Search

Uvod Medikacijske pogreške su nenamjerne greške u propisivanju, čuvanju, izdavanju, pripremi i primjeni lijekova u kliničkoj praksi koje su uzrokovale ili su mogle uzrokovati nuspojave. Primjena lijekova u djece identificirana je kao rizični faktor za nastanak medikacijskih pogrešaka te se objašnjava složenim doziranjem u djece pri čemu je predoziranje najčešće prijavljena medikacijska pogreška u djece (procijenjeno je da predoziranje uzrokuje 21% svih medikacijskih pogrešaka u djece) [1-4]. Povremeno postoji potreba za složenim otapanjem od strane zdravstvenih radnika te su medikacijske pogreške povezane s infuzijama otopina i elektrolita česte. Tekuće formulacije koje se često koriste u djece mogu biti rizični faktor ako se koristi neprimjereno pomagalo za doziranje. Pokazano je kako su odmjerne šprice najprikladnije za točno doziranje tekućih formulacija u djece [5]. Cilj Analizirati uzroke medikacijskih pogrešaka spontano prijavljene Agenciji za lijekove i medicinske proizvode (HALMED) kako bi se upozorili zdravstveni radnici te smanjio nastanak nuspojava uzrovan medikacijskim pogreškama. Metode Baza nuspojava HALMED-a pretražena je koristeći standardnu pretragu Standardised MedDRA Query (SMQ) u regulatornom medicinskom rječniku Medical Dictionary for Regulatory Activities (MedDRA) te su identificirani slučajevi u kojima je prijavljena medikacijska pogreška u osoba mlađih od 18 godina, pristigli zaključno s 31.12.2021. Prijavljeni slučajevi medikacijskih pogreška analizirani su prema spolu i dobi pacijenta. Detaljno su analizirani slučajevi medikacijskih pogrešaka djelatnih tvari PS-6 Klinička farmacija u sustavu zdravstva: MOGUĆNOSTI I IZAZOVI 102 za koje je prijavljeno više od 10 slučajeva kako bi se utvrdili uzroci nastanka medikacijske pogreške. Najčešće medikacijske pogreške dodatno su analizirane prema vrsti medikacijske pogreške te ATK skupini djelatne tvari. Rezultati Baza nuspojava HALMED-a je na dan 31.12.2021. sadržavala 8 375 prijava za pacijente mlađe od 18 godina od kojih se 1 610 prijava odnosilo na slučajeve medikacijskih pogrešaka u djece. Medikacijske pogreške za najčešće djelatne tvari najviše su prijavljene u dobnoj skupini od 2 do 11 godina (67%) te za dječake (53%). Ukupno 912 (57%) slučajeva se odnosilo na djelatne za koje je prijavljeno više od 10 slučajeva medikacijskih pogrešaka u djece te su ti slučajevi detaljno analizirani kako bi se utvrdili uzroci medikacijskih pogrešaka. Najčešće prijavljene medikacijske pogreške bile su slučajna izloženost i predoziranje. Djelatne tvari koje su najčešće uzrokovale medikacijske pogreške pripadale su sljedećim ATK skupinama: lijekovi s učinkom na probavni sustav i mijenu tvari (ATK skupina A), lijekovi koji djeluju na krv i krvotvorne organe (ATK skupina B), lijekovi koji djeluju na kardiovaskularni sustav (ATK skupina C), lijekovi koji djeluju na kožu – dermatici (ATK skupina D), lijekovi koji djeluju na urogenitalni sustav i spolni hormoni (ATK skupina G), sustavni hormonski lijekovi, izuzev spolnih hormona (ATK skupina H), lijekovi za liječenje sustavnih infekcija (ATK skupina J), lijekovi koji djeluju na koštano-mišićni sustav (ATK skupina M), lijekovi koji djeluju na živčani sustav (ATK skupina N), lijekovi koji djeluju na respiratorni sustav (ATK skupina R). Prvih pet najčešće prijavljenih djelatnih tvari bile su: kolekalciferol, ibuprofen, salbutamol, paracetamol i diazepam. Najčešći uzroci koji su doveli do medikacijske pogreške bili ostavljanje lijeka izvan nadzora roditelja (diazepam, ketoprofen, acetilsalicilna kiselina, bisoprolol, alprazolam, etinilestradiol i