Dobrá znalost nežádoucích účinků léčiv (NÚL) je klíčová pro jejich bezpečné používání. NÚL jsou častým klinickým problémem jak u dospělých, tak u pediatrických pacientů. Vyskytují se u více než 9 % hospitalizovaných dětí a jsou důvodem přijetí až ve 4 % případů. Toxicita léčiv může mít v dětství specifický charakter. Zejména novorozenci jsou k jejím projevům náchylnější než jiné věkové kategorie pacientů. Až 70 % léků v pediatrické populaci je předepisováno způsobem, který není schválen regulačními autoritami. Riziko výskytu nežádoucích účinků při tomto podávání je 3,6x vyšší za hospitalizace a 2х vyšší v ambulantní péči. Většina NÚL u dětí je shodná s nežádoucími účinky u dospělých, proto jsou v článku uvedeny pouze nejtypičtější syndromy specifické pro dětský věk – Reyův syndrom, grey syndrom, poruchy růstu kostí, zubů a pojivových tkání, poruchy tělesného růstu, psychiatrické syndromy a další nežádoucí účinky s odlišnými charakteristikami u dětí.

Good knowledge of adverse drug reactions (ADRs) is crucial for safe use of medication. ADRs are a common clinical problem in both pediatric and adult medicine that can lead to significant morbidity. More than 9 % of hospitalized children suffer some adverse reactions to therapy and up to 4 % of all their hospital admissions are caused by ADRs. The toxicity of many medicines in children is different to that seen in adults. Indeed, there are some groups of pediatric patients, such as neonates, in whom drug toxicity appears to be relatively common. About 70 % of drugs prescribed to the pediatric population are prescribed off-label. The risk of adverse drug reactions with such prescribing is 3,6-fold higher in the hospital setting and 2-fold higher in the outpatient setting compared to on-label prescribing. Most of the ADRs in children are similar to ADRs in adults. In this paper, ADRs specific for the pediatric population are discussed: Reye’s syndrome, Gray baby syndrome, quinolone arthropathy, tooth discoloration, growth disorders, psychiatric disorders and others. disorders, psychiatric disorders, acute agitation.

• Klíčová slova
• postanestetický neklid, psychiatrické syndromy, grey syndrom, Reyův syndrom, děti,
• MeSH
• antidepresiva škodlivé účinky   terapeutické užití   MeSH
• bronchiální astma farmakoterapie   MeSH
• chinolony MeSH
• chloramfenikol kontraindikace   škodlivé účinky   toxicita   MeSH
• depresivní poruchy farmakoterapie   MeSH
• dítě MeSH
• fluorochinolony škodlivé účinky   toxicita   MeSH
• glukokortikoidy škodlivé účinky   terapeutické užití   MeSH
• hormony kůry nadledvin škodlivé účinky   MeSH
• kojenec MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• nežádoucí účinky léčiv epidemiologie   prevence a kontrola   MeSH
• novorozenec MeSH
• poruchy růstu chemicky indukované   MeSH
• předškolní dítě MeSH
• Reyeův syndrom etiologie   chemicky indukované   patofyziologie   MeSH
• systémy pro sběr zpráv o nežádoucích účincích léků statistika a číselné údaje   MeSH
• tetracykliny kontraindikace   škodlivé účinky   toxicita   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH

Adverse drug reactions (ADRs) are common problems in both paediatric and adult medicine. The aim of this study was to prospectively identify the ADRs causing hospital admission of children and identification of the risk factors and involved drugs. The study was performed at the University Hospital in Olomouc, Czech Republic. All patients aged 19 years or under admitted to hospital were included in the study, and all admissions for ADRs were prospectively screened for a period of 9 months. Suspected ADRs were subsequently evaluated in detail, and causality assessment was undertaken to determine whether each suspected reaction was possible, probable or definite. The assessment of ADR causality was performed using the Naranjo algorithm, the Liverpool ADR Causality Assessment Tool and the Edwards and Aronson causality assessment method. During the study period, 2903 admissions were identified; of these, there were 143 admissions of patients with an oncological disease. Sixty-four admissions (2.2%) were caused by an ADR. Anticancer chemotherapy accounted for 35% of the cases, followed by antibiotics (18%), immunosuppressants and vaccines (9% each). The use of different scoring systems does not lead to the differences in the numbers of ADR-diagnosed patient but may result in differences in the determination of the level of certainty. ADRs cause a substantial proportion of children's hospital admissions. The majority of the ADR-diagnosed patient affected the hematopoietic and gastrointestinal systems; the drugs most frequently involved were cytotoxic agents and antibiotics. The most important risk factors identified were female sex and oncological disease.

