BACKGROUND: The European Medicines Agency has recommended a series of restrictions on the use of sodium valproate (valproate) following research linking its exposure in utero to adverse congenital and neurodevelopmental effects in offspring. Recent research has highlighted a potential increased risk of neurodevelopmental disorders in children born to males taking valproate prior to conception. Clinicians and patients require guidance regarding suitable alternatives. AIM: To provide an overview of suitable alternatives to valproate in the management of bipolar disorder. METHOD: A narrative review was conducted. Only medications with an established evidence base in managing different phases of bipolar disorder and endorsed within clinical practice guidelines were considered. Eligible guidelines included those (i) where recommendations were informed by a formal guideline development process and (ii) published in English within the last 15 years. REPROTOX® was chosen as the primary information source regarding reproductive safety of alternative medications. RESULTS: Of all second-generation antipsychotics, quetiapine should be considered a first-line alternative to valproate. Lithium has been associated with an increased risk of cardiac malformations, especially Ebstein anomaly, following in utero exposure. However, given its robust efficacy as an antimanic agent and the absolute risk of cardiac abnormalities being low, it's use can still be considered in individuals of child-bearing potential with appropriate monitoring. Carbamazepine treatment should be avoided due to concerns for teratogenicity. Although considered safe in pregnancy, lamotrigine is largely effective at preventing relapse of bipolar depression. Thus, lamotrigine offers limited clinical utility as an alternative to valproate. CONCLUSION: Specific recommendations are made regarding alternatives to valproate in managing bipolar disorder.
- MeSH
- Antimanic Agents * adverse effects therapeutic use MeSH
- Antipsychotic Agents * adverse effects therapeutic use MeSH
- Bipolar Disorder * drug therapy MeSH
- Valproic Acid * adverse effects therapeutic use MeSH
- Humans MeSH
- Disease Management * MeSH
- Pregnancy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
Farmakologická léčba epilepsie je čím dál složitější, vyžaduje komplexní znalosti a klinickou zkušenost. Až jedna čtvrtina lidí s epilepsií užívá více než jeden protizáchvatový lék, mají časté komorbidity, ale i akutní či chronická interkurentní onemocnění vyžadující podávání dalších léčiv. Farmakokinetické a farmakodynamické lékové interakce jsou zpravidla dobře popsány a informace o nich snadno dohledatelné. Méně víme o aktivním influxním/efluxním transportu léčiv jak v průběhu jejich vstřebávání z gastrointestinálního traktu, tak při jejich přestupu přes hematoencefalickou bariéru. Neurolog potřebuje při volbě kombinace/kombinací protizáchvatových léků a/nebo léčivých přípravků z jiných indikací vědět, zda mezi nimi může dojít ke klinicky významné interakci, jaký je její mechanismus a projevy, jak vysoká je pravděpodobnost, že k ní dojde a jak bude závažná.
Pharmacological treatment of epilepsy is more and more complex, requiring comprehensive knowledge and clinical experience. Up to one-quarter of people with epilepsy take more than one antiseizure medication, and they have frequent comorbidities, as well as acute or chronic intercurrent diseases requiring the administration of other drugs. Pharmacokinetic and pharmacodynamic drug interactions are usually well described and information about them is easy to find. We know less about drugs' active influx/efflux transport both during their absorption from the gastrointestinal tract and their transfer across the blood-brain barrier. When choosing a combination(s) of antiseizure medication and/or drugs for other indications, the neurologist needs to know whether a clinically significant interaction can occur between them, what its mechanism and manifestations are, how high the probability of its occurrence and how severe it will be.
- MeSH
- Anticonvulsants * pharmacokinetics pharmacology classification therapeutic use MeSH
- Epilepsy diagnosis drug therapy MeSH
- Blood-Brain Barrier drug effects MeSH
- Carbamazepine pharmacokinetics pharmacology therapeutic use MeSH
- Valproic Acid pharmacokinetics pharmacology therapeutic use MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Syndrom Dravetové je závažnou vývojovou a epileptickou encefalopatií se začátkem v kojeneckém věku, která se projevuje farmakorezistentní epilepsií a četnými komorbiditami. Typická je provokace záchvatů zvýšenou teplotou. Léčba onemocnění je obtížná. V chronické medikaci by měl být první volbou valproát, dalšími přidanými léky klobazam, stiripentol, fenfluramin, kanabidiol, topiramát. Pacienti musí být vybaveni SOS medikací pro zvládnutí záchvatů v domácím prostředí. V léčbě je nutné se vyhnout blokátorům sodíkových kanálů, aplikace fenytoinu v epileptickém statu je však přípustná. Kromě protizáchvatové léčby je nutné věnovat pozornost i nefarmakologické léčbě komorbidit.
