489
Views
1
CrossRef citations to date
0
Altmetric
REVIEW

Drug–Drug–Gene Interactions in Cardiovascular Medicine

ORCID Icon & ORCID Icon
Pages 879-911 | Received 23 Aug 2022, Accepted 21 Oct 2022, Published online: 02 Nov 2022

References

  • Ahmad FB, Anderson RN. The leading causes of death in the US for 2020. JAMA. 2021;325(18):1829–1830.
  • GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–1222.
  • Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet. 2009;374(9696):1196–1208.
  • Hahn M, Roll SC. The influence of pharmacogenetics on the clinical relevance of pharmacokinetic drug-drug interactions: drug-gene, drug-gene-gene and drug-drug-gene interactions. Pharmaceuticals. 2021;14(5):32.
  • The Academy of Medical Sciences. Multimorbidity: a priority for global health research; 2018.
  • Tran J, Norton R, Conrad N, et al. Patterns and temporal trends of comorbidity among adult patients with incident cardiovascular disease in the UK between 2000 and 2014: a population-based cohort study. PLoS Med. 2018;15(3):e1002513.
  • Liu G, Xue Y, Liu Y, Wang S, Geng Q. Multimorbidity in cardiovascular disease and association with life satisfaction: a Chinese national cross-sectional study. BMJ Open. 2020;10(12):e042950.
  • Thienemann F, Ntusi NAB, Battegay E, Mueller BU, Cheetham M. Multimorbidity and cardiovascular disease: a perspective on low- and middle-income countries. Cardiovasc Diagn Ther. 2020;10(2):376–385.
  • Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230.
  • Parekh N, Ali K, Stevenson JM, et al. Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK. Br J Clin Pharmacol. 2018;84(8):1789–1797.
  • Cheung JTK, Yu R, Woo J. Is polypharmacy beneficial or detrimental for older adults with cardiometabolic multimorbidity? Pooled analysis of studies from Hong Kong and Europe. Fam Pract. 2020;37(6):793–800.
  • Osanlou R, Walker L, Hughes DA, Burnside G, Pirmohamed M. Adverse drug reactions, multimorbidity and polypharmacy: a prospective analysis of 1 month of medical admissions. BMJ Open. 2022;12(7):e055551.
  • Bruckmueller H, Cascorbi I. Drug-drug-gene interactions: a call for clinical consideration. Clin Pharmacol Ther. 2021;110(3):549–551.
  • Abolhassani N, Vollenweider P, Waeber G, Marques-Vidal P. Ten-year trend in polypharmacy in the Lausanne population. J Patient Saf. 2021;17(4):e269–e273.
  • Malki MA, Pearson ER. Drug-drug-gene interactions and adverse drug reactions. Pharmacogenomics J. 2020;20(3):355–366.
  • Howard RL, Avery AJ, Slavenburg S, et al. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol. 2007;63(2):136–147.
  • Al Hamid A, Ghaleb M, Aljadhey H, Aslanpour Z. A systematic review of hospitalization resulting from medicine-related problems in adult patients. Br J Clin Pharmacol. 2014;78(2):202–217.
  • Kennedy C, Brewer L, Williams D. Drug interactions. Medicine. 2020;48(7):450–455.
  • Magro L, Moretti U, Leone R. Epidemiology and characteristics of adverse drug reactions caused by drug-drug interactions. Expert Opin Drug Saf. 2012;11(1):83–94.
  • Nebert DW. Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist? Clin Genet. 1999;56(4):247–258.
  • McInnes G, Lavertu A, Sangkuhl K, Klein TE, Whirl-Carrillo M, Altman RB. Pharmacogenetics at scale: an analysis of the UK Biobank. Clin Pharmacol Ther. 2021;109(6):1528–1537.
  • Reisberg S, Krebs K, Lepamets M, et al. Translating genotype data of 44,000 biobank participants into clinical pharmacogenetic recommendations: challenges and solutions. Genet Med. 2019;21(6):1345–1354.
  • Van Driest SL, Shi Y, Bowton EA, et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther. 2014;95(4):423–431.
