Hospital admissions for bleeding events associated with treatment with apixaban, dabigatran and rivaroxaban.

OBJECTIVES: To analyse the hospital admissions for bleeding events associated with treatment with direct oral anticoagulants (DOACs). To describe the characteristics and outcomes of those patients. METHODS: A retrospective observational study was carried out in the framework of an integral risk management plan of drugs and proactive pharmacovigilance of hospital admissions for bleeding associated with apixaban, dabigatran and rivaroxaban from April 2015 through December 2016. Cases were identified using the information management tool of Orion Clinic (hospital electronic medical history) and by reviewing the hospital discharge reports. Various biometric, clinical and pharmacotherapeutic variables of each patient were registered. RESULTS: 37 hospitalisation episodes for DOAC-induced bleeding in 32 patients (15 received rivaroxaban, 9 apixaban and 8 dabigatran) were detected, representing an incidence rate of 3.44 per 100 person-years (95% CI 2.35 to 4.86). The most common bleeding site was gastrointestinal (27 cases, 73.0%). Intracranial bleeding was rare (three cases, 8.1%). Four patients (12.5%) were receiving DOACs at full doses and had a 'dose reduction indication'. The mean (SD) length of stay was 8.4 (5.2) days. Three patients (8.1%) died during the hospitalisation. Among bleeding episodes without fatal outcome, DOACs were stopped in 14 cases, continued in 14 cases, switched for another DOAC in two cases and the dose was reduced in four cases. CONCLUSIONS: DOACs are associated with serious bleeding events that require hospitalisation. The risk/benefit ratio assessment considering patient preferences and an individualised follow-up, especially in patients who are elderly, polymedicated or have impaired renal function, can help to reinforce the safe use of DOACs.

Cross-sectional analysis of retrospective case series of hospitalisations for gastropathy caused by non-steroidal anti-inflammatory treatment: risk factors and gastroprotection use.

OBJECTIVES: To analyse the risk factors of gastropathy caused by using non-steroidal anti-inflammatory drugs (NSAIDs) in detected hospital admissions and to analyse the use of gastroprotective treatment concerning these risk factors. METHODS: A retrospective observational study was carried out in the framework of an integral risk management plan of drugs and proactive pharmacovigilance of hospital admissions for NSAID-induced gastropathy occurring between 2011 and 2015. Cases were identified after reviewing the ICD-9 codes related to NSAID-induced gastropathy in hospital discharge reports. Various biometric, clinical and pharmacotherapeutic variables of each patient were registered. The gastroprotective criteria set out in the therapeutic decision algorithm of the Valencian Health System were followed. RESULTS: 62 hospital admissions for NSAID-induced gastropathy were detected. The mean length of stay was 5.3±3.8 days. Ibuprofen was the most prevalent NSAID (28 cases, 45.2%). 24 cases (38.7%) took NSAIDs in the week before hospitalisation. The prevalence of relevant risk factors for gastropathy were age >60 years (37 cases, 59.7%), concomitant medication (24 cases, 38.7%) and a history of peptic ulcer (9 cases, 14.5%). 41 patients (66.1%) met gastroprotective major criteria, 18 of whom (43.9%) were using a proton pump inhibitor following a prevention plan. CONCLUSIONS: In this study all relevant gastroprotective criteria were associated with the use of gastroprotection in detected hospital admissions for NSAID-induced gastropathy. However, a lack of gastroprotection was observed in a large number of detected cases with the criteria to use it. The feedback of our results to health area agents can serve to reinforce the safe use of NSAIDs.

Population pharmacokinetic model of lithium and drug compliance assessment.

Population pharmacokinetic analysis of lithium during therapeutic drug monitoring and drug compliance assessment was performed in 54 patients and 246 plasma concentrations levels were included in this study. Patients received several treatment cycles (1-9) and one plasma concentration measurement for each patient was obtained always before starting next cycle (pre-dose) at steady state. Data were analysed using the population approach with NONMEM version 7.2. Lithium measurements were described using a two-compartment model (CL/F=0.41Lh-1, V1/F=15.3L, Q/F=0.61Lh-1, and V2/F = 15.8L) and the most significant covariate on lithium CL was found to be creatinine clearance (reference model). Lithium compliance was analysed using inter-occasion variability or Markovian features (previous lithium measurement as ordered categorical covariate) on bioavailability parameter. Markov-type model predicted the lithium compliance in the next cycle with higher success rate (79.8%) compared to IOV model (65.2%) and reference model (43.2%). This model becomes an efficient tool, not only being able to adequately describe the observed outcome, but also to predict the individual drug compliance in the next cycle. Therefore, Bipolar disorder patients can be classified regarding their probability to become extensive or poor compliers in the next cycle and then, individual probabilities lower than 0.5 highlight the need of intensive monitoring, as well as other pharmaceutical care measurements that might be applied to enhance drug compliance for a better and safer lithium treatment.