gestoden, varfarin, klonazepam, zolpidem), privlačno pakiranje i primamljiv okus lijeka (Hedera helix sirup, ibuprofen, acetilsalicilna kiselina, paracetamol sirup), primjena krive doze lijeka od strane roditelje zbog nerazumijevanja uputa (salbutamol, dimetiden, trovalentno željezo, amoksicilin i klavulanska kiselina, amoksicilin, azitromicin, paracetamol), lijek iz uvoza (valproat), zamjena jačina lijekova za lijekove iste formulacije (ibuprofen sirup, zamjena čepića paracetamola), zamjena lijekova zbog sličnosti u izgledu i načinu doziranja (vitamin D i naftifin, vitamin D i simetikon, vitamin D i salbutamol, dimetiden i bromheksidin kapi), složeno razrjeđivanje - pogreške u doziranju uzrokovane zabunom između miligrama (mg) i mililitra (ml) (paracetamol primijenjen intravenozno), primjena neprikladne formulacije za djecu (valproat, pantoprazol) i korištenje krivog dozatora (oralna otopina trovalentnog željeza). 3. hrvatski kongresKLINIČKE FARMACIJE 09. - 11. lipnja 2022. Hilton Garden Inn, ZAGREB 103 Zaključak Ukupno 19% svih spontano prijavljenih slučajeva HALMED-u u pacijenata mlađih od 18 godina odnosilo se na medikacijske pogreške što upućuje na važnost poznavanja uzroka medikacijskih pogrešaka kako bi se iste mogle spriječiti. Potreban je poseban oprez u slučajevima kada postoje različite jačine lijeka iste formulacije, kada se istodobno primjenjuju slični lijekovi (slična formulacija i sličan način doziranja), kada se primjenjuje lijek iz uvoza koji nije opremljen na hrvatskom jeziku, kod primjena jako male količine lijeka i primjene lijekova koje zahtijevaju složeno razrjeđivanje. Jako je važno čuvati lijekove izvan dohvata djece jer je ovo najčešći uzrok medikacijskih pogrešaka u djece

Background/Introduction: New European (EU) pharmacovigilance (PV) legislation, introduced in 2012, widened the scope of an Adverse Drug Reactions definition so that it also includes noxious and unintended response to a medicinal product arising from the use outside the terms of the marketing authorisation (MA), whereby the use outside the MA also includes off-label use, overdose, misuse, abuse and medication errors (MEs). Objective/Aim: To describe ADRs arising from the use outside the terms of the MA reports in the Croatian pharmacovigilance database. Methods: A retrospective, observational study of the HALMED PV database. The outcome measure included ADRs arising from the use of the products outside the terms of the MA. An assessment was performed based on the information provided in a reference document, an SmPC, on a case-by-case basis, using predefined criteria. Results: Among 679 ADRs included in the analysis, 162 (23.9%) ADR reports were related to the use outside of the MA, 370 (54.5%) were related to the use within the MA and 147 (21.6%) were adjudged as not-assessable. Majority were due to medication errors (N = 155). Off-label use was identified in 87 reports, while misuse and overdose were identified in 11 and 39 reports, respectively. There were no reports of abuse among the analysed reports. In only 27 out of 128 reports (21.09%), reporters recognized an ADR as a consequence of use outside MA. Conclusion: The main observation derived from this study was a rather high proportion of ADR reports that arise from the medicinal product use outside the use of MA. Moreover, a considerable portion of ADRs outside the terms of the MA was not- assessable nor recognized by a reporter, suggesting the need for targeted education and improving reporting systems, since forms currently used were not designed for reporting ADRs outside the MA. Disclosure of Interest: None declared.

