| Abstract | CILJ ISTRAŽIVANJA
Cilj ovog specijalističkog rada je analizirati učestalost i karakteristike prijavljenih nuspojava antitrombotika (skupina B01 ATK klasifikacije lijekova) te ih usporediti s nuspojavama ostalih lijekova s osvrtom na mogući utjecaj interakcija kao rizičnog faktora za nastanak nuspojava antitrombotika. Poseban je osvrt dan na nove oralne antikoagulanse (NOAK) obzirom da su klinička ispitivanja i iskustvo nakon stavljanja u promet pokazali da pojava velikog krvarenja, uključujući i događaje koji su doveli do smrti, nisu ograničeni samo na antagoniste vitamina K i heparine niske molekularne težine, nego predstavljaju značajne rizike i kod novih oralnih antikoagulansa.
MATERIJALI I METODE
Provedena je retrospektivna opservacijska studija nuspojava antitrombotika (ATK: B01) prijavljenih HALMED-u, u razdoblju od 1. siječnja 2014. do 31. prosinca 2015. Podaci su analizirani obzirom na dob i spol bolesnika, vrstu, ozbiljnost, očekivanost, ishod, pripadnost organskom sustava nuspojave te prijavitelju, s osvrtom na učestalost nuspojava antitrombotika u ukupnom broju prijavljenih nuspojava.
Uočene potencijalne i aktualne interakcije u primjeni antitrombotika analizirane su koristeći interakcijske programe (Micromedex i Stockley) te su opisani slučajevi nastali kao posljedica najčešćih aktualnih interakcija.
Podaci su obrađeni deskriptivnom statistikom.
REZULTATI
U razdoblju od 1. siječnja 2014. do 31. prosinca 2015. zaprimljeno je 286 prijava sumnji na nuspojava lijekova iz skupine B01. Najveći broj prijava zaprimljen je za lijekove iz skupine antagonista vitamina K (34,5%) i njihovog najpoznatijeg predstavnika varfarina. Udio nuspojava antitrombotika koje ispunjavaju bar jedan od kriterija ozbiljnosti iznosio je 50,9% (145/286) u odnosu na sve prijave na nuspojave antitrombotika. Raspodjela ozbiljnih i ne-ozbiljnih nuspojava približno je slična i za lijekove iz skupine novih oralnih antikoagulansa (NOAK) u navedenom razdoblju gdje je od ukupnog broja prijavljenih nuspojava za lijekove iz ove skupine 48,2% (41/85) nuspojava označeno kao ozbiljne dok je 51,8 % (44/85) označeno kao ne-ozbiljne. S fatalnim ishodom zabilježeno je 68 nuspojava koje su prikupljene iz 17 prijava sumnji na nuspojave. Od 286 zaprimljenih prijava sumnji na nuspojave antitrombotika, 69,6% (199/286) prijava uključivalo je u terapiji više od jednog lijeka, 44,5% (127/286) prijava tri ili više lijekova u terapiji te čak 21% (60/286) prijava s više od šest lijekova u terapiji. U prijavama nuspojava antitrombotika identificirano je 61,8% (123/199) prijava s potencijalnim interakcijama antitrombotika od kojih je 30 prijava ocijenjeno da su nastale kao posljedica aktualne interakcije lijekova, odnosno 15,1% (30/199) slučajeva u kojem je pacijent uzimao više od jednog lijeka bilo je uzrokovano interakcijama. Od 30 prijava ocijenjenih da su nastale kao posljedica aktualne interakcije lijekova, 17 ih je bilo ozbiljnih nuspojava (56,6%).
ZAKLJUČAK
Udio ozbiljnih nuspojava antitrombotika znatno je veći od udjela ozbiljnih nuspojava prijavljenih za sve lijekove. Najviše nuspojava antitrombotika zabilježeno je za varfarin za kojeg je ujedno identificirano i najviše aktualnih interakcija. Nuspojave uzrokovane aktualnim interakcijama antitrombotika ozbiljnije su u usporedbi s nuspojavama ostalih lijekova te često zahtijevaju hospitalizaciju. Obzirom na ozbiljnost nuspojava ove skupine lijekova, potreban je povećani oprez pri njihovoj primjeni te edukacija zdravstvenih radnika i pacijenata. |
| Abstract (english) | OBJECTIVES
The objective of this paper is to analyse frequency and characteristics of reported adverse drug reactions (ADRs) of antithrombotic agents (B01 subgroup of ATC classification system) and to compare them with adverse drug reactions (ADRs) of other drugs as well as to assess drug-drug interactions as the risk factor and possible cause of antithrombotic agents' ADRs. Particular consideration is given to novel oral anticoagulants (NOAC) since clinical trials and clinical experience following the marketing of these drugs have shown that major bleeding and adverse drug events are not limited only to vitamin K antagonists and low molecular weight heparins but also pose a significant risk with the use of novel oral anticoagulants (NOAC).
MATERIAL AND METHODS
A retrospective observational study of antithrombotic agents' (ATC B01) adverse drug reactions (ADRs) reported to HALMED in the period of January 1, 2014 to December 31, 2015 was performed. The data were analysed with regard to age and gender of a patient, type, seriousness, expectedness, outcome, distribution to system organ class (SOC) and reporter of the ADRs including the assessment of the antithrombotic agents' ADRs in reference to the total number of the reported ADRs.
Observed potential and actual drug-drug interactions of antithrombotic agents were analysed using drug interaction programs (Micromedex and Stockley) and cases caused by most frequent actual drug-drug interactions were described.
Data were analysed using descriptive statistics.
RESULTS
In the period from January 1, 2014 to December 31, 2015, a total of 286 reports of adverse drug reactions (ADRs) were received for drugs with B01 ATC code. The highest number of the reports was received for drugs belonging to the subgroup of vitamin K antagonists (34.5%) and its most known representative warfarin. Percentage of antithrombotic agents’ ADRs fulfilling at least one of the criteria of seriousness was 50.9% (145/286) in relation to the total number of all ADRs reported for antithrombotic agents. Distribution of serious and non-serious ADRs was similar for novel oral anticoagulants (NOAC) for the observed time period and out of total number of reported ADRs for NOACs, 48.2% (41/85) was identified as serious and 51.8 % (44/85) as non-serious. 68 ADRs collected from 17 ADR’s reports were identified with fatal outcome. Out of 286 ADR reports for antithrombotic agents, 69.6% (199/286) involved more than one drug, 44.5% (127/286) reports involved three or more drugs and almost 21% (60/286) reports involved more than six drugs in the therapy. In the ADRs reports for antithrombotic agents, 61,9% (123/199) reports were identified with potential drug-drug interactions caused by antithrombotic agents and out of which 30 reports were assessed as caused by actual drug-drug interaction, that is, 15.1% (30/199) cases in which patient used more than one drug were caused by drug-drug interactions. 17 reports out of 30 reports assessed as caused by actual dug-drug interaction were serious ADRs (56.6%).
CONCLUSION
The percentage of antithrombotic agents' serious ADRs is significantly higher than the percentage of serious adverse reactions reported for all drugs. The highest number of antithrombotic agents' ADRs and actual drug-drug interactions were identified for warfarin. ADRs caused by actual drug interaction of antithrombotic agents were more serious in comparison with ADRs caused by other drugs and had required frequent hospitalisations. Considering the seriousness of ADRs caused by this group of drugs, an increased vigilance is needed with the use of these drugs as well as education of healthcare professionals and patients. |
