Pharmacogenetic Testing Research Articles

CYP3A5 pharmacogenetic testing for tacrolimus in pediatric heart transplant patients: a budget impact analysis.

Pharmacogenomic testing can optimize drug efficacy and minimize adverse effects. CYP3A5 polymorphisms affect the metabolism of tacrolimus. We sought to estimate the budget impact of preemptive pharmacogenomic testing for CYP3A5 in pediatric heart transplantation patients from an institutional perspective. A decision tree was constructed to estimate the budget impact of pediatric heart transplant patients (age ≤18 years) initiated on tacrolimus with and without CYP3A5 pharmacogenomic testing. The budget impact of preemptive pharmacogenomic testing versus no pharmacogenomic testing was calculated. One-way sensitivity analysis and alternative analyses were conducted to assess the robustness of results to changes in model parameters. CYP3A5 genotype-guided dosing provided savings of up to $17 225 per patient compared to standard dosing. These savings decreased to $11 759 when using another institution's data for the standard-dosing group. The time to achieve therapeutic concentration in the poor metabolizer genotype-guided dosing group had the largest impact on cost savings while the cost of the pharmacogenetic test had the smallest impact on cost savings. Implementing CYP3A5 testing could save $17 225 per pediatric heart transplant patient receiving tacrolimus. As pharmacogenomic testing becomes more widespread, institutions should track resource requirements and outcomes to determine the best implementation policies going forward.

Cost-effectiveness analysis of genotype-guided optimization of major depression treatment in Qatar.

Pharmacogenetic testing improves the efficacy and safety of antidepressant pharmacotherapy for moderate-severe major depressive disorder by identifying genetic variations that influence medication metabolism, and adjusting treatment regimens accordingly. This study aims to assess the cost-effectiveness of implementing a pharmacogenetic testing approach to guide the prescription of antidepressants. From the public hospital perspective, we developed a two-stage decision tree diagram of a short-term 6-week follow up, and a lifetime Markov model with 3-month cycles. The analysis compared the current standard of care with the alternative strategy of Pharmacogenetic-guided (multi-gene panel) testing in adult patients with moderate-severe major depressive disorder. Clinical outcomes and utilities were obtained from published studies, while healthcare costs were locally available. The short-term incremental cost-effectiveness ratio was against treatment response without side effects and without relapse, and against treatment response with/without side effects and without relapse. The long-term incremental cost-effectiveness ratio was against the quality-adjusted life year gained and years of life saved. Adopting the pharmacogenetic-guided therapy for adult patients with moderate-severe major depressive disorder in Qatar resulted in cost savings of Qatari Riyal 2,289 (95% confidence interval, -22,654-26,340) for the health system. In the short term, the pharmacogenetic-guided testing was associated with higher response rates without side effects and without relapse (mean difference 0.10, 95% confidence interval 0.09-0.15) and higher response rates with or without side effects and without relapse (mean difference 0.05, 95% confidence interval 0.04-0.06). For long term, the pharmacogenetic-guided testing resulted in 0.13 years of life saved and 0.06 quality-adjusted life year gained, per person, along with cost savings of Qatari Riyal 46,215 (95% confidence interval-15,744-101,758). The sensitivity analyses confirmed the robustness of the model results. Implementing pharmacogenetic testing to guide antidepressant use was found to improve population health outcomes, while also significantly reducing health system costs.

Coadministration of Cariprazine with a Moderate CYP3A4 Inhibitor in Patients with Schizophrenia: Implications for Dose Adjustment and Safety Monitoring.

