Pharmacogenetics: optimising prescribing in primary care

Pharmacogenetic (PGx) testing to personalise prescribing of certain medicines can improve patient outcomes and reduce adverse drug reactions. This article summarises the key findings of the PGx Impact study, designed to estimate the impact of pre-emptive genetic testing on prescribing, and discusses potential ways in which pharmacogenetic testing may optimise primary care prescribing in the near future

Translation and validation of EORTC QLQ-C30 into Indonesian version for cancer patients in Indonesia.

The Indonesian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 can be used as a questionnaire to assess quality of life in Indonesian cancer patients with high-emetogenic treatments

Impact of chemotherapy-induced nausea and vomiting on quality of life in indonesian patients with gynecologic cancer.

Patients reported a negative impact on the QoL of delayed emesis after chemotherapy. Poor prophylaxis of patients' nausea and vomiting after chemotherapy interferes with patients' QoL. Medical and behavioral interventions may help to alleviate the negative consequences of chemotherapeutic treatment in patients with gynecologic cancers treated with suboptimal antiemetics

Estimating the potential impact of implementing pre-emptive pharmacogenetic testing in primary care across the UK

Aims: Pharmacogenetics (PGx) in the UK is currently implemented in secondary care for a small group of high‐risk medicines. However, most prescribing takes place in primary care, with a large group of medicines influenced by commonly occurring genetic variations. The goal of this study is to quantitatively estimate the volumes of medicines impacted by implementation of a population‐level, pre‐emptive pharmacogenetic screening programme for nine genes related to medicines frequently dispensed in primary care in 2019. Methods: A large community pharmacy database was analysed to estimate the national incidence of first prescriptions for 56 PGx drugs used in the UK for the period 1 January–31 December 2019. These estimated prescription volumes were combined with phenotype frequency data to estimate the occurrence of actionable drug–gene interactions (DGI) in daily practice in community pharmacies. Results: In between 19.1 and 21.1% (n = 5 233 353–5 780 595) of all new prescriptions for 56 drugs (n = 27 411 288 new prescriptions/year), an actionable drug–gene interaction (DGI) was present according to the guidelines of the Dutch Pharmacogenetics Working Group and/or the Clinical Pharmacogenetics Implementation Consortium. In these cases, the DGI would result in either increased monitoring, guarding against a maximum ceiling dose or an optional or immediate drug/dose change. An immediate dose adjustment or change in drug regimen accounted for 8.6–9.1% (n = 2 354 058–2 500 283) of these prescriptions. Conclusions: Actionable drug–gene interactions frequently occur in UK primary care, with a large opportunity to optimise prescribing

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting

NO ASSOCIATION OF PARAOXONASE-1 Q192R AND THROMBOTIC EVENTS DURING DUAL ANTI-PLATELET THERAPY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION

Personalised Therapeutic

Effect of gastrointestinal resection on sunitinib exposure in patients with GIST

Background: GIST patients often undergo GI-surgery. Previous studies have shown that imatinib and nilotinib exposures were decreased in GIST patients with prior major gastrectomy. We investigated whether major gastrectomy influences the exposure to sunitinib and its active metabolite SU12662. Methods: Pharmacokinetic data from 305 GIST patients included in 4 phase I-III trials were analyzed. Patients were subdivided into 6 groups according to their prior GI-surgery. Apparent clearance (CL/F) and dose-corrected steady-state plasma exposures (AUC24,ss) of sunitinib and SU12662 were estimated using a population PK approach. ANCOVA was performed to test for differences in AUC24,ss and CL/F between each surgery subgroup and controls. Results: Major gastrectomy did not influence sunitinib or SU12662 exposure. The geometric mean of sunitinib and SU12662 AUC24,ss was decreased by 21% and 28% in patients with both gastrectomy and small bowel resection (n = 8) compared to controls (n = 63) for sunitinib (931 ng*hr/mL (95%-CI; 676–1283) versus 1177 ng*hr/mL (95%-CI; 1097–1263); p < 0.05) and SU12662 (354 ng*hr/mL (95%-CI; 174–720) versus 492 ng*hr/mL (95%-CI; 435–555); p < 0.05). No significant differences in exposure were observed in each of the other subgroups versus controls. Conclusion: In contrast to previous results for imatinib and nilotinib, gastrectomy alone does not influence sunitinib or SU12662 exposure. This should be taken into account for the treatment of gastrectomized GIST patients with TKIs. In patients who had undergone both gastrectomy and small bowel resection, sunitinib and SU12662 exposures are significantly, although clinically not relevantly, decreased

The extent and effects of patient involvement in pictogram design for written drug information : a short systematic review

This short review provides insight into the extent and effectiveness of patient involvement in the design and evaluation of pictograms to support patient drug information. Pubmed, CINAHL, Cochrane Library, Embase, PsycINFO, Academic Search Premier and Web of Science were searched systematically; the 73 included articles were evaluated with the MMAT. We see that, usually, non-patient end-users are involved in the design of pharmaceutical pictograms - patients are more commonly involved in the final evaluation of pictogram success. Repeated involvement of (non-)patients aids the design of effective pharmaceutical pictograms, although there is limited evidence for such effects on patient perception of drug information or health behaviour.Publisher PDFPeer reviewe

Repurposing HLA genotype data of renal transplant patients to prevent severe drug hypersensitivity reactions

Introduction: Specific alleles in human leukocyte antigens (HLAs) are associated with an increased risk of developing drug hypersensitivity reactions induced by abacavir, allopurinol, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, or flucloxacillin. Transplant patients are genotyped for HLA as a routine practice to match a potential donor to a recipient. This study aims to investigate the feasibility and potential impact of repurposing these HLA genotype data from kidney transplant patients to prevent drug hypersensitivity reactions.Methods: A cohort of 1347 kidney transplant recipients has been genotyped in the Leiden University Medical Center (LUMC) using next-generation sequencing (NGS). The risk alleles HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*57:01, and HLA-B*58:01 were retrieved from the NGS data. Medical history, medication use, and allergic reactions were obtained from the patient's medical records. Carrier frequencies found were compared to a LUMC blood donor population.Results: A total of 13.1% of transplant cohort patients carried at least one of the five HLA risk alleles and therefore had an increased risk of drug-induced hypersensitivity for specific drugs. HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01 were found in carrier frequencies of 4.61%, 1.19%, 4.46%, and 3.35% respectively. No HLA-B*15:11 carrier was found. In total nine HLA-B*57:01 carriers received flucloxacillin and seven HLA-B*58:01 carriers within our cohort received allopurinol.Discussion: Our study shows that repurposing HLA genotype data from transplantation patients for the assignment of HLA risk alleles associated with drug hypersensitivity is feasible. The use of these data by physicians while prescribing drugs or by the pharmacist when dispensing drugs holds the potential to prevent drug hypersensitivity reactions. The utility of this method was highlighted by 13.1% of the transplant cohort patients carrying an actionable HLA allele. </p