Uvod Povećanje pogrešne uporabe i zlouporabe lijekova globalni je javnozdravstveni problem. Značajan broj lijekova koji se nalaze ureceptnom i bezreceptnom imaju visok potencijal pogrešne uporabe i zlouporabe. Odgovornost je na ljekarnicima da prepoznaju ovaj problem te se aktivno uključe u njegovo suzbijanje kroz informirano savjetovanje pacijenata što uključuje uvid ljekarnika u sve izdane lijekove, prepoznavanje rizičnih faktora te prikladno upućivanje ove skupine bolesnika nadležnim liječnicima. Cilj Cilj ove radionice je na slučajevima bolesnika koji pogrešno primjenjuju i/ili zlorabe lijekove procijeniti terapiju, identificirati terapijske probleme i predložiti moguće ljekarničke intervencije. Dodatno, cilj je predložiti mjere koje bi ljekarnicima mogle omogućiti sprečavanje i rješavanje razvoja ovisnosti. Način izvođenja Radionice će se provesti u interaktivnom formatu učenja temeljenog na problemu (engl.rob-lem- basedlearning, PBL) gdje će polaznici u malim skupinama rješavati konkretne slučajeve iz prakse. Svi polaznici radionica dobit će predložena konačna rješenja po završetku radionica Ishodi učenja Po završetku radionice polaznici će se upoznati sa skupinama lijekova koji nose najveći potencijal za pogrešnu uporabu i zlouporabu te s ključnim mjerama čijom bi se implementacijom problem zlouporabe i pogrešne primjene lijekova mogao smanjiti. Dodatno, upoznat će se s protokolima ukidanja terapije nakon dugotrajnijeg liječenja benzodiazepinima i/ili z-lijekovima mjerama sprečavanja i rješavanja ovisnosti o kodeinu itd.

Uvod: Medikacijske pogreške smatraju se jednim od najčešćih uzroka nuspojava koje su se mogli spriječiti te predstavljaju jedan od vodećih javnozdravstvenih problema u svijetu. Svrha rada: Svrha ovog rada je utvrditi učestalost te ocijeniti i opisati medikacijske pogreške među spontano prijavljenim nuspojavama lijekova Agenciji za lijekove i medicinske proizvode (HALMED). Metode: Retrospektivno opservacijsko istraživanje provedeno je na uzorku od 300 spontano prijavljenih nuspojava u 2012. i 2016. godini. Prethodno validirana "P-metoda" [1] i smjernice Europske agencije za lijekove [2] korištene su za otkrivanje medikacijskih pogrešaka među prijavljenim nuspojavama HALMED-u. Rezultati: Svaka peta nuspojava bila je uzrokovana medikacijskom pogreškom. U većini slučajeva (99, 3%) medikacijska pogreška nije bila identificirana od strane prijavitelja već samo ocjenitelja. U slučajevima u kojima su medikacijske pogreške dovele do nuspojave, najveći broj suspektni lijekova pripadao je Ci N skupinama ATK klasifikacije lijekova. Najčešća identificirana medikacijska pogreška koja je dovela do nuspojave bila je "netočna doza" (29, 6% slučajeva). Zaključak: U velikom broju slučajeva medikacijska pogreška je dovela do razvoja nuspojava. Nuspojave najčešće nisu bile prepoznate od strane prijavitelja što ukazuje na potrebu za ciljanom edukacijom i izmjenama samog obrasca za prijavljivanje nuspojava.

Introduction As laid down in the Directive 2010/84/EU amending, Directive 2001/83/EC on the Community code, term 'adverse drug reaction' is noxious and unintended effects resulting not only from authorised use of a medicinal product at normal doses, but also from medication errors and uses outside the terms of the marketing authorisation, including overdose, abuse and misuse and suspected adverse reactions associated with occupational exposure. Medication errors are the most common preventable cause of adverse drug reactions (ADRs) in medication practice and present a major public health burden. Materials and methods Non-interventional, observational study aimed at identifying, evaluating and describing preventable adverse drug reactions among the spontaneously reported ADRs was conducted. The previously validated “P-method” was employed as to systematically detect preventable ADRs among the individual case safety reports (ICSR) reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED). Additionally, medication errors were analyzed according to the „Good practice guide on recording, coding, reporting and assessment of medication errors”1. Results A high proportion of MEs was identified among the spontaneously reported ADRs to the HALMED. In most cases ME was identified only by an assessor and not recognized by a reporter. The two most commonly identified preventability criteria for ADR occurrence were “Incorrect dose” and “Documented hypersensitivity to administered drug”. On the other hand, among MEs without harm “Labelled drug-drug interaction” was the most commonly identified type of ME. Conclusion Our results indicate the need for enforcing a standardized education for reporters and for customizing ADR forms for ME reporting.