Cariprazine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. This study aimed to evaluate the effects of erythromycin, a moderate cytochrome P450 (CYP)3A4 inhibitor, on the pharmacokinetics of cariprazine in male patients with schizophrenia, and to assess the influence of CYP2D6 phenotypes on cariprazine metabolism. Forty-two patients received oral doses of 1.5 mg cariprazine alone for 28 days (to reach steady state), followed by a co-administration of cariprazine 1.5 mg daily with erythromycin 500 mg twice daily (BID) and Enterol 250 mg BID for 21 days, followed by a 14-day post-treatment period. Blood samples were collected at predefined time points and analysed for cariprazine, its two active metabolites: desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), and erythromycin using validated high performance liquid chromatography-tandem mass spectrometry methods. CYP2D6 phenotypes were determined by genotyping. The pharmacokinetic parameters were calculated using non-compartmental analysis. Erythromycin increased the area under the curve (AUCτ) and peak concentration (Cmax) of Total cariprazine (cariprazine + DCAR + DDCAR) by about 40-50% but did not affect the time to peak concentration (Tmax). The CYP2D6 phenotypes had no substantial effect on the pharmacokinetics of cariprazine and its metabolites, either alone or in combination with erythromycin. Cariprazine was well tolerated and safe. The findings suggest that co-administration of cariprazine with moderate CYP3A4 inhibitors may require dose adjustment or monitoring; however, pharmacogenetic testing for CYP2D6 is not necessary for optimising cariprazine therapy. Trial registration number (EudraCT Number): 2018-003721-28. Date of registration: 21-SEP-2018.

Pre-Emptive Pharmacogenetic Testing in the Acute Hospital Setting: A Cross-Sectional Study.

Pharmacogenetic guided prescribing can be used to improve the safety and effectiveness of medicines. There are several approaches by which this intervention might be implemented in clinical practice, which will vary depending on the health system and clinical context. To understand the clinical utility of panel-based pharmacogenetic testing in patients admitted acutely to hospital and to establish variables which predict if an individual might benefit from the intervention. A cross-sectional study recruiting patients admitted acutely to hospital. Participants underwent panel-based pharmacogenetic testing and their genetic results were analysed in their context of the medicines they had been exposed to as an inpatient. The primary outcome was the proportion of patients with clinically actionable gene-drug interactions. Individual variables which predict the clinical utility of pharmacogenetic testing were established via logistic regression. Genetic and prescribing data were available for 482 in-patients (55% male; median age 61.2 years; range: 18 to 96), 97.9% of whom carried a pharmacogenetic result of interest. During their admission, 79.5% of patients were exposed to a medicine for which there is pharmacogenetic prescribing guidance available. Just under 1 in 7 individuals (13.7%) had a clinically actionable gene-drug interaction. Increasing age (> 50-years) was positively correlated with the likelihood (2.7-fold increased risk) of having a clinically actionable interaction. These findings demonstrate the potential scale, and potential clinical utility, of pharmacogenetic testing as an intervention, highlighting the need to develop infrastructure to support healthcare professionals make use of this emerging tool.

The influence of age, gender and pharmacogenetic profiles on the perspective on medicines in the German EMPAR study.

Pharmacogenetic testing in routine care could provide benefits for patients, doctors and statutory health insurances. Therefore, the aim of the retrospective, observational study Einfluss metabolischer Profile auf die Arzneimitteltherapiesicherheit in der Routineversorgung (EMPAR) was to analyze the relationship between pharmacogenetic profiles, the risk of adverse drug reactions, and patients' perceptions of drug therapy in 10748 adult (≥18 years) participants in Germany. A questionnaire was used to assess views and beliefs about medicines and participants individual perception of sensitivity to drug therapies. The questionnaire consisted of the Beliefs about Medicines Questionnaire (BMQ)-General scales (Overuse, Harm, Benefit), the Perceived Sensitivity to Medicines (PSM), Natural Remedy, and Gene Testing scales. The influence of gender, age, study collective, genotype and phenotype of relevant pharmacogenes on participant's perception were evaluated. Overuse, PSM and Benefit scores were significantly higher among patients of the collective International Classification of Diseases and Health Related Disorders (ICD)-10 Y57.9! diagnosis, which indicates complications related to drugs, compared to the anticoagulant/antiplatelet and cholesterol-lowering drug collective. Age and gender also played a significant role in patients' perceptions, with younger patients and female participants more likely to believe in medication overuse according to the Overuse scale score compared to older and male participants. Female participants compared to male participants and the old age group compared to the young and/or middle-age subgroup, scored higher in PSM and/or Harm scales, respectively. Only a tendency of increased Harm, Overuse and PSM scores was observed in the participant group with five or more relevant actionable variants compared to subgroups with 0 up to 4 variants. In conclusion, patients' beliefs about medicines and their drug sensitivity perceptions are influenced by various factors including age, gender, previous complications with medicines, and with some tendency also pharmacogenetic profiles. The higher association with more negative views related to treatment indicates that there is a need to target the underlying issues in affected patient groups in order to improve compliance to treatment and outcomes in routine care. Trial registration: EMPAR was registered in the German Clinical Trials Register (DRKS) on 06 July 2018 (DRKS00013909).

