Identification of Medication Prescription Errors and Factors of Clinical Relevance in 314 Hospitalized Patients for Improved Multidimensional Clinical Decision Support Algorithms.

Potential medication errors and related adverse drug events (ADE) pose major challenges in clinical medicine. Clinical decision support systems (CDSSs) help identify preventable prescription errors leading to ADEs but are typically characterized by high sensitivity and low specificity, resulting in poor acceptance and alert-overriding. With this cross-sectional study we aimed to analyze CDSS performance, and to identify factors that may increase CDSS specificity. Clinical pharmacology services evaluated current pharmacotherapy of 314 patients during hospitalization across three units of two Swiss tertiary care hospitals. We used two CDSSs (pharmaVISTA and MediQ), primarily for the evaluation of drug-drug interactions (DDI). Additionally, we evaluated potential drug-disease, drug-age, drug-food, and drug-gene interactions. Recommendations for change of therapy were forwarded without delay to treating physicians. Among 314 patients, automated analyses by both CDSSs produced an average of 15.5 alerts per patient. In contrast, additional expert evaluation resulted in only 0.8 recommendations per patient to change pharmacotherapy. For clinical pharmacology experts, co-factors such as comorbidities and laboratory results were decisive for the classification of CDSS alerts as clinically relevant in individual patients in about 70% of all decisions. Such co-factors should therefore be used for the development of multidimensional CDSS alert algorithms with improved specificity. In combination with local expert services, this poses a promising approach to improve drug safety in clinical practice.

Clinical Relevance of a 16-Gene Pharmacogenetic Panel Test for Medication Management in a Cohort of 135 Patients.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study, we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one "actionable" variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4%), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

Evaluation of Incompatible Coadministration of Continuous Intravenous Infusions in a Pediatric/Neonatal Intensive Care Unit.

OBJECTIVES: We aimed to evaluate and quantify incompatible coadministrations of continuous intravenous medication in the daily clinical practice of a PICU/NICU. METHODS: We conducted a retrospective, observational study in the setting of an 18-bed PICU/NICU. All concurrently administered continuous infusions, including blood products and parenteral nutrition, were analyzed for 2 months. Raw electronic data were retrieved and subjected to quality controls. Infusion combinations were classified as compatible, incompatible, no data, or variable according to the internal hospital charts, Trissel's database, and the Swiss summary of product characteristics. For situations with incompatible coadministrations, we assessed alternative distributions of infusions among the currently available lumen. RESULTS: Data for 100 patients were analyzed. Patients were exposed to a mean of 6.9 ± 3.6 individual continuous infusions administered through 3.8 ± 1.8 lumina. Among the 1447 coadministered continuous infusions, we detected 146 incompatible combinations (10%), resulting in 105 individually relevant incompatible situations. Furthermore, 185 combinations (13%) were not covered by internal compatibility charts, and for 207 combinations (15%) no data on compatibility were available. We found that 58% of the incompatible situations could have been avoided by a redistribution of the infusions among the available lumina. CONCLUSIONS: Most infusion combinations in the studied PICU/NICU were compatible and covered by the internal compatibility charts. However, we also identified concurrent administrations of incompatible infusions or for which compatibility data are not available. A significant reduction of coadministrations of incompatible infusions could be achieved through optimal use of available lumina.

Second-generation antipsychotics in a tertiary care hospital: prescribing patterns, metabolic profiles, and drug interactions.

We carried out an observational study that analyzed population characteristics, metabolic profiles, potentially interacting pharmacotherapy, and related adverse events in second-generation antipsychotics (SGAs) users of a tertiary care hospital. Within our pharmacoepidemiological database derived from electronic medical records of 82,358 hospitalizations, we identified 1136 hospitalizations contributing 9165 patient-days with exposure to SGA. Blood pressure, blood glucose, lipids, and BMI had been documented in 97.7, 75.7, 24.6, and 77.4% of hospitalizations, respectively. Among these, the prevalence of hypertension, hyperglycemia, dyslipidemia, and BMI 30 kg/m or more was 36.9, 22.6, 61.1, and 23.1%, respectively. A total of 63.4, 70.8, and 37.1% of SGA users with hyperglycemia, dyslipidemia, and hypertension, respectively, received no pharmacotherapy for these conditions. We identified 614 patient-days with SGA plus formally contraindicated comedication and another 1066 patient-days with other high-risk combinations for QTc prolongation. Among those there was one case with associated neutropenia and four cases with abnormal QTc interval. However, specific monitoring for such adverse events was not documented in 45.5% of hospitalizations with contraindicated and 89.8% with high-risk QTc-prolonging combinations. Our study identified targets for improved monitoring and management in SGA users. These may be implemented as automated alerts into electronic prescribing systems and thereby efficiently support safer pharmacotherapy in clinical practice.

Rivaroxaban postmarketing risk of liver injury.

BACKGROUND & AIMS: Rivaroxaban is an oral direct factor Xa inhibitor that has been marketed worldwide since 2008 for the primary and secondary prevention and treatment of thromboembolic disorders. Although liver injury was observed in premarketing trials of rivaroxaban, there are no published postmarketing cases of liver injury associated with rivaroxaban. METHODS: Report of 14 cases of liver injury associated with rivaroxaban, including two with liver biopsy, and search queries in three large international pharmacovigilance databases for comparable cases. RESULTS: Formal causality assessment classified rivaroxaban as the "highly probable", "probable", and "possible" cause in 4, 7, and 3 patients, respectively. Search results from three large international pharmacovigilance databases revealed a considerable number of additional hepatic adverse events where rivaroxaban was reported as a suspected cause. CONCLUSIONS: We interpret the presented information as a relevant safety signal that should be followed by pharmacoepidemiological studies in order to reliably estimate absolute and relative risks of liver injury associated with rivaroxaban in support of rational risk-benefit assessment. Meanwhile, incident symptoms and signs of liver disease in patients treated with rivaroxaban should be considered as a potential adverse drug reaction, and if no other likely cause can be identified rivaroxaban should be stopped as soon as possible.