  • Jithesh PV, Abuhaliqa M, Syed N, et al. A population study of clinically actionable genetic variation affecting drug response from the Middle East. NPJ Genom Med. 2022;7(1):10.
  • Mostafa S, Kirkpatrick CMJ, Byron K, Sheffield L. An analysis of allele, genotype and phenotype frequencies, actionable pharmacogenomic (PGx) variants and phenoconversion in 5408 Australian patients genotyped for CYP2D6, CYP2C19, CYP2C9 and VKORC1 genes. J Neural Transm. 2019;126(1):5–18.
  • Ji Y, Skierka JM, Blommel JH, et al. Preemptive pharmacogenomic testing for precision medicine: a comprehensive analysis of five actionable pharmacogenomic genes using next-generation DNA sequencing and a customized CYP2D6 genotyping cascade. J Mol Diagn. 2016;18(3):438–445.
  • Turner RM, de Koning EM, Fontana V, Thompson A, Pirmohamed M. Multimorbidity, polypharmacy, and drug-drug-gene interactions following a non-ST elevation acute coronary syndrome: analysis of a multicentre observational study. BMC Med. 2020;18(1):367.
  • Alshabeeb MA, Deneer VHM, Khan A, Asselbergs FW. Use of pharmacogenetic drugs by the Dutch population. Front Genet. 2019;10:567.
  • Cohn I, Paton TA, Marshall CR, et al. Genome sequencing as a platform for pharmacogenetic genotyping: a pediatric cohort study. NPJ Genom Med. 2017;2:19.
  • Abdullah-Koolmees H, van Keulen AM, Nijenhuis M, Deneer VHM. Pharmacogenetics guidelines: overview and comparison of the DPWG, CPIC, CPNDS, and RNPGx guidelines. Front Pharmacol. 2020;11:595219.
  • Bahar MA, Setiawan D, Hak E, Wilffert B. Pharmacogenetics of drug-drug interaction and drug-drug-gene interaction: a systematic review on CYP2C9, CYP2C19 and CYP2D6. Pharmacogenomics. 2017;18(7):701–739.
  • World Health Organisation. Cardiovascular disease. World Health Organisation; 2021. Available from: https://www.who.int/cardiovascular_diseases/about_cvd/en/. Accessed March 27, 2021.
  • Moran A, Forouzanfar M, Sampson U, Chugh S, Feigin V, Mensah G. The epidemiology of cardiovascular diseases in sub-Saharan Africa: the global burden of diseases, injuries and risk factors 2010 study. Prog Cardiovasc Dis. 2013;56(3):234–239.
  • Koda-Kimble MA, Young LY, Alldredge BK, et al. Applied Therapeutics: The Clinical Use of Drugs. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2009.
  • Cappuccio FP, Miller MA. Cardiovascular disease and hypertension in sub-Saharan Africa: burden, risk and interventions. Intern Emerg Med. 2016;11(3):299–305.
  • Kumar P, Clark M. Clinical Medicine. Elsevier; 2005.
  • Joint Formulary Committee. British National Formulary 80 September 2020 – March 2021; London: BMJ Group and Pharmaceutical Press; 2020: 80
  • Audi S, Burrage DR, Lonsdale DO, et al. The ‘top 100’ drugs and classes in England: an updated ‘starter formulary’ for trainee prescribers. Br J Clin Pharmacol. 2018;84(11):2562–2571.
  • Hales C, Servais J, Martin C, Kohen D. Prescription drug use among adults aged 40–79 in the United States and Canada. NCHS data brief, no 347; 2019. Available from: https://www.cdc.gov/nchs/data/databriefs/db347-h.pdf. Accessed July 7, 2022.
  • ClinCalc DrugStats Database. The Top 300 for 2019; 2021. Available from: https://clincalc.com/DrugStats/Top300Drugs.aspx. Accessed July 20, 2022.
  • Zhang X, Han Y, Huang W, Jin M, Gao Z. The influence of the gut microbiota on the bioavailability of oral drugs. Acta Pharm Sin B. 2021;11(7):1789–1812.
  • Sands CD, Chan ES, Welty TE. Revisiting the significance of warfarin protein-binding displacement interactions. Ann Pharmacother. 2002;36(10):1642–1644.