Providers'use of pharmacogenetic testing to inform opioid prescribing among veterans.

Aim: To survey Veterans Health Administration providers who prescribed tramadol or codeine to patients with known genotyping for cytochrome 2D6 (CYP2D6) to ascertain awareness of their patient's pharmacogenetic (PGx) test status, whether these results influenced prescribing, perceived benefit of PGx testing, and resources needed to obtain and deliver PGx testing information.Materials & methods: A provider survey was conducted of those who prescribed tramadol or codeine in a patient genotyped for CYP2D6.Results: Of 876 eligible providers, 220 completed the survey. Ten percent were aware that their patient received a PGx test, 64% had not ordered any PGx test related to any medication in the prior year, 55% strongly agreed or agreed that PGx testing is or will be valuable to guide pain medication prescriptions, 29% felt that the evidence base for PGx testing is very strong or moderately strong, 22% responded likely or extremely likely to order a future PGx test, and 51% felt that it would be either very important or fairly important to have a local subject matter expert as a resource for PGx testing.Conclusion: There are modifiable factors that the Veterans Health Administration could address to optimize PGx testing for pain management.

Value of Pharmacogenetic Testing Assessed with Real-World Drug Utilization and Genotype Data.

Implementation of pharmacogenetic testing in clinical care has been slow and with few exceptions is hindered by the lack of real-world evidence on how to best target testing. In this retrospective register-based study, we analyzed a nationwide cohort of 1,425,000 patients discharged from internal medicine or surgical wards and a cohort of 2,178 university hospital patients for purchases and prescriptions of pharmacogenetically actionable drugs. Pharmacogenetic variants were obtained from whole genome genotype data for a subset (n = 930) of the university hospital patients. We investigated factors associated with receiving pharmacogenetically actionable drugs and developed a literature-based cost-benefit model for pre-emptive pharmacogenetic panel testing. In a 2-year follow-up, 60.4% of the patients in the nationwide cohort purchased at least one pharmacogenetically actionable drug, most commonly ibuprofen (25.0%) and codeine (19.4%). Of the genotyped subset, 98.8% carried at least one actionable pharmacogenetic genotype and 23.3% had at least one actionable gene-drug pair. Patients suffering from musculoskeletal or cardiovascular diseases were more prone to receive pharmacogenetically actionable drugs during inpatient episode. The cost-benefit model included frequently dispensed drugs in the university hospital cohort, comprising ondansetron (19.4%), simvastatin (7.4%), clopidogrel (5.0%), warfarin (5.1%), (es)citalopram (5.3%), and azathioprine (0.5%). For untargeted pre-emptive pharmacogenetic testing of all university hospital patients, the model indicated saving €17.49 in direct healthcare system costs per patient in 2 years without accounting for the cost of the test itself. Therefore, it might be reasonable to target pre-emptive pharmacogenetic testing to patient groups most likely to receive pharmacogenetically actionable drugs.

B-221 Combined RT-PCR and Whole Exome Sequencing Pharmacogenetic Testing in Polypharmacy Patient: A Case Report

