Prescribers' compliance with summary of product characteristics of dabigatran, rivaroxaban and apixaban—A European comparative drug utilization study

Abstract

Despite a tremendous increase of direct oral anticoagulants (DOACs) prescriptions in recent years, only few data is available analysing prescribers' adherence to Summary of Product Characteristics (SmPC). We aimed to assess adherence to registered indications, contraindications, special warnings/precautions, and potential drug‐drug interactions for three DOAC compounds (dabigatran, rivaroxaban, and apixaban) in six databases of five European countries (The Netherlands, United Kingdom, Spain, Denmark, and Germany). We included adult patients (≥18 years) initiating DOACs between 2008 and 2015. For several SmPC items, broad definitions were used due to ambiguous SmPC terms or lacking data in some databases. Within the study period, a DOAC was initiated in 407 576 patients (rivaroxaban: 240 985 (59.1%), dabigatran: 95 303 (23.4%), and apixaban: 71 288 (17.5%)). In 2015, non‐valvular atrial fibrillation was the most common indication (>60% in most databases). For the whole study period, a substantial variation between the databases was found regarding the proportion of patients with at least one contraindication (inter‐database range [IDR]: 8.2%‐55.7%), with at least one special warning/precaution (IDR: 35.8%‐75.2%) and with at least one potential drug‐drug interaction (IDR: 22.4%‐54.1%). In 2015, the most frequent contraindication was “malignant neoplasm” (IDR: 0.7%‐21.3%) whereas the most frequent special warning/precaution was “prescribing to the elderly” (≥75 years; IDR: 25.0%‐66.4%). The most common single compound class interaction was “concomitant use of non‐steroidal anti‐inflammatory drugs” (IDR: 3.0%‐25.3%). Contraindications, special warnings/precautions, and potential drug‐drug interactions were present in a relevant number of new DOAC users. Due to broad definitions used for some SmPC terms, overall proportions for contraindications are prone to overestimation. However, for unambiguous SmPC terms documented in the databases sufficiently, the respective estimates can be considered valid. Differences between databases might be related to “true” differences in prescription behaviour, but could also be partially due to differences in database characteristics.

Oral anticoagulants and concurrent rifampin administration in tuberculosis patients with non-valvular atrial fibrillation

“…Previous studies mainly focused on the effect of major bleeding between NOACs and CYP3A4 and/or P-gp inhibitors [ 23 , 24 ]. Concurrent NOAC use with potent CYP3A4 and/or P-gp inducers was only listed as less than 1% of included patients in six European databases from five European countries [ 25 ]. Furthermore, they did not describe the impact between NOACs and potent CYP3A4 and/or P-gp inducers such as phenytoin, carbamazepine, and rifampin.…”

Adoption of new medicines in primary care: A comparison between the uptake of new oral anticoagulants and diabetes medicines

“…Because of the impact of guidelines on prescription behaviour, it is interesting to shed light on the prescription patterns in the period before and shortly after those medicines were recommended in the guidelines. Although former studies have focused on the uptake patterns of both new medicine classes, 16,17 uptake of the medicine classes in primary care has not been compared. In addition, it is not known whether early adoption of DOACs is associated with the early adoption of incretin‐based therapies and vice versa.…”