  • Mullokandov E, Ahn J, Szalkiewicz A, Babayeva M. Protein binding drug-drug interaction between warfarin and tizoxanide in human plasma. Austin J Pharmacol Ther. 2014;2(7):1–3.
  • Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers; 2017. Available from: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Accessed November 18, 2019..
  • Flockhart DA. Drug interactions: cytochrome P450 drug interaction table. Indiana University School of Medicine; 2007. Available from: https://drug-interactions.medicine.iu.edu/MainTable.aspx. Accessed November 18, 2019..
  • Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol. 2013;61(25):2495–2502.
  • BCGuidelines.ca. Use of non-vitamin K antagonist oral anticoagulants (NOAC) in non-valvular atrial fibrillation. Appendix A: potential NOAC drug interaction; 2015. Available from: https://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/anticoag_2015november_full.pdf. Accessed July 14, 2022.
  • Modak AS, Klyarytska I, Kriviy V, Tsapyak T, Rabotyagova Y. The effect of proton pump inhibitors on the CYP2C19 enzyme activity evaluated by the pantoprazole-(13)C breath test in GERD patients: clinical relevance for personalized medicine. J Breath Res. 2016;10(4):046017.
  • Cheng JW, Frishman WH, Aronow WS. Updates on cytochrome p450-mediated cardiovascular drug interactions. Dis Mon. 2010;56(3):163–179.
  • Delaune KP, Alsayouri K. Physiology, Noncompetitive Inhibitor. In: StatPearls. Treasure Island (FL); 2022.
  • Cascorbi I. Drug interactions--principles, examples and clinical consequences. Dtsch Arztebl Int. 2012;109(33–34):546–555; quiz 556.
  • Verbeurgt P, Mamiya T, Oesterheld J. How common are drug and gene interactions? Prevalence in a sample of 1143 patients with CYP2C9, CYP2C19 and CYP2D6 genotyping. Pharmacogenomics. 2014;15(5):655–665.
  • Hocum BT, White JR Jr., Heck JW, et al. Cytochrome P-450 gene and drug interaction analysis in patients referred for pharmacogenetic testing. Am J Health Syst Pharm. 2016;73(2):61–67.
  • Leone R, Magro L, Moretti U, et al. Identifying adverse drug reactions associated with drug-drug interactions: data mining of a spontaneous reporting database in Italy. Drug Saf. 2010;33(8):667–675.
  • Letinier L, Cossin S, Mansiaux Y, et al. Risk of drug-drug interactions in out-hospital drug dispensings in France: results from the DRUG-drug interaction prevalence study. Front Pharmacol. 2019;10:265.
  • Tulner LR, Frankfort SV, Gijsen GJ, van Campen JP, Koks CH, Beijnen JH. Drug-drug interactions in a geriatric outpatient cohort: prevalence and relevance. Drugs Aging. 2008;25(4):343–355.
  • Marzolini C, Elzi L, Gibbons S, et al. Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study. Antivir Ther. 2010;15(3):413–423.
  • Mino-Leon D, Galvan-Plata ME, Doubova SV, Flores-Hernandez S, Reyes-Morales H. Estudio farmacoepidemiológico de potenciales interacciones farmacológicas y sus determinantes, en pacientes hospitalizados [A pharmacoepidemiological study of potential drug interactions and their determinant factors in hospitalized patients]. Rev Invest Clin. 2011;63(2):170–178. Spanish.
  • Zerah L, Henrard S, Wilting I, et al. Prevalence of drug-drug interactions in older people before and after hospital admission: analysis from the OPERAM trial. BMC Geriatr. 2021;21(1):571.
  • Glintborg B, Andersen SE, Dalhoff K. Drug-drug interactions among recently hospitalised patients--frequent but mostly clinically insignificant. Eur J Clin Pharmacol. 2005;61(9):675–681.
  • Obreli-Neto PR, Nobili A, de Oliveira Baldoni A, et al. Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study. Eur J Clin Pharmacol. 2012;68(12):1667–1676.
  • Kohler GI, Bode-Boger SM, Busse R, Hoopmann M, Welte T, Boger RH. Drug-drug interactions in medical patients: effects of in-hospital treatment and relation to multiple drug use. Int J Clin Pharmacol Ther. 2000;38(11):504–513.
