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Pharmacogenomics (PGx) testing is commonly utilized to predict a patient's response to medications based on the presence of genetic variants. However, certain conditions have been associated with potentially inaccurate PGx results. The majority of medications are predominantly metabolized in the liver; therefore, in the case of liver transplantation, PGx results may be misinterpreted in the context of drug-metabolizing enzymes. Other instances of ambiguous PGx results have been reported in the literature in conditions such as allogeneic stem cell or bone marrow transplant, chronic lymphocytic leukemia, acute or chronic myeloid leukemia and blood transfusion. In order to prevent potential inaccuracies in PGx testing, Sanford Imagenetics developed an active, interruptive alert to inform providers of the potential for inaccurate PGx results.

Background: SLCO1B1 variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. Methods: The authors conducted a retrospective chart review on 20,341 patients who had SLCO1B1 genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. Results: A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.4%) received pharmacotherapy that did not increase risks for SAMS. Providers were more likely to cancel simvastatin orders in response to CDS alerts if genotyping had been done prior to the first simvastatin prescription than after (94.1% vs 28.5%, respectively; p

Background: Statins are among the most commonly prescribed medications, and improve patient outcomes by lowering cholesterol levels, but also have side effects. Variations in statin response can be attributed to a handful of factors that include pharmacogenetics. Methods: While not a true review article, this work was written using various search engines and terms and previous and newly published Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statins to provide a historical perspective in addition to the current status of statin-related pharmacogenetics and future perspectives. Results: This article provides historical background on statins and associated adverse effects, reviews pharmacogenetic implications, applies clinical decision support, incorporates the latest CPIC guidelines and addresses future implications. Conclusion: Statins are a beneficial medication, but not without risk. Pharmacogenomics can help mitigate some risk factors. Clinical decision support, implementation, research and guidelines will continue to influence statin prescribing.

Background: Returning pharmacogenomic (PGx) results to patients is complex and challenging. Patients prefer provider education; however, a gap in provider comfort in PGx results has been documented. Objectives: This study's purpose was to evaluate satisfaction with the return of PGx test results using a patient portal message. Methods: A survey was sent to two cohorts with PGx results, one that received a PGx result message and one that did not. Results: Following implementation of the PGx result message, there was a decrease in patients reporting negative responses surrounding satisfaction in the return of their PGx results, with 39% responding negatively pre-implementation and 21% post-implementation. Conclusion: Satisfaction with the return of results improved following the implementation of a patient portal message.

Aim: Long QT syndrome (LQTS) is an inherited condition that predisposes individuals to prolongation of the QT interval and increased risk for Torsade de Pointes. Pathogenic variants in three genes - KCNH2, KCNQ1 and SCN5A - are responsible for most cases of LQTS, and recent advances in genetic testing have improved knowledge of the disease, increased access to follow-up, and reduced adverse cardiovascular outcomes. Methods: Based around our preemptive genetic screening platform which includes the three long QT genes listed above, we developed and implemented a clinical decision support (CDS) module that alerts prescribers whenever a QT-prolonging medication is ordered for patients with a genetic predisposition to LQTS. Results: Of the 13,777 individuals screened, twenty-seven tested positive for a pathogenic or likely pathogenic variant of KCNH2, KCNQ1 or SCN5A. In a subsequent early evaluation of the CDS and clinical processes, the number of QT-prolonging medications in this cohort decreased by 20% and new QT-prolonging medications were avoided in approximately 1/3 of new prescription orders. Conclusions: While long-term evaluation is needed, early data support the benefit of utilizing CDS in expanded roles, such as drug-gene-disease interactions where rare genetic variants intersect with everyday prescribing.

Metoprolol is a medication commonly utilized in select patients to achieve a reduction in heart rate, systolic blood pressure, or other indications. A majority of metoprolol metabolism occurs via CYP2D6. Decreased expression of the CYP2D6 enzyme increases the concentration of metoprolol. Current pharmacogenomics guidelines by the Dutch Pharmacogenomics Working Group recommend slower titrations and dose decreases to minimize adverse effects from poor metabolizers or normal metabolizers taking concomitant medications that are strong inhibitors of CYP2D6 (phenoconverters). This study aimed to evaluate adverse effects such as bradycardia, hypotension, and syncope in patients who are expected to have absent CYP2D6 enzyme activity due to drug–drug or drug–gene interactions. The secondary aims of this study were to evaluate heart rate measurements for the included participants. Retrospective data were collected for individuals with CYP2D6 genotyping results obtained for clinical purposes. Three categories (CYP2D6 normal metabolizers, poor metabolizers, and phenoconverters) were assigned. A total of 325 participants were included. There was no statistically significant difference found in the primary composite outcome between the three metabolizer groups (p = 0.054). However, a statistically significant difference was identified in the incidences of bradycardia between the poor metabolizers and the normal metabolizers or phenoconverters (p < 0.0001). The average heart rates were 2.8 beats per minute (bpm) and 2.6 bpm lower for the poor metabolizer and phenoconverter groups, respectively, compared to the normal metabolizers (p < 0.0001 for both comparisons). This study further supports the role of genetic testing in precision medicine to help individualize patient care as CYP2D6 poor metabolizers taking metoprolol were found to have an increase in bradycardia. Additional research is needed to clarify the dose relationship in this drug–gene interaction.

Medication reconciliation is recognized as a critically important medication safety element and a key initiative by multiple organizations. Within our precision medicine program, accurate medication lists are essential to our ability to make specific medication recommendations based on pharmacogenetic results. Our study aimed to identify discrepancies within the patient's medication list to improve medication management via genetic factors through a pharmacy team-based approach.A dedicated team of pharmacists and trained student pharmacists conducted telephone interviews to complete medication reconciliation for individuals enrolled in our precision medicine preemptive screening program. Medication list discrepancies were tracked as well as if pharmacogenetic consults were altered by findings during the telephone interviews.Medication reconciliation was completed on 465 participants who had recently received or were awaiting pharmacogenetic testing. We found similar results to previously described rates of medication list discrepancies with an average of 4.9 medication discrepancies per patient as well as greater than 90% of individuals having at least one medication discrepancy. Pharmacogenetic recommendations for 20 individuals (4.3%) required adjustment following medication reconciliation.This pilot program supports the value of a dedicated team for medication reconciliation and the importance of accurate medication lists to optimize precision medicine programs.

Dabigatran etexilate, a direct thrombin inhibitor, has become an alternative to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. There remains a concern about its overdose and life-threatening hemorrhage because of unavailability of appropriate coagulation tests to monitor and antidotes to reverse its effects. There are no clinical data about its safety in patients with fluctuating renal function. Multiple bleeding events reported with dabigatran have prompted the U.S. Food and Drug Administration to further investigate these reports. Four clinical cases with life-threatening bleeding, strategies that were used to achieve hemostasis and a brief literature review to demonstrate the hematologic emergency caused by dabigatran are presented in this study.