Abstract Background Pharmacogenetics has become one of the main branches of Precision Medicine owing to its usefulness for patients’s optimal therapeutic management. Notwithstanding, pharmacogenetic testing results must be taken carefully, specially in multimorbidity patients with a variety of drugs prescribed. The aim of the present work is to introduce a combined RT-PCR and Whole Exome Sequencing Approach for pharmacogenetic testing in a patient with multiple drug-related adverse events. Case Background A 67 years old female was derived to our Clinical Chemistry Unit for pharmacogenetic testing due to multiple drug-related adverse events: nifedipine-voriconazole interaction, voriconazole-related neurological toxicity and moxifloxacin-related dizziness. Aditionally, she had been receiving morphine, corticoid for her reumatoid arthritis and antituberculous therapy (r isoniazid / pyrazinamide / rifampin and ethambutol). Methods Patient’s DNA was extracted from a blood sample and undergone by pharmacogenetic testing in two parallel ways: -A first genotyping assay was carried out using Taqman® OpenArray™ PGx Express 120 panel (ThermoFisher™), according to manufacturer’s instructions. -Simultaneusly, in order to cover possible copy number variants and SNPs not covered by our RT-PCR array, a whole exome sequencing run was performed on IlluminaTM NextSeq 1000. Sample library was prepared applying a custom GRCh38 pipeline. Results Relevant variants related to patient’s therapy found by RT-PCR are shown in table 1. SNPs genotyped by RT-PCR were confirmed by NGS. Moreover, whole exome sequencing revealed a deletion in exon 5 of SLCO1B1 gene, which corresponds to SLCO1B1*49 (loss of function); and some variants in NAT2 that may cause toxicity in antituberculous treatment (diplotype NAT2*6C/*7C). Conclusions In those challenging cases that involve multimorbidity and polypharmacy patients, pharmacogenetic testing must be approached taking into account variants that are not covered by the analytical method routinely used and the possibility of complement it with alternative proccedures.

B-222 Receptor-donor CYP3A5 and CYP3A4 genotype testing in liver transplant patients and its influence in tacrolimus blood levels: a retrospective study

Abstract Background Optimal immunosupression is crucial for transplant success. In orthohepatic transplants, blood target levels of tacrolimus, when coadministred with corticoids and mycophenolic acid, are between 6 and 10 ng/mL during the first three months post-transplant. Notwithstanding, achieving tacrolimus concentrations into this range may be tough because of factors such as liver function status, age, sex, drug-drug interactions, etc. In this way, pharmacogenetic testing of CYP3A5 and CYP3A4 genes have demonstrated to be useful in tacrolimus dosing optimization. Nonetheless, there is no evidence enough for pharmacogenetic based adjusting in liver transplant, specially if receptor and graft’s genotypes differ in these loci. The aim of the present study is to find out how the receptor and donor genotypes in CYP3A5 and CYP3A4 genes affect tacrolimus pharmacokinetics. Methods Genotypic profiling of 108 receptor-donor's pairs biopsies gathered from patients who were underwent hepatic transplant from 2012 to 2019 were carried out using Taqman® OpenArray™ PGx Express 120 panel (ThermoFisher™). We focused on CYP3A5*3, *6 and *7; and CYP3A4*1B, *3 and *22 alleles. Next to pharmacogenetic testing, each patient was classified as very poor, poor, intermediate, rapid or ultrarapid metabolizer according to their own genotype, graft’s genotype or both of them. Patient’s initial dose, at seven days after treatment start and after discharge of tacrolimus and their trough concentrations (C0) were collected from their electronic health records. Tacrolimus levels were measured by affinity chrome-mediated immunoassay. C0 was normalized by weight-adjusted dosage (C/D ratio); then, median C/D ratios between different metabolic profiles were compared through Kruskal-Wallis test. Results When patients were classified based on donor’s genotype isolated or combined with receptor’s genotype, lower C/D ratios were found as metabolizer ability increases (p=0.045 for donors and p=0.027 for combined genotypes, respectively). No statistically differences were found for C/D ratios at seven days and discharge, though that differences were almost significant for donor’s genotypes (p=0.06 in both cases). Conclusions These results show that previous information about both patient’s and specially donor’s CYP genes genotype may improve initial immunosupression and avoid tacrolimus induced toxicity. Pharmacogenetics has been currently proposed as a guide for tacrolimus treatment of some solid organ transplants as kidney transplanted patients. Better understanding of how receptor and donor’s CYP genotype affects its pharmacokinetics, along with liver’s damage markers and other genetic polymorphisms will allow clinicians, in the era of personalized medicine, to improve immunosupressive management.

Pharmacogenetic Panel Testing: A Review of Current Practice and Potential for Clinical Implementation.

Pharmacogenetics (PGx) aims to optimize drug treatment outcomes by using a patient's genetic profile for individualized drug and dose selection. Currently, reactive and pretherapeutic single-gene PGx tests are increasingly applied in clinical practice in several countries and institutions. With over 95% of the population carrying at least one actionable PGx variant, and with drugs impacted by these genetic variants being in common use, pretherapeutic or preemptive PGx panel testing appears to be an attractive option for better-informed drug prescribing. Here, we discuss the current state of PGx panel testing and explore the potential for clinical implementation. We conclude that available evidence supports the implementation of pretherapeutic PGx panel testing for drugs covered in the PGx guidelines, yet identification of specific patient populations that benefit most and cost-effectiveness data are necessary to support large-scale implementation.