  • Reynolds KK, Pierce DL, Weitendorf F, Linder MW. Avoidable drug-gene conflicts and polypharmacy interactions in patients participating in a personalized medicine program. Per Med. 2017;14(3):221–233.
  • Karlgren M, Vildhede A, Norinder U, et al. Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012;55(10):4740–4763.
  • Fettah H, Moutaouakkil Y, Sefrioui MR, et al. Detection and analysis of drug-drug interactions among hospitalized cardiac patients in the Mohammed V Military Teaching Hospital in Morocco. Pan Afr Med J. 2018;29:225.
  • Murtaza G, Khan MY, Azhar S, Khan SA, Khan TM. Assessment of potential drug-drug interactions and its associated factors in the hospitalized cardiac patients. Saudi Pharm J. 2016;24(2):220–225.
  • Kovacevic M, Vezmar Kovacevic S, Miljkovic B, Radovanovic S, Stevanovic P. The prevalence and preventability of potentially relevant drug-drug interactions in patients admitted for cardiovascular diseases: a cross-sectional study. Int J Clin Pract. 2017;71(10):34.
  • Kovacevic M, Vezmar Kovacevic S, Radovanovic S, Stevanovic P, Miljkovic B. Adverse drug reactions caused by drug-drug interactions in cardiovascular disease patients: introduction of a simple prediction tool using electronic screening database items. Curr Med Res Opin. 2019;35(11):1873–1883.
  • Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in cardiac and cardiothoracic intensive care units: an analysis of patients in an academic medical centre in the US. Drug Saf. 2010;33(10):879–888.
  • The Society for Post-Acute and Long-Term Care Medicine. Top 10 particularly dangerous drug interactions in PA/LTC; 2022. Available from: https://paltc.org/top-10-particularly-dangerous-drug-interactions-paltc. Accessed July 19, 2022.
  • Anrys P, Petit AE, Thevelin S, et al. An international consensus list of potentially clinically significant drug-drug interactions in older people. J Am Med Dir Assoc. 2021;22(10):2121–2133.
  • US Food and Drug Administration. Table of pharmacogenetic associations; 2022. Available from: https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations#resources. Accessed July 21, 2022..
  • Klomp SD, Manson ML, Guchelaar HJ, Swen JJ. Phenoconversion of cytochrome P450 metabolism: a systematic review. J Clin Med. 2020;9(9):34.
  • Davis BH, Limdi NA. Translational pharmacogenomics: discovery, evidence synthesis and delivery of race-conscious medicine. Clin Pharmacol Ther. 2021;110(4):909–925.
  • Whirl-Carrillo M, McDonagh EM, Hebert JM, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012;92(4):414–417.
  • Turner RM, Magavern EF, Pirmohamed M. Pharmacogenomics: relevance and opportunities for clinical pharmacology. Br J Clin Pharmacol. 2022. doi:10.1111/bcp.15329
  • Relling MV, Klein TE. CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin Pharmacol Ther. 2011;89(3):464–467.
  • Lee CR, Luzum JA, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022. doi:10.1002/cpt.2526
  • Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017;102(3):397–404.
  • Cooper-DeHoff RM, Niemi M, Ramsey LB, et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin-associated musculoskeletal symptoms. Clin Pharmacol Ther. 2022;111(5):1007–1021.
  • Bahar MA, Lanting P, Bos JHJ, Sijmons RH, Hak E, Wilffert B. Impact of drug-gene-interaction, drug-drug-interaction, and drug-drug-gene-interaction on (es)Citalopram Therapy: the PharmLines Initiative. J Pers Med. 2020;10(4):23.
  • Gschwind L, Rollason V, Boehlen F, et al. Impact of CYP2C9 polymorphisms on the vulnerability to pharmacokinetic drug-drug interactions during acenocoumarol treatment. Pharmacogenomics. 2013;14(7):745–753.
  • Storelli F, Samer C, Reny JL, Desmeules J, Daali Y. Complex drug-drug-gene-disease interactions involving cytochromes p450: systematic review of published case reports and clinical perspectives. Clin Pharmacokinet. 2018;57(10):1267–1293.