Background: Medication errors are the most common preventable cause of adverse drug reactions (ADRs) in medication practice and present a major public health burden. Aim of the study: The objective of the study was to identify, evaluate and describe medication errors (ME) among the spontaneously reported ADRs to the Croatian Agency for Medicinal Products and Medical Devices (HALMED). Method: A retrospective observational study was performed on 100 spontaneously reported ADRs in 2013. The previously validated ‘‘P-method’’1 was employed to systematically detect MEs in individual case safety reports (ICSR) sent to the Croatian pharmacovigilance centre (PVC) at HALMED. ME that lead to ADR identified by reporter as well as ME suspected by assessor are described. Results: Ninety-seven MEs were detected in 100 analysed cases [gender 38 M, 62 F ; age 56.1 ± 21.9 (range 2–93) ; number of medicines 2.8 ± 2, 0 (range 1–13), comorbidities 1.7 ± 1.2 (range 0–5)]: 21, 65 % (n=21) related to a suspected drug led to an ADR, whereas 78, 3 %(n=76) related to both suspected drug or concomitant therapy did not lead to harm. In only 3 cases (14, 29 %) ME that lead to ADR was identified by reporter. Out of 36 (36 %) spontaneously reported serious ADRs, 9 (25 %) were caused by medication errors. The most commonly identified preventability criteria for ADR occurrence was ‘‘Drug–drug interaction’’ reported in 24.7 % of overall MEs, followed by ‘‘Incorrect dose’’ (21.6 %). Conclusion: A high proportion of MEs was identified in ICSRs sent to PVC with one fourth of the serious ADRs caused by medication errors. In 20 % of reported ADRs MEs was identified. In most cases (86 %), ME was suspected only by assessor. In process of identifying a medication error in practice it is very hard to check that in particular case it was unintended failure in the drug treatment process. Process of identifying ME is very sensitive and relationship between reporter and national pharmacovigilance centre as well as legal implications in the context of HCP liability in some countries must be taken into account. Our results indicate the need to capture suspected ME by assessor in databases as well as promoting reporting of ME and customizing ADR forms for reporting ME.

Rationale and background For the marketed COVID-19 vaccines, a pan-European cohort event monitoring system is an important addition to existing spontaneous reporting systems for signal detection. This enables the collection of patient-reported safety data in near real-time and generates incidence rates of vaccine-related adverse reactions. Research question and objectives Primary aim To collect data on patient-reported adverse reactions of different COVID-19 vaccines, estimate the frequency, compare incidence rates across the participating countries in general and special populations (pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy, and people with prior SARS-CoV-2 infection) in near-real-time. Secondary aim To identify and generate incidence rates and potential predictors of the most frequently reported adverse reactions related to different COVID-19 vaccines after first/second dose(s) of the first vaccination cycle as well as booster doses within the general population and special cohorts of vaccinees. Study design Prospective cohort study in general and special populations (pregnant and lactating women, children and adolescents, immunocompromised, people with history of allergy and people with prior SARS- CoV-2 infection). Data are prospectively collected, directly from vaccine recipients in 11 countries. The common core data from different countries were pooled, stratified by special cohort and analysed at the European level. The study is set up as a cohort monitoring for a duration of up until 6 months from the first dose vaccination date (except for pregnant women who are followed up until 1.5 month after the pregnancy end). Data were collected using the Lareb Intensive Monitoring (LIM) system (general population first dose), the Research Online (RO) tool (booster and special populations), the Croat OpeN data collection system and the German SafeVac2.0 data collection system. Setting Participants to be included should be vaccinated in one of the participating countries in the period ranging from December 2020 (in Countries already starting prospective monitoring in ECVM) until August 2022. This interim report includes LIM and RO data updated until the 9th of February 2022, and Croat OPeN data until the 15th of February 2022. German SafeVac 2.0 datasets are included in batches, with Moderna data updated until May 2021, AstraZeneca until September 2021, and the new BioNTech/Pfizer data until March 2022. Subjects and study size General and special population vaccinees (pregnant and lactating women, children, adolescents, immunocompromised, people with a history of allergy, and people with prior SARS-CoV-2 infection) who were recruited at multiple vaccination centers within 48 hours from either the first or booster COVID-19 vaccine dose administration. The aim was the inclusion of up to 60,000 vaccine recipients belonging to both general and special cohorts from 12 European countries which would exceed the numbers of vaccinated in clinical trials. Variables