Can CYP2C19 genotyping improve antiplatelet therapy efficacy in real-life practice? Recent advances.

Clopidogrel remains the most widely used P2Y₁₂ receptor inhibitor worldwide and is often used in combination with aspirin for secondary prevention in patients with arterial disease. The drug is associated with a wide response variability with one on three patients exhibiting little or no inhibition of adenosine diphosphate-induced platelet aggregation. It is a prodrug that is mainly metabolized by hepatic cytochrome P450 (CYP) 2C19. Patients who carry a CYP2C19 loss-of-function (LoF) allele have reduced metabolism of clopidogrel that is associated with reduced platelet inhibition compared to non-carriers that is associated with increased risk for thrombotic event occurrences, particularly, stent thrombosis. The United States Food and Drug Administration (US FDA) issued a black box warning in the clopidogrel label highlighting the importance of presence of CYP2C19 LOF allele during the insufficient metabolism of clopidogrel and availability of other potent P2Y₁₂ inhibitor for the treatment in CYP2C19 poor metabolizers. Clinical trials have conclusively demonstrated greater anti-ischemic benefits of prasugrel/ticagrelor in the treatment of patients carrying the CYP2C19 LoF allele. However, uniform use of these more potent P2Y₁₂ inhibitors has been associated with greater bleeding and cost, and lower adherence. The latter information provides a strong rationale for personalizing P2Y₁₂ inhibitor therapy based on the laboratory determination of CYP2C19 genotype. However, cardiologists have been slow to take up pharmacogenetic testing possibly due to lack of provider and patient education, clear cardiology guidelines and, and lack of positive results from adequately sized randomized clinical trials. However, current evidence strongly supports genotyping of patients who are candidates for clopidogrel. Physicians should strongly consider performing genetic tests to identify LoF carriers and treat these patients with more pharmacodynamically predictable P2Y₁₂ inhibitors than clopidogrel.

Pharmacogenetic Considerations in Beta-Blocker Therapy

Pharmacogenetic testing offers a promising approach to personalizing beta-blocker therapy which is used for a variety of diseases, such as heart failure, myocardial infarction and migraine prophylaxis. The genetic variability in the metabolism and response to beta-blockers such as metoprolol can significantly influence treatment outcomes. Understanding these genetic differences can help optimize therapy and minimize adverse effects. A brief summary of the current guideline and recommendations: Approximately 0.3-6.5% (depending on their ancestry) of patients are CYP2D6 poor metabolizers. CYP2D6 Poor Metabolizers have significantly decreased metabolism of metoprolol, leading to increased drug concentration and a higher risk of adverse effects. The highest dose of metoprolol that patients can tolerate may be lower in CYP2D6 poor metabolizers compared to those that are non-poor CYP2D6 metabolizers. Current evidence is insufficient to support routine clinical testing or therapeutic adjustments for other genes affecting beta-blocker pharmacodynamics, such as ADRB1, ADRB2, ADRA2C, and GRK5. Future research should consider the combined effects of multiple genetic variants (e.g., polygenic risk scores) rather than focusing solely on single-gene associations.

The relevance of pharmacogenetic testing in forensics

The relevance of pharmacogenetic testing in forensics

Implementing Pharmacogenetic Testing as a Risk Reduction Strategy for Drug Users: A Letter to the Editor.

Implementing Pharmacogenetic Testing as a Risk Reduction Strategy for Drug Users: A Letter to the Editor.