• MeSH
• antibakteriální látky škodlivé účinky   MeSH
• antitumorózní látky škodlivé účinky   MeSH
• dítě MeSH
• hospitalizace statistika a číselné údaje   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• nežádoucí účinky léčiv epidemiologie   etiologie   terapie   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

PURPOSE: Spontaneous reporting systems in European countries are crucial for collecting adverse drug reaction (ADR) reports. The aim of this study was to evaluate reporting activity among countries and their strategy to increase the number of reports. We also established the best measure for assessment quantity of reports. METHODS: This was a retrospective observational study based on questionnaires and annual reports. The most reliable measure of reporting was determined by Spearman correlation coefficients. RESULTS: Data collected in spontaneous reporting systems in 26 European countries were analysed. In 2007, 2008 and 2009, the average value of reports per year per million inhabitants based on the safety databases of countries was 208, 236, 286, respectively; in comparison, that of Eudra- Vigilance was 311, 453 and 435, respectively. Twelve countries reached a significant level for signal detection of ADRs in 2009. The population-based reporting ratio (PBRR) was correlated to the total expenditure on health (ρ=0.499, p=0.023, n=21), public expenditure on health (ρ=0.477, p=0.035, n=20), density of physicians (ρ=0.336, p=0.136, n=21) and expenditure on pharmaceuticals (ρ=0.365, p=0.114, n=20). Strategies of regulatory authorities to increase reporting were determined. CONCLUSIONS: The results of this study make several noteworthy contributions regarding national spontaneous reporting systems. The relevance of the PBRR for the measurement reporting activity is clearly supported by the current findings. This study also shows that there is a general trend towards increased reporting activity. This is maintained by regional centres and encouragement of reporting. A further study would be helpful to assess the effectiveness of reporting systems at both the national and European level.

• MeSH
• databáze faktografické MeSH
• farmakovigilance MeSH
• sběr dat MeSH
• systémy pro sběr zpráv o nežádoucích účincích léků organizace a řízení   statistika a číselné údaje   trendy   MeSH
• zapojení pacienta metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

INTRODUCTION: Collecting information about drugs in clinical practice is essential for ongoing riskbenefit analysis of the drug use. Medical literature is an important source of new information on drug safety, in particular for the signal assessment. A signal is an information about a new potentially causal association, or a new aspect of a known association (e.g. change in frequency or severity of the reaction) between a drug and an adverse event (AE). AIM OF THE STUDY: To verify the effectiveness of the identification of adverse drug reaction (ADR) reports published in the local medical literature using MEDLINE and Embase, versus manual full text review of journals. MATERIAL AND METHODS: The study was performed for 20 randomly selected drugs and 84 Polish medical journals and covers a review of 1,576 individual journal issues with 20,146 articles. Retrospective analysis of literature reports collected during manual full text review was performed and compared to the outcome of database search. RESULTS: ADRs for analyzed drugs were identified only in 17 out of 84 journals, as a result of which 66 reports were analyzed. The majority of reports (55%) were found in local non-indexed journals. Three reports originated from journals indexed in MEDLINE and 9 reports from journals indexed in Embase were not found in these databases because databases do not fully cover conference abstracts and journal supplements. Moreover, while using databases for ADR report search there is a risk of missing up to 30% of ADR reports. The average gap between article publication date and database entry was 119 days. CONCLUSIONS: We verified that the effectiveness of the identification of ADR reports published in the local medical literature is more accurate based on manual full text review than by searching in bibliographic databases.

• MeSH
• lidé MeSH
• MEDLINE MeSH
• nežádoucí účinky léčiv * MeSH
• periodika jako téma * MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Polsko MeSH

BACKGROUND: The core motive of pharmacovigilance is the detection and prevention of adverse drug reactions (ADRs), to improve the risk-benefit balance of the drug. However, the causality assessment of ADRs remains a major challenge among clinicians, and none of the available tools of causality assessment used for assessing ADRs have been universally accepted. OBJECTIVE: To provide an up-to-date overview of the different causality assessment tools. METHODS: We conducted electronic searches in MEDLINE, EMBASE, and the Cochrane database. The eligibility of each tool was screened by three reviewers. Each eligible tool was then scrutinized for its domains (the reported specific set of questions/areas used for calculating the likelihood of cause-and-effect relation of an ADR) to discover the most comprehensive tool. Finally, we subjectively assessed the tool's ease-of-use in a Canadian, Indian, Hungarian, and Brazilian clinical context. RESULTS: Twenty-one eligible causality assessment tools were retrieved. Naranjo's tool and De Boer's tool appeared the most comprehensive among all the tools, covering 10 domains each. Regarding "ease-of-use" in a clinical setting, we judged that many tools were hard to implement in a clinical context because of their complexity and/or lengthiness. Naranjo's tool, Jones's tool, Danan and Benichou's tool, and Hsu and Stoll's tool appeared to be the easiest to implement into various clinical contexts. CONCLUSION: Among the many tools identified, 1981 Naranjo's scale remains the most comprehensive and easy to use for performing causality assessment of ADRs. Upcoming analysis should compare the performance of each ADR tool in clinical settings.

