ABSTRACT
AIM: Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy. METHODS: This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes. RESULTS: The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose. CONCLUSION: Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.
Subject(s)
Anticonvulsants/administration & dosage , Anticonvulsants/pharmacokinetics , Epilepsy/drug therapy , Valproic Acid/administration & dosage , Valproic Acid/pharmacokinetics , Adolescent , Adult , Age Factors , Anticonvulsants/blood , Child , Child, Preschool , Drug Interactions , Drug Monitoring , Drug Therapy, Combination , Enzyme Activators/administration & dosage , Enzyme Activators/blood , Enzyme Activators/pharmacokinetics , Epilepsy/metabolism , Female , Humans , Male , Middle Aged , Polypharmacy , Retrospective Studies , Valproic Acid/blood , Young AdultABSTRACT
INTRODUCTION: Valproic acid (VPA) is an anticonvulsivant drug widely prescribed in the treatment of many forms of generalized epilepsy. In literature, the incidence of liver damage induced by AVP is 0.01%. It is potentialized by the combination therapy (phenobarbital, carbamazepine). Severe hepatotoxicity is rare and appears to be independent of dose and to cause a high mortality. METHODS: The aim of our study was to evaluate the relationship between plasma concentrations of AVP and the occurrence of side effects especially hepatotoxicity in patients receiving high doses of AVP. RESULTS: In this period, 425 plasmatic AVP monitoring were carried out in our laboratory. From 128 patients treated by high doses of AVP, only 73 were included in this study. Our work showed that adverse effects in epileptics under high doses of AVP was related to the association of the AVP with other antiepileptic in particular carbamazépine, phenobarbital and benzodiazepines rather than supra-therapeutic plasmatic concentrations of AVP. The association of AVP to major antiepileptics (carbamazépine and or phenobarbital) does not seem to generate an increase in the plasmatic concentration of AVP, which was not associated with a greater risque of adverse effects. CONCLUSION: Consequently, clinical signs of liver toxicity may be present in AVP concentrations generally considered in the therapeutic range especially when used in high doses and or combined with antiepileptic drugs like phenobarbital or carbamazepine.
Subject(s)
Anticonvulsants/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Valproic Acid/adverse effects , Adolescent , Adult , Aged , Anticonvulsants/administration & dosage , Anticonvulsants/blood , Bilirubin/blood , Carbamazepine/adverse effects , Chemical and Drug Induced Liver Injury/epidemiology , Dose-Response Relationship, Drug , Drug Interactions , Drug Monitoring , Epilepsy/complications , Epilepsy/drug therapy , Female , Humans , Infant , Liver Function Tests , Male , Middle Aged , Phenobarbital/adverse effects , Risk Assessment , Valproic Acid/administration & dosage , Valproic Acid/blood , Young AdultABSTRACT
Les effets indesirables aux antibiotiques constituent un reel probleme de sante publique. Dans ce travail; ont ete analyses la frequence; les types; les facteurs predisposant et la gravite des effets indesirables aux antibiotiques. Notre etude; de type retrospectif; porte sur les cas d'effets indesirables aux antibiotiques obtenus par notification spontanee au centre regional de pharmacovigilance de Sfax durant une periode de trois ans. Parmi 249 cas d'effets indesirables medicamenteux; 82 cas (32;93) ont ete lies aux antibiotiques. L'age variait de 5 a 86 ans. Il s'agissait de 55 femmes et de 27 hommes. Soixante dix effets indesirables lies aux antibiotiques (85.36) parmi 82 etaient de nature immunoallergique. Dans 60 cas (73.17); les patients avaient des antecedents medicaux: atopie; allergie medicamenteuse; maladies auto-immunes ou pathologies chroniques necessitant une polymedication. 54 patients (65.85) prenaient 3 medicaments ou plus. Les formes graves ont ete observees chez 12 patients parmi 82 (14.63). La polytherapie; les maladies chroniques et l'age avance sont des facteurs favorisant la survenue des effets indesirables aux antibiotiques. Nos resultats soulignent le risque augmente chez les sujets ayant un antecedent d'allergie a un antibiotique de developper une allergie a un autre antibiotique