  • Meyer Zu Schwabedissen HE, Siegmund W, Kroemer HK, Rollnik JD. Creatine kinase elevation caused by a combination of fluvastatin and telmisartan in a patient heterozygous for the CYP2C9*3 and ABCC2-24C > T variants: a case report. BMC Res Notes. 2014;7:688.
  • Gunes A, Bilir E, Zengil H, Babaoglu MO, Bozkurt A, Yasar U. Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy patients. Basic Clin Pharmacol Toxicol. 2007;100(6):383–386.
  • Fischer TL, Pieper JA, Graff DW, et al. Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers. Clin Pharmacol Ther. 2002;72(3):238–246.
  • Visser LE, van Schaik RH, van Vliet M, et al. Allelic variants of cytochrome P450 2C9 modify the interaction between nonsteroidal anti-inflammatory drugs and coumarin anticoagulants. Clin Pharmacol Ther. 2005;77(6):479–485.
  • Beinema MJ, de Jong PH, Salden HJ, van Wijnen M, van der Meer J, Brouwers JR. The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total Hip replacement surgery. Mol Diagn Ther. 2007;11(2):123–128.
  • Andersson ML, Eliasson E, Lindh JD. A clinically significant interaction between warfarin and simvastatin is unique to carriers of the CYP2C9*3 allele. Pharmacogenomics. 2012;13(7):757–762.
  • Tomisti L, Del Re M, Bartalena L, et al. Effects of amiodarone, thyroid hormones and CYP2C9 and VKORC1 polymorphisms on warfarin metabolism: a review of the literature. Endocr Pract. 2013;19(6):1043–1049.
  • Malhi H, Atac B, Daly AK, Gupta S. Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication. Postgrad Med J. 2004;80(940):107–109.
  • Cheng S, Flora DR, Rettie AE, Brundage RC, Tracy TS. Pharmacokinetic modeling of warfarin capital I, Ukrainian - model-based analysis of warfarin enantiomers with a target mediated drug disposition model reveals CYP2C9 genotype-dependent drug-drug interactions of S-warfarin. Drug Metab Dispos. 2022:3:45.
  • Liu Q, Dang DS, Chen YF, Yan M, Shi GB, Zhao QC. The influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles. Genet Test Mol Biomarkers. 2012;16(11):1293–1297.
  • Furuta T, Iwaki T, Umemura K. Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes. Br J Clin Pharmacol. 2010;70(3):383–392.
  • Depta JP, Lenzini PA, Lanfear DE, et al. Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction. Pharmacogenomics J. 2015;15(1):20–25.
  • Ieiri I, Kimura M, Irie S, Urae A, Otsubo K, Ishizaki T. Interaction magnitude, pharmacokinetics and pharmacodynamics of ticlopidine in relation to CYP2C19 genotypic status. Pharmacogenet Genomics. 2005;15(12):851–859.
  • Chen BL, Chen Y, Tu JH, et al. Clopidogrel inhibits CYP2C19-dependent hydroxylation of omeprazole related to CYP2C19 genetic polymorphisms. J Clin Pharmacol. 2009;49(5):574–581.
  • Hata M, Shiono M, Akiyama K, et al. Incidence of drug interaction when using proton pump inhibitor and warfarin according to cytochrome P450 2C19 (CYP2C19) genotype in Japanese. Thorac Cardiovasc Surg. 2015;63(1):45–50.
  • Uno T, Sugimoto K, Sugawara K, Tateishi T. The role of cytochrome P2C19 in R-warfarin pharmacokinetics and its interaction with omeprazole. Ther Drug Monit. 2008;30(3):276–281.
  • Desmeules JA, Oestreicher MK, Piguet V, Allaz AF, Dayer P. Contribution of cytochrome P-4502D6 phenotype to the neuromodulatory effects of dextromethorphan. J Pharmacol Exp Ther. 1999;288(2):607–612.
  • Pope LE, Khalil MH, Berg JE, Stiles M, Yakatan GJ, Sellers EM. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers. J Clin Pharmacol. 2004;44(10):1132–1142.
  • Eap CB, Lessard E, Baumann P, et al. Role of CYP2D6 in the stereoselective disposition of venlafaxine in humans. Pharmacogenetics. 2003;13(1):39–47.
  • Lessard E, Yessine MA, Hamelin BA, O’Hara G, LeBlanc J, Turgeon J. Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics. 1999;9(4):435–443.
  • Abolfathi Z, Fiset C, Gilbert M, Moerike K, Belanger PM, Turgeon J. Role of polymorphic debrisoquin 4-hydroxylase activity in the stereoselective disposition of mexiletine in humans. J Pharmacol Exp Ther. 1993;266(3):1196–1201.
  • Turgeon J, Fiset C, Giguere R, et al. Influence of debrisoquine phenotype and of quinidine on mexiletine disposition in man. J Pharmacol Exp Ther. 1991;259(2):789–798.
  • Feifel N, Kucher K, Fuchs L, et al. Role of cytochrome P4502D6 in the metabolism of brofaromine. A new selective MAO-A inhibitor. Eur J Clin Pharmacol. 1993;45(3):265–269.
  • Muralidharan G, Hawes EM, McKay G, Korchinski ED, Midha KK. Quinidine but not quinine inhibits in man the oxidative metabolic routes of methoxyphenamine which involve debrisoquine 4-hydroxylase. Eur J Clin Pharmacol. 1991;41(5):471–474.
  • Funck-Brentano C, Turgeon J, Woosley RL, Roden DM. Effect of low dose quinidine on encainide pharmacokinetics and pharmacodynamics. Influence of genetic polymorphism. J Pharmacol Exp Ther. 1989;249(1):134–142.
  • Lessard E, Hamelin BA, Labbe L, O’Hara G, Belanger PM, Turgeon J. Involvement of CYP2D6 activity in the N-oxidation of procainamide in man. Pharmacogenetics. 1999;9(6):683–696.
  • Birgersdotter UM, Wong W, Turgeon J, Roden DM. Stereoselective genetically-determined interaction between chronic flecainide and quinidine in patients with arrhythmias. Br J Clin Pharmacol. 1992;33(3):275–280.
  • Morike KE, Roden DM. Quinidine-enhanced beta-blockade during treatment with propafenone in extensive metabolizer human subjects. Clin Pharmacol Ther. 1994;55(1):28–34.
  • Funck-Brentano C, Kroemer HK, Pavlou H, Woosley RL, Roden DM. Genetically-determined interaction between propafenone and low dose quinidine: role of active metabolites in modulating net drug effect. Br J Clin Pharmacol. 1989;27(4):435–444.
  • Lim KS, Cho JY, Jang IJ, et al. Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects. Br J Clin Pharmacol. 2008;66(5):660–666.
  • Lim KS, Jang IJ, Kim BH, et al. Changes in the QTc interval after administration of flecainide acetate, with and without coadministered paroxetine, in relation to cytochrome P450 2D6 genotype: data from an open-label, two-period, single-sequence crossover study in healthy Korean male subjects. Clin Ther. 2010;32(4):659–666.
  • Funck-Brentano C, Becquemont L, Kroemer HK, et al. Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Clin Pharmacol Ther. 1994;55(3):256–269.
  • Labbe L, O’Hara G, Lefebvre M, et al. Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin Pharmacol Ther. 2000;68(1):44–57.
  • Ujhelyi MR, O’Rangers EA, Fan C, Kluger J, Pharand C, Chow MS. The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine. Clin Pharmacol Ther. 1993;53(1):38–48.
  • Sharma A, Pibarot P, Pilote S, et al. Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. J Pharmacol Exp Ther. 2005;313(3):1172–1181.
  • Sharma A, Pibarot P, Pilote S, et al. Toward optimal treatment in women: the effect of sex on metoprolol-diphenhydramine interaction. J Clin Pharmacol. 2010;50(2):214–225.
  • Hamelin BA, Bouayad A, Methot J, et al. Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clin Pharmacol Ther. 2000;67(5):466–477.
  • Damy T, Pousset F, Caplain H, Hulot JS, Lechat P. Pharmacokinetic and pharmacodynamic interactions between metoprolol and dronedarone in extensive and poor CYP2D6 metabolizers