• MeSH
• farmakovigilance * MeSH
• hodnocení rizik MeSH
• lidé MeSH
• nežádoucí účinky léčiv * diagnóza   epidemiologie   prevence a kontrola   MeSH
• pravděpodobnost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Geografické názvy
• Kanada MeSH

OBJECTIVES: Ciprofloxacin induces rare neuro-psychiatric adverse drug reactions (ADRs) that are, as yet, not possible to predict due to unknown predisposition factors. BACKGROUND: The aim of the analysis was to assess the frequency of neuro-psychiatric ADRs and to identify potential risk factors that predisposed patients to ciprofloxacin neurotoxicity. METHODS: This observational retrospective study involved the evaluation of the medical records of patients in the Nephrology department and 3rd Internal Clinic of the General University Hospital in Prague. RESULTS: The overall incidence of neurological ADRs was 3.6 %. No neurological ADRs developed in patients aged less than 70 years. The covariates that were significantly more prevalent in the patients who developed neuropsychiatric ADRs were as follows: higher age, a history of neuropsychiatric disorders and the use of anticonvulsants. The administration of drugs from other ATC groups, gender, weight, body mass index, body surface area, renal functions, level of C-reactive protein at the beginning of treatment and the total daily dose/kg did not differ significantly between the two groups. CONCLUSION: Ciprofloxacin neuropsychiatric ADRs are more frequent in older patients with a history of neurologic or psychiatric disorders. No other tested covariates were proven to predispose patients to neuropsychiatric ADRs during treatment with ciprofloxacin (Tab. 2, Ref. 20).

INTRODUCTION: Herbal medicines are used worldwide and with an increasing popularity in Western countries. Although often perceived as 'naturally safe', herbals may cause severe adverse drug reactions (ADRs), with immediate allergic reactions being particularly life threatening. OBJECTIVES: The aim of this study was to analyse immediate allergy-like ADRs to herbals documented in VigiBase®, the WHO international pharmacovigilance database. METHODS: The documentation of all suspected ADRs in association with herbal exposure reported to VigiBase® from 1969 to August 2014 was retrieved. Among all reports in which WHO-ART reaction terms were indicative of acute allergic reactions, those classified as 'suspect' with a documented causality assessment and latency time of ≤1 day were selected. For the most frequent specific herbal-ADR combinations, the information component (IC) as a measure of disproportionality based on Bayesian statistics was calculated. RESULTS: We identified 757 reports out of 1039 ADRs. Products with mixed herbals (36.0 %) as well as those administered orally (63.2 %) were predominant. The most frequent reactions were urticaria and rash (49.2 %). Anaphylactic reactions accounted for 9.5 %. Disproportionally frequent reporting of mouth edema (IC = 1.81) and anaphylactic reactions (IC = 1.24) to Phleum pretense were noted. CONCLUSION: Our findings indicate that herbal medicines for oral use carry a risk of causing immediate allergy-like ADRs. Studies using the Vigibase® database can identify specific combinations of particular herbs and adverse reactions. Healthcare professionals and patients should be aware of these risks and report any serious adverse experiences.

• MeSH
• alergie etiologie   MeSH
• anafylaxe chemicky indukované   MeSH
• databáze faktografické MeSH
• dospělí MeSH
• farmakovigilance MeSH
• herbální medicína statistika a číselné údaje   MeSH
• léčivé rostliny škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nežádoucí účinky léčiv etiologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• systémy pro sběr zpráv o nežádoucích účincích léků statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: The purpose of this narrative review is to provide a comparison of several countries with different legislation and approaches to pharmacovigilance and to point out how these impact the number of adverse drug reactions (ADRs) that are reported to national competent authorities. METHODS: Legislative and statistical data regarding ADR reporting from various national competent authorities' websites, databases, and pharmacovigilance centers were used. In combination with the WHO pharmacovigilance quantitative indicator that was applied to evaluate the effectiveness of particular national pharmacovigilance systems in our scope. RESULTS: The study compared pharmacovigilance systems in six countries, focusing on ADR reporting from 2010 onwards. All countries required MAHs to report ADRs, while healthcare professionals' obligations varied. Per-capita ADR reports increased in all countries with available data, with the United States having a significantly higher reporting rate, possibly due to FDA campaigns. Despite starting later, China's per-capita reporting rate surpassed that of the Czech Republic and Japan. The study highlighted various measures taken by countries to enhance ADR reporting systems since the inception of their programs, contributing to the overall increase in reporting rates. CONCLUSIONS: ADR reporting is a global priority, with efforts made by different countries to strengthen their pharmacovigilance systems. Some success can be seen in gradually improving per-capita ADR reporting rates. The varying reporting rates and measures taken by each country may serve as a basis for further research and exchange of best practices to improve drug safety monitoring worldwide.