Dravet syndrome is a developmental and epileptic encephalopathy starting in infancy and its main features are drug -resistant epilepsy and several co-morbidities. Seizures are typically provoked by increased temperature. The treatment of Dravet syndrome is challenging. The first antiseizure drug should be valproic acid, while clobazam, stiripentol, fenfluramine, canabidiol or topiramate are usually added later. All the patients must have rescue medication for home management of seizures. Sodium channel blockers should not be used for chronic treatment, but phenytoin can be administered to stop status epilepticus. Non-pharmacological treatment of co-morbidities should be addressed as well.
- Keywords
- stiripentol, fenfluramin,
- MeSH
- Dioxolanes administration & dosage pharmacology therapeutic use MeSH
- Epilepsies, Myoclonic * drug therapy pathology MeSH
- Cannabidiol administration & dosage pharmacology therapeutic use MeSH
- Clobazam administration & dosage pharmacology therapeutic use MeSH
- Comorbidity MeSH
- Valproic Acid administration & dosage pharmacology therapeutic use MeSH
- Humans MeSH
- Selective Serotonin Reuptake Inhibitors administration & dosage pharmacology therapeutic use MeSH
- Topiramate administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
Zásahy do pevných lékových forem (např. drcení či vysypávání obsahu tobolek) je v klinické praxi v lůžkových zdravotnických zařízeních častým jevem. Tyto zásahy jsou u některých léčivých přípravků nevhodné a mohou vést k přímému ohrožení pacienta. Ve sdělení jsou uvedeny příklady dvou pacientů, u nichž tyto nevhodné zásahy vedly k výskytu zdravotních komplikací. V diskuzi jsou navržena opatření, která by mohla vést k minimalizaci rizik plynoucích z těchto zásahů do pevných lékových forem.
Interference in solid dosage forms (e.g., crushing or emptying the contents of capsules) is common in clinical practice in inpatient healthcare settings. These interferences are inappropriate for some medicinal products and may lead to direct patient endangerment. Examples of two patients in whom these inappropriate interventions led to health complications are given in this communication. The measures that could lead to minimising the risks arising from these interventions in solid dosage forms are suggested in the discussion.
- MeSH
- Administration, Oral MeSH
- Dabigatran administration & dosage pharmacology MeSH
- Valproic Acid administration & dosage pharmacology MeSH
- Dosage Forms * MeSH
- Middle Aged MeSH
- Humans MeSH
- Metoprolol administration & dosage pharmacology MeSH
- Off-Label Use classification MeSH
- Patient Harm * classification MeSH
- Aged MeSH
- Drug Administration Routes MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
Zásahy do pevných lékových forem (např. drcení či vysypávání obsahu tobolek) je v klinické praxi v lůžkových zdravotnických zařízeních častým jevem. Tyto zásahy jsou u některých léčivých přípravků nevhodné a mohou vést k přímému ohrožení pacienta. Ve sdělení jsou uvedeny příklady dvou pacientů, u nichž tyto nevhodné zásahy vedly k výskytu zdravotních komplikací. V diskuzi jsou navržena opatření, která by mohla vést k minimalizaci rizik plynoucích z těchto zásahů do pevných lékových forem.
Interference in solid dosage forms (e.g., crushing or emptying the contents of capsules) is common in clinical practice in inpatient healthcare settings. These interferences are inappropriate for some medicinal products and may lead to direct patient endangerment. Examples of two patients in whom these inappropriate interventions led to health complications are given in this communication. The measures that could lead to minimising the risks arising from these interventions in solid dosage forms are suggested in the discussion.
- MeSH
- Administration, Oral MeSH
- Dabigatran administration & dosage pharmacology MeSH
- Valproic Acid administration & dosage pharmacology MeSH
- Dosage Forms * MeSH
- Middle Aged MeSH
- Metoprolol administration & dosage pharmacology MeSH
- Off-Label Use classification MeSH
- Patient Harm * classification MeSH
- Aged MeSH
- Drug Administration Routes MeSH
- Check Tag
- Middle Aged MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- cefepin/enmetazobactam,
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Anticonvulsants classification MeSH
- Autistic Disorder etiology MeSH
- Child MeSH
- Pharmacogenetics methods MeSH
- Fertilization MeSH
- Urinary Tract Infections drug therapy complications MeSH
- Valproic Acid * adverse effects toxicity MeSH
- Medical Informatics MeSH
- Humans MeSH
- Neurodevelopmental Disorders MeSH
- Fathers MeSH
- Pyelonephritis drug therapy MeSH
- Randomized Controlled Trials as Topic MeSH
- Artificial Intelligence * MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
Autism spectrum disorder (ASD) is a psychiatric disorder with severe behavioral consequences and no specific therapy. Its etiology is multifactorial, as it is caused by a complex interaction of genetic and environmental factors. In rats, prenatal exposure to the antiepileptic drug valproic acid (VPA) has been associated with an increased risk of autistic-like behaviors in offspring, including social behavior deficits, increased repetitive behaviors, and cognitive impairments. In addition, VPA-treated rats have shown altered sociosexual behaviors. However, the mechanisms underlying these alterations in reproductive processes in VPA-treated rats are not fully understood. Interestingly some abnormal behaviors in VPA autism models are improved by an enriched environment (EE). In the present study, we examined the effects of EE on memory performance and sexual behavior in male rats. We found that on postnatal day 90, EE reduced the time it took for both control and VPA-treated groups to find a hidden platform in the Morris water maze. On PND 100, prenatal exposure to VPA reduced total exploring time in object recognition tests. On PND 110, EE reduced mount and intromission latency and increased ejaculatory frequency in VPA-treated male rats. These results suggest that environmental stimuli significantly influence the onset of sexual behavior in VPA-treated male rats and that EE may be a potential tool for improving a variety of behavioral deficiencies in rodent models of autism.
