Akademik Veri Yönetim Sistemi
18. World Congress of Basic and Clinical Pharmacology, Kyoto International Conference Center Kyoto – Japonya, Tokyo, Japonya, 1 - 06 Temmuz 2018, cilt.31213
Assessment Of Dabigatran, Rivaroxaban And Apixaban
With Respect To Drug-Drug Interaction In A University Hospital
Objective: Vitamin K antagonists are used in the
treatment and prevention of thrombosis. New oral anticoagulants (NOAC) have
been developed in recent years. These include the thrombin inhibitor
dabigatran, the factor Xa inhibitors rivaroxaban and apixaban. We aimed to
evaluate potential drug-drug interactions (PDDI) that could be presented by
pharmacokinetic (PK) and pharmacodynamic (PD) pathways of NOACs, which are
prescribed in a university hospital.
Methods: All prescriptions of patients who were
prescribed NOAC in Gazi University Medical Faculty Hospital between 1 November
2012 and 30 November 2017 were reviewed retrospectively for PK and PD PDDI for
6 months from the date of NOAC prescription. Hospital Information Management
System data were used. PDDI assessment was based on prescribing information of
drugs, PK and PD interaction mechanisms and literature information.
Prescription with P-glycoprotein and CYP3A4 inducers and inhibitors has been
considered as PK interaction. Prescription with other medications that may
increase the risk of bleeding has been considered as PD interaction.
Descriptive and percentage statistical evaluations were performed.
Results: 2023 patients (mean age 70.3 ± 13.1 years)
who received NOAC treatment were included. Among these patients, 552 used
dabigatran, 1107 used rivaroxaban and 364 used apixaban. 1031 of 11139
prescriptions written to 2023 patients contained PDDI in terms of PK and/or PD.
These 1031 prescriptions included 554 patients (27.4% of all patients). Of
these patients, 77.1% were 65 years of age or older. Among the prescriptions
containing PDDI (1031 prescriptions), 37.5% had a risk of PK interaction and
67.2% had a risk of PD interaction. The percentage of prescriptions written for
drugs with potential for both PK and PD interaction was 2.4%. In 3.4% of
prescriptions containing PDDI, the drugs defined as contraindicated according
to the prescribing information of NOACs were written. Rifampin was the most
frequent prescribed drug (51.4%) among these drugs.
Conclusions: A significant proportion of the prescriptions of patients who use NOAC contains PDDI (9.26%). The majority of PDDI was PD. These drugs may be prescribed together to enhance therapeutic effect. However, the high percentage of PDDI in which selective serotonin reuptake inhibitors / serotonin noradrenaline reuptake inhibitors are found suggests that there are no safer alternatives. In terms of PK, it would be beneficial to recommend monitoring during their use with P-glycoprotein and/or CYP3A4 inhibitors.
Keywords: new oral anticoagulants; drug-drug interaction