• MeSH
• databáze faktografické MeSH
• farmakovigilance * MeSH
• lidé MeSH
• nežádoucí účinky léčiv * epidemiologie   MeSH
• systémy pro sběr zpráv o nežádoucích účincích léků MeSH
• zdravotnický personál MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The use of herbal medicines in children and the general population is continually on the rise with an overall herbal lifetime and current use ranging between 0.8%-85.5% and 2.2%-8.9%, respectively. Although acute hypersensitivity reactions are generally considered to be rare, little knowledge exists on the frequency and type of these reactions especially in specific populations like children. OBJECTIVES: To assess the patterns of acute hypersensitivity reactions to herbal medicines reported to the WHO global individual case safety report (ICSR) database VigiBase® in children. STUDY DESIGN: From the original VigiBase® extract for the time between 1968 and 2014, we included all reports with adverse drug reactions (ADR) associated with herbal medicines in children where WHO-ART reaction terms were indicative of acute hypersensitivity reactions. RESULTS: VigiBase® contained 2646 ICSRs with 14 860 distinct adverse reactions reported in association with herbal medicine in children. Among those, 79 cases with 107 allergy-like reactions met our inclusion criteria. The most commonly reported WHO-ART terms were urticaria or rash/rash erythematous (59.8%), and allergic reaction (8.4%). The most frequently reported suspected herbal medicines were mixed herbal products (51.4%), Hedera helix (15.0%), and Echinacea purpurea (5.6%). Most frequent routes of administration were oral (75.9%), topical (8.9%), and rectal (3.8%). Over 30% of cases were reported in the age group from 7 to 12 years. The majority of reports were received from Germany (29.1%), Thailand (21.5%), and Australia (11.4%). CONCLUSION: VigiBase® contains a considerable number of acute hypersensitivity reactions in children associated with herbal medicines, including life-threatening reactions such as anaphylactic shock.

• MeSH
• databáze faktografické MeSH
• dítě MeSH
• herbální medicína statistika a číselné údaje   MeSH
• kojenec MeSH
• léková alergie epidemiologie   MeSH
• lidé MeSH
• mladiství MeSH
• nežádoucí účinky léčiv epidemiologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The aim was to study the impact of therapeutic drug monitoring (TDM) on paediatric patients on lamotrigine therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations. During the period of 2001-2015, 1308 pre-dose samples were taken from 430 patients <15 years of age as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Valproic acid decreased lamotrigine clearance by 54% in bitherapy, and by 21% in triple therapy with carbamazepine. Carbamazepine increased lamotrigine clearance by 191% in bitherapy. Levetiracetam and topiramate had no effect. The upper limit of lamotrigine therapeutic range (TR) was exceeded in 2% of cases in monotherapy, and in 6%-7% of cases in bi- or triple therapy. About 61% of plasma levels were found within the TR during 2001-2005, compared to 75% and 74% during 2006-2010 and 2011-2015, respectively. Adverse drug reactions (ADRs) were reported in 22 cases. Higher number of supratherapeutic levels in combination therapy led to a 3-fold increase in incidence of ADRs. Seizures occurred more often daily and monthly during 2001-2005 and in patients with three or four antiepileptic drugs in combination. Carbamazepine only partially compensated for the inhibitory effect of valproic acid. Lamotrigine clearance in monotherapy in children is similar to adults, but in polytherapy was found higher susceptibility to induction. A significantly higher number of supratherapeutic lamotrigine levels were found in combinations with valproate. Despite poor correlation with TR, both seizure frequency and ADRs declined after the implementation of TDM.

• MeSH
• antikonvulziva aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• dítě MeSH
• epilepsie krev   diagnóza   farmakoterapie   MeSH
• incidence MeSH
• karbamazepin aplikace a dávkování   škodlivé účinky   MeSH
• kombinovaná farmakoterapie škodlivé účinky   metody   MeSH
• kyselina valproová aplikace a dávkování   škodlivé účinky   MeSH
• lamotrigin aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• lékové interakce MeSH
• levetiracetam aplikace a dávkování   škodlivé účinky   MeSH
• lidé MeSH
• metabolická clearance MeSH
• mladiství MeSH
• monitorování léčiv * MeSH
• nežádoucí účinky léčiv epidemiologie   etiologie   prevence a kontrola   MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• topiramat aplikace a dávkování   škodlivé účinky   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH