Discussion
There is a paucity of research on drug-drug interactions and prescriptions appropriateness among ESRD patients who have been prescribed QTcP-inducing drugs in Jordan. We adopted holistic and valid operational techniques to detect DDIs and evaluate the prescriptions appropriateness. Our findings can be confidently generalised, since the sample in our study was representative, with low margin of error, and randomly selected from all regions in Jordan. However, our study had limitations; this research was conducted in outpatient setting, and thus our data cannot reflect the prescribing behaviour in the inpatient settings. Due to insufficient resources and the limited nature of our data, patients with acquired r congenital QTc prolongation were not clinically identified. Nevertheless, we were tied by the study aims and the nature of the data, and our study can provide comprehensive assessment of prescribing behaviour in the outpatient clinics of Jordan.
In Jordan, Ahmad Al-Azayzih et al., (18), investigated the patterns of QTcP-inducing drugs usage among geriatric patients in North Jordan. DDIs and prescriptions appropriateness were not assessed, and ESRD patients were not screened. Furthermore, their findings cannot be generlised as they targeted patients in geographic area in Jordan. Many previous studies were conducted in the USA (37,38), Colombia (39), Germany (40), and India (41) assessed the patterns of QTcP-inducing drugs prescriptions. Despite that patients with ESRD are at high risk of developing fatal QTcP, none of the recent studies screened for DDIs or prescriptions appropriateness among this patient group particularly.
Among the included patients in our study, 954 QTcP-inducing drugs were prescribed; most of them were furosemide (36.2%) and lanzoprazole (28.9%). This was consistent with Ahmad Al-Azayzih et al., (18), where lanzoprazole (20.7%) and furosemide (15.8%) accounted for the most common prescribed QTcP-inducing drugs. Most of dispensed QTcP-inducing drugs in our study were categorised as conditional risk of QTcP. A recent study reported higher rate of mortality among patients who have been prescribed QTcP-inducing drugs with known or possible risk of QTcP than those who were on drugs with conditional risk or not on QTcP-inducing drugs at all (42). This finding focused on patients in psychiatry clinics, and thus cannot be generlised to other patient groups.
Our results suggested high rate of DDIs (64.8%) between QTcP inducing drugs and other medications; more than one-third of these DDIs were major and moderate. In addition, polypharmacy and co-morbidity were significantly related to this proportion. This result may attributed to low pharmaceutical care interventions, physicians poor adherence to the guidelines, and absence of clinical decision support system in the operated computerized physician order entry system (CPOE) . Our findings are in line with other studies in Jordan that indicated high rate of DDIs and poor adherence to the guidelines by physicians (21,22,27). The difference between the recent studies in Jordan and our study is that the patient group in our research is highly vulnerable to severe deadly complications, and thus urgent precautionary measures are necessary. In Saudi Arabia, pharmacists had a major role in intervening on DDIs in outpatient psychiatry clinics (43). Other studies explained how pharmacists are responsible for identifying DDIs and notifying physicians and patients about the potential consequences (44,45). For safer medication use especially among high risk groups of patients, we believe comprehensive plan to deliver continual professional development courses to pharmacists and physicians as well in outpatient clinics is indispensable.
Our results indicated that more than one-quarter (26.4%) of the dispensed QTcP-inducing drugs were prescribed based on inappropriate decision, and this was significantly associated with urology clinics. A recent study conducted in Germany, found that inappropriate prescribing can lead to negative adverse drug events including QTcP, hyperkalaemia and haemorrhage in patients with kidney diseases (46). Lower rate of inappropriate prescribing was found in the USA (47). Due to inconsistencies in the operational definitions of prescribing appropriateness, results of different studies are barely comparable.
To sum up, patients with ESRD are underrepresented in most of the previous research and as there is no cleared approach for polypharmacy management, clinical assessment of potentially risk factors regarding inappropriate prescribing behaviour, and DDIs monitoring, health officials should efficiently utilised our data to implement concise patient education programme aiming to improve self-monitor of side effects for early detection of potential harm. Furthermore, pharmacists should be encouraged and trained to intervene on DDIs and erroneous medication orders. Further multicentric study to assess the quality of prescribing in hospital settings is required.