Farmalološke karakteristike direktnih oralnih antikoagulansa i njihovih antidota

master's thesis

• Title (english): Pharmacological characteristics of direct oral anticoagulants and their antidotes
• Author: Mirna Puhar
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Jasna Jablan (član povjerenstva)
• Committee member: Maja Bival Štefan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2021-07-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

U posljednjih desetak godina nekoliko je oralnih antikoagulansa odobreno za upotrebu u indikacijama
povezanim s profilaksom i liječenjem venske i arterijske tromboembolije. Direktni oralni
antikoagulansi (DOAK) ili novi oralni antikoagulansi su lijekovi koji svoj antikoagulacijski učinak
ostvaruju izravnom inhibicijom trombina (dabigatran) ili izravnom inhibicijom faktora Xa
(rivaroksaban, apiksaban, edoksaban i betriksaban). Antagonisti vitamina K (VKA) dugo su bili
antikoagulansi prvog izbora, ali DOAK imaju mnogo prednosti u odnosu na VKA, poput
jednostavnijeg doziranja, brzog nastupa i prekida djelovanja, predvidljivog odgovora na dozu,
stupanja u manje interakcija s drugim lijekovima, a nije potrebno niti laboratorijsko praćenje. S druge
strane, kontraindicirani su kod pacijenata s teškim oštećenjem bubrega i imaju višu cijenu od
varfarina. U ovom radu opisuju se farmakološka svojstva DOAK-a, njihova djelotvornost, sigurnost
i podaci iz ključnih studija koji podržavaju trenutno odobrene indikacije. Farmakokinetičke
karakteristike dostupnih DOAK-a (dabigatran, rivaroksaban, apiksaban, edoksaban, betriksaban)
bitno se razlikuju u pogledu oralne bioraspoloživosti, vezanja na proteine plazme, načina i stupnja
biotransformacije, kao i načina eliminacije. Posljednjih godina na tržištu su dostupni i specifični
antidoti: andeksanet-alfa za rivaroksaban i apiksaban te idarucizumab za dabigatran. Mogućnost
zaustavljanja djelovanja antikoagulansa kada je to nužno, dodatno je utjecala na veću sigurnost
propisivanja i primjene ovih lijekova.

Abstract (english)

In the last ten years, several oral anticoagulant drugs have become available for use in indications
related to prophylaxis and treatment of venous and arterial thromboembolism. Direct oral anticoagulant
drugs (DOACs) or new oral anticoagulant drugs are medicines that achieve their anticoagulant effect
by the direct inhibition of thrombin (dabigatran) or by the direct inhibition of factor Xa (rivaroxaban,
apixaban, edoxaban and betrixaban). Vitamin K antagonists have been anticoagulants of the first choice
for a long time, but DOACs have many advantages in related to VKA, such as simpler dosage, rapid
onset and interruption of action, a predictable dose response, few drug–drug interactions and no
laboratory monitoring is required. However, they are contraindicated in patients with severe renal
impairment and their price is several times higher than warfarin. In this dissertation, the
pharmacological characteristics of DOACs, their efficacy, safety and data from pivotal studies that
support currently approved indications are described. The pharmacokinetic characteristics of available
DOACs (dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban) differ substantially as regards oral
bioavailability, plasma protein binding, type and phase of biotransformation and way of elimination.
In recent years, specific antidotes: andexanet-alpha for rivaroxaban and apixaban and idarucizumab for
dabigatran are available. The ability to stop the action of anticoagulants, when necessary, further affects
the greater safety of prescribing and administration of these drugs.

• Keywords: direktni inhibitori trombina; inhibitori faktora Xa; antidoti; faktor Xa; tromboprofilaksa; antikoagulans
• Keywords (english): direct thrombin inhibitors; factor Xa inhibitors; antidotes; factor Xa; thromboprophylaxis; anticoagulant
• Language: croatian
• URN:NBN: urn:nbn:hr:163:210360
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-04-27 11:39:26