Vaccine brand and batch number, adverse drug reactions (ADRs), age, sex, height and weight, geographical area, medical history including information on comorbidities and concomitant diseases, and concomitant medications. Results The populations that adhere to this observational study are described in this report by the number of patients included in the cohort for each participating country, gender distribution, age categories, and vaccine brands. First vaccination cycle data in general population For both general and special populations, dedicated cumulative structured overviews of numbers and incidences of all adverse reactions are provided. Reported adverse events are stratified in solicited, unsolicited, serious adverse events, adverse events of special interest, vaccine brand, country, gender, and age groups when all these informative details can be extrapolated from the data. For the first vaccination cycle, in this report we included 30,108 participants in Belgium, Croatia, France, Italy, the Netherlands, and the United Kingdom, and 520,076 general population participants from Germany. Across the sites 0.2-0.3% % reported at least one serious adverse reaction after receiving the first and/or the second dose. The majority of all reports of an AESI were from females, across all vaccine brands. Special populations first vaccination Among the 7,057 vaccinees in the special populations who reported at least one ADR following the first vaccination dose, 17 (0.2%) reported at least one serious ADR. In 3,793 vaccinees who reported at least one ADR following the second vaccination dose, 9 (0.2%) reported at least one serious ADR. Out of the total number of vaccinees who reported at least one ADR following the first (N= 7,057) and second (N= 3,793) vaccination dose, 25 (0.4%) and 15 (0.4%) vaccinees reported at least one AESI following the first and second vaccination dose, respectively. The most reported solicited local adverse reaction among all the COVID-19 vaccine brands, special cohorts, and between 1st and 2nd dose is injection site pain. This is in line with the general population observations (and with previously published works). Among the solicited systemic adverse reactions, fatigue, headache, malaise, and myalgia, were the most frequently reported events, which is consistent with total populations. Serious adverse reactions and AESI were uncommon among each of the special cohorts, although sample size and power to detect differs. This is also in line with the general populations' pivotal clinical trials and this study's results in general populations. Caution should be taken in interpreting the data as analysis considering participants’ baseline characteristics and the adverse reaction they reported has not yet been conducted. On the basis of the Research Online app that was used in Italy, Romania, Slovakia, Spain and Switzerland, 377 first dose vaccinees with one of the special conditions were included mostly children and persons with prior Sars-Cov-2 infection. The rate of serious reactions could not yet be validly estimated. Pregnant women: 8 cases of spontaneous abortion events were observed among both general and special population data, but only 1 case was recorded as pregnant women at baseline. No other AESI were yet observed. Children/adolescents: Serious ADRs following COVID-19 vaccination are uncommon. No AESI were observed. Immunocompromised, people with history of allergy, people with prior COVID-19: Serious ADRs and AESI after COVID-19 vaccinations are uncommon. Among the observed AESI, COVID-19 infection, hypersensitivity, and arrhythmia, have been the most frequently reported. Booster dose A total of 11.100 subjects who received a booster dose were included in this study, all use the RO application for enrolment. Most of the persons were not part of a special population (8493), 419 pregnant or lactating women were included. BioNTech/Pfizer and Moderna are the most commonly administered COVID-19 vaccines in our observational study. Children/adolescents reported the lowest rate of ADRs among the cohorts involved in this booster vaccination study. Lactating women reported the highest numbers of ADRs. Informative details about the type of the reported ADRs are not yet reported for these booster dose data. Conclusion This interim report summarises the safety evidence of covid-19 vaccines in more than 550,000 persons from both the general and special populations that were included after first dose, and booster doses. We combined data originating from a total of eleven countries and four different data capture systems. Solicited reactions were comparable to those observed in trials. Across the sites 0.2-0.3% % reported at least one serious adverse reaction after receiving the first and/or the second dose, this was similar after the first booster., The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network (led by Utrecht University) with collaboration from the Vaccine Monitoring Collaboration for Europe network (VAC4EU). The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/23/PE. This report expresses the opinion of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties. The work in this report is based on: EU PAS Register No: WP1: EUPAS42504 WP2: EUPAS39798