Frequency of "Poor Transporter" Phenotype Among Patients with Mental Disorders: Pilot Study

The problem of psychopharmacotherapy safety is actively studied, but remains unresolved, despite the development of new generations of psychotropic drugs (PDs). Neurotoxic adverse drug reactions (ADRs) are one of the leading causes of pseudo-resistance of mental disorders and patient disability. The development of neurotoxic ADRs is genetically determined, and caused by a slowdown in the efflux of PDs from the brain into the blood through the blood-brain barrier. Of the three transport proteins involved in the efflux of PDs, the most clinically significant and studied is glycoprotein P, encoded by the MDR1 (ABCB1) gene. This transport protein is involved in the efflux of a large number of PDs used in real clinical practice of a psychiatrist. Objective: To study the frequency of the non-functional allele 3435T of the single-nucleotide variant rs1045642 of the MDR1 (ABCB1) gene in patients with mental disorders living in the Northwestern region of the Russia. Methods: The study included 71 Caucasians patients with mental disorders (34 male and37 female). Mean age of the study participants was 35.1±16 years). Real-time polymerase chain reaction used for pharmacogenetic testing. Results: The frequency of the nonfunctional homozygous genotype 3435TT (phenotype "poor transporter") was 19.7%, and the frequency of the low-functional heterozygous genotype 3435CT (phenotype "intermediate transporter") was 57.7%. The allelic frequency of T rs1045642 of the MDR1 (ABCB1) gene in Caucasians patients with mental disorders living in the Northwestern region of the Russia was 97.1%. Conclusions: The frequency the nonfunctional allele 3435T of the MDR1 (ABCB1) gene associated with a slowdown in PDs efflux through BBB in patients with mental disorders living in the Northwestern region of the Russia is high, which explains the need for a wider introduction of this method of personalized medicine into real psychiatric practice.

Pharmacogenetics of warfarin: A literature review

Warfarin is an oral indirect anticoagulant that is widely used for the prevention of thromboembolic events. Pharmacogenetic testing is the most promising approach to personalizing warfarin treatment. In this review, we aimed to summarize how the patients’ genetic predispositions affect the pharmacokinetics of warfarin, which determines the different dosing regimens for patients. To correctly interpret data in clinical settings, algorithms for selecting the optimal dosing regimen need to be developed that consider the patient’s age, sex, weight, height, health status, and genetic characteristics. These algorithms could help determine the optimal dose, enhance patient adherence to treatment, and increase the physician’s confidence in the treatment safety. Furthermore, although algorithms that consider SNPs in the CYP2C9, VKORC1, and CYP4F2 genes are more effective in predicting warfarin doses, their effectiveness varies according to race.

Gene-based drug therapy for children and youth treated with psychoactive medications.

Psychoactive medications are increasingly used to treat children and youth with mental health conditions, but individual variations in response highlight the need for precision medicine. Pharmacogenetic (PGx) testing is a key component of precision medicine. The number of commercial pharmacogenetic testing companies promoting PGx, with the promise of achieving individualized and effective treatment of mental health conditions, has grown exponentially in recent years. Scientific evidence supporting the use of PGx to manage mental health conditions is limited, especially for paediatric populations. This practice point outlines steps guiding the use and interpretation of PGx testing for psychoactive medications in clinical settings, along with key supportive resources. Practice guidelines have been developed for variants in pharmacogenes encoding cytochrome P450 drug-metabolizing enzymes (e.g., CYP2C19, CYP2D6, CYP2C9) as one determinant of drug concentrations in blood, which can support both drug choice and dosing strategy for certain anti-psychotics, anti-depressants, and anti-epileptics. Adverse drug reactions to some anti-epileptic drugs (e.g., carbamazepine and phenytoin) have been associated with certain human leukocyte antigen types and variants in DNA polymerase gamma (POLG; valproic acid). Evidence remains limited for genetic variants of drug target proteins, making it challenging to identify patients with altered treatment responses at a therapeutic blood concentration.

Implementation and Evaluation Strategies for Pharmacogenetic Testing in Hospital Settings: A Scoping Review.