- MeSH
- Autistic Disorder * chemically induced MeSH
- Rats MeSH
- Valproic Acid adverse effects MeSH
- Humans MeSH
- Autism Spectrum Disorder * chemically induced MeSH
- Sexual Behavior MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects * chemically induced MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Prevalence lékových interakcí v populaci kriticky nemocných je vysoká, ale často se jedná o potenciální lékové interakce s omezenou klinickou významností. Cílem tohoto sdělení je popsat mechanismus a management nikoliv nejčastějších, ale dle autorů klinicky nejvýznamnějších interakcí. Do přehledu jsme zahrnuli interakci karbapenemů a valproátu, inhibitorů CYP 3A4 a tikagreloru, enterální výživy a levodopy, kombinace léčiv prodlužujících QT interval a inhibitorů CYP 3A4 a kvetiapinu.
The prevalence of drug interactions in the critically ill is high, but these are often potential drug interactions of limited clinical relevance. This paper aims to describe the mechanism and management of not the most frequent but, according to the authors, the most clinically significant interactions. These top five interactions include carbapenems and valproate, CYP 3A4 inhibitors and ticagrelor, enteral nutrition and levodopa, combinations of QT prolonging drugs, and CYP 3A4 inhibitors and quetiapine.
- MeSH
- Enteral Nutrition MeSH
- Cytochrome P-450 CYP3A Inhibitors pharmacology MeSH
- Carbapenems pharmacokinetics pharmacology adverse effects MeSH
- Valproic Acid pharmacokinetics pharmacology MeSH
- Drug Interactions * MeSH
- Levodopa pharmacokinetics pharmacology MeSH
- Humans MeSH
- Drug-Related Side Effects and Adverse Reactions prevention & control MeSH
- Quetiapine Fumarate pharmacology MeSH
- Long QT Syndrome chemically induced etiology MeSH
- Ticagrelor pharmacology adverse effects MeSH
- Check Tag
- Humans MeSH
- Keywords
- epileptická encefalopatie,
- MeSH
- Child MeSH
- Epilepsies, Myoclonic * diagnostic imaging diagnosis drug therapy genetics MeSH
- Drug Therapy, Combination MeSH
- Valproic Acid therapeutic use MeSH
- Lennox Gastaut Syndrome * diagnosis drug therapy genetics MeSH
- Humans MeSH
- Risk Factors MeSH
- Developmental Disabilities diagnosis MeSH
- Check Tag
- Child MeSH
- Humans MeSH
OBJECTIVES: Levetiracetam is an anticonvulsive drug increasingly used in paediatric populations. Ontogenesis may alter its pharmacokinetics, demanding dose individualisation of levetiracetam in paediatric populations. We therefore aimed to explore levetiracetam pharmacokinetics and to propose its optimal dosing in the paediatric population. METHODS: Individual levetiracetam pharmacokinetic parameters were calculated based on therapeutic drug monitoring data, using a one-compartmental model, and regression models were used to explore possible covariates. RESULTS: 56 patients aged from 47 days to 18 years were included in the analysis. The median (IQR) volume of distribution and clearance of levetiracetam were 0.7 (0.58-0.85) L/kg and 0.123 (0.085-0.167) L/hour/kg, respectively. Levetiracetam pharmacokinetics were influenced by postnatal age, body size descriptors and renal functional status. CONCLUSIONS: Based on observed relationships, an individualised loading dose of 26.2 mg/kg body weight and maintenance dose of 20.7 mg/mL/min of estimated glomerular filtration rate were calculated as optimal. Since we observed increased levetiracetam clearance in association with valproate co-medication, caution should be used when combining these two drugs.
- MeSH
- Anticonvulsants * MeSH
- Child MeSH
- Valproic Acid * MeSH
- Levetiracetam MeSH
- Humans MeSH
- Drug Monitoring MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
