CoV-2 : Rationalisation de l’utilisation des masques respiratoires pour les professionnels de santé en période épidémique du 10 mars 2020Covid-19 : actualisation de la liste des facteurs de risque de forme grave du 29 octobre 2020Masques dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 du 29 octobre 2020Covid-19 : avis sur le protocole sanitaire renforcé proposé pour les commerces du 22 novembre 2020Covid-19 : Risque de transmission du SARS-CoV-2 par aérosols en milieux de soins du 10 septembre 2020Covid-19 : contrôle de la diffusion des nouveaux variants du virus du 14 janvier 2021Covid-19 : stratégie pour la définition de mesures permettant la réouverture des établissements recevant du public du 18 avril 2021Stratégie à adopter pour le stock de l’État en masques et équipements de protection individuelle du 6 août 2021Appareils de protection respiratoire de type FFP2 par les professionnels de santé dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 en rapport avec l'émergence du variant Omicron (complément) du 7 janvier 2022Lire aussi :Masques de protection respiratoire et risques biologiques : foire aux question

FFP2 respiratory protective devices in the general population to fight against the spread of the SARS-CoV-2 virus in relation to the emergence of the Omicron variant (HCSP, Avis et Rapports)

International audienceFFP2 respiratory protective devices in the general population to fight against the spread of the SARS-CoV-2 virus in relation to the emergence of the Omicron variantIn this statement, the French High Council for Public Health or HCSP examines the strategies for indicating the use of FFP2-type respirator protective devices (RPE) in the general population or in populations at risk, as part of the fight against the spread of the SARS-CoV-2 virus in the context of the emergence of the Omicron variant.It specifies, in a supplement sent to the Directorate-General for Health (DGS) on 7 January 2022, (updated on 15 January 2022), that the correct wearing of FFP2-type respirators is essential.The HCSP takes into account that :The effectiveness and protective performance (filtration) of masks, whatever they may be, are closely dependent on the constancy of wear, the fit to the face and the quality of wear covering the nose, mouth and chin imperatively;The mask alone cannot completely stop the risk of transmission; it is one of the protective measures to be respected (vaccination, hand hygiene, ventilation of premises, social distancing, etc.).The HCSP stresses the high level of uncertainty and lack of scientific data on several important aspects of the analysis of the benefit/risk ratio in favour of extending the use of FFP2-type respirators in the general population.The HCSP defines 4 possible scenarios relating to the indications for wearing FFP2-type respirators in the general population.In a supplement sent to the DGS on 7 January 2022, (updated on 15 January 2022), it specifies that the correct wearing of FFP2 type respirators in the general population may be indicated for people at risk of severe forms of Covid-19 and who have failed immunosuppression vaccination, and who are able to tolerate it, on medical advice. This recommendation must be accompanied by specific training on the characteristics, performance and correct wearing of FFP2-type respirators, in particular the adaptation to the size and morphology of the face of the persons concerned.The HCSP also specifies, on this occasion, its recommendations concerning the school and university environment.Lire en français :Appareils de protection respiratoire de type FFP2 en population générale dans le cadre de la lutte contre la propagation du virus SARS-CoV-2 en rapport avec l'émergence du variant Omicron du 23 décembre 202

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses.

OBJECTIVES: To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. PATIENTS AND METHODS: We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. RESULTS: The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. CONCLUSIONS: Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing

Pharmacokinetics of Isoniazid, Rifampin, and Pyrazinamide in Children Younger than Two Years of Age with Tuberculosis: Evidence for Implementation of Revised World Health Organization Recommendations▿

The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dosage recommendations for children. No pharmacokinetic studies for these revised dosages are available for children <2 years. The aim of the study was to document the pharmacokinetics of the first-line anti-TB agents in children <2 years of age comparing previous and revised WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus 15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate the effects of clinical covariates, including HIV coinfection, nutritional status, age, gender, and type of tuberculosis (TB), and the effect of NAT2 acetylator status. Serum INH, PZA, and RMP levels were prospectively assessed in 20 children <2 years of age treated for TB following the previous and the revised WHO dosage recommendations. Samples were taken prior to dosing and at 0.5, 1.5, 3, and 5 h following dosing. The maximum drug concentration in serum (Cmax), the time to Cmax (tmax), and the area under the concentration-time curve (AUC) were calculated. Eleven children had pulmonary and 9 had extrapulmonary TB. Five were HIV infected. The mean Cmax (μg/ml) following the administration of previous/revised dosages were as follows: INH, 3.19/8.11; RMP, 6.36/11.69; PZA, 29.94/47.11. The mean AUC (μg·h/ml) were as follows: INH, 8.09/20.36; RMP, 17.78/36.95; PZA, 118.0/175.2. The mean Cmax and AUC differed significantly between doses. There was no difference in the tmax values achieved. Children less than 2 years of age achieve target concentrations of first-line anti-TB agents using revised WHO dosage recommendations. Our data provided supportive evidence for the implementation of the revised WHO guidelines for first-line anti-TB therapy in young children