Pharmacogenetic testing in clinical settings has improved the safety and efficacy of drug treatment. There is a growing number of studies evaluating pharmacogenetic implementation and identifying barriers and facilitators. However, no review has focused on bridging the gap between identifying barriers and facilitators of testing and the clinical strategies adopted in response. This review was conducted to understand the implementation and evaluation strategies of pharmacogenetic testing programs. A PRISMA-compliant scoping review was conducted. The included studies discussed pharmacogenetic testing programs implemented in a hospital setting. Quantitative, qualitative, and mixed design methods were included. A total of 232 of the 7043 articles that described clinical pharmacogenetic programs were included. The most common specialties that described pharmacogenetic implementation were psychiatry (26%) and oncology (16%), although many studies described institutional programs implemented across multiple specialties (19%). Different specialties reported different clinical outcomes, but all reported similar program performance indicators, such as test uptake and the number of times the test recommendations were followed. There were benefits and drawbacks to delivering test results through research personnel, pharmacists, and electronic alerts, but active engagement of physicians was necessary for the incorporation of pharmacogenetic results into clinical decision making. Further research is required on the maintenance and sustainability of pharmacogenetic testing initiatives. These findings provide an overview of the implementation and evaluation strategies of different specialties that can be used to improve pharmacogenetic testing.

Implementation of a pharmacist-guided pharmacogenomics dosing service at a rural NCI-designated comprehensive cancer center.

The goal of pharmacogenetic testing is to identify genetic variants with significant implications on drug safety and efficacy. Several professional organizations and institutions have demonstrated the value of pharmacist involvement in the implementation of pharmacogenomic services. Therefore, we aimed to establish a pharmacist-guided model for interpretation of pharmacogenetic results for all oncology patients seen at the Dartmouth Cancer Center (DCC) in Lebanon, NH. A pilot of a pharmacist-guided pharmacogenomics dosing service was implemented at the DCC. Pharmacy services included review of results from a next generation sequencing panel for DPYD, TPMT, NUDT15, and UGT1A1 variants. The pharmacist wrote a note in the electronic health record (EHR) detailing actionable drug-gene interactions and drug-dosing guidance, which was then routed to the treating oncologist. Outcomes collected included highlighting actionable mutations and defining pharmacist interventions. In addition, time spent formulating and documenting patient-specific drug-dosing recommendations was collected. From February 2024 through May 2024, a total of 71 patients with pharmacogenetic results, provided by the clinical molecular laboratory at Dartmouth Health, were reviewed by the pharmacist. The majority of patients tested were diagnosed with a malignancy of gastrointestinal origin. Twenty-one patients were found to have actionable variants in at least one of the four genes evaluated, and five of the 21 identified patients had active treatment plans for which dose changes were then implemented. Implementation of a pharmacist-guided pharmacogenomics based dosing service aided in optimizing drug therapy and has positioned Dartmouth Health for further expansion of pharmacogenomics and personalized patient care.

Effect of CYP3A5*3, ABCC2 C-24T, and ABCC2 C3972T Genetic Polymorphisms on Direct Cost of Kidney Transplant Recipients.

Introduction Genetic variations can influence how kidney transplant recipients (KTRs) respond to immunosuppressive drugs. However, limited resources necessitate a cost-benefit analysis of pharmacogenetic testing to determine its role in routine practice. This study investigated the cost-effectiveness of three genetic polymorphisms (CYP3A5*3, ABCC2 -24C>T,andABCC2 3972C>T) in KTRs. Methods This was a multicenter, prospective observational cohort study that included patients on tacrolimus-mycophenolate-prednisolone treatment. Ethnically diverse adult KTRs who had undergone kidney transplantation between 2020 and 2021 and consented were enrolled in the study. Deoxyribonucleic acid(DNA) was extracted from the collected blood samples using a commercially available kit.CYP3A5*3,ABCC2 -24C>T,andABCC2 3972C>Tsingle nucleotide polymorphisms (SNPs) were determined by polymerase chain reaction (PCR). Results Data was analyzed from 39 KTRs with an average age of 32.2 ± 7.0 years. The median annual healthcare cost per patient was MYR 52,700 (laboratory tests and immunosuppressants being the highest expenses). Notably, the annual cost was significantly higher in patients with theCYP3A5*3variant compared to the wildtype (p < 0.001). Furthermore, an incremental cost-effectiveness analysis revealed that carriers of theCYP3A5*1wildtype allele, theABCC2 -24C>T Tvariant allele, and theABCC2 3972C>T Tvariant allele were associated with a more cost-effective approach to kidney transplantation management, potentially reducing the risk of graft rejection and acute tubular necrosis (ATN). Conclusion While these findings suggest potential cost benefits for specific genotypes, further research with larger and more diverse patient populations is necessary to definitively establish the role of pharmacogenetic testing in optimizing cost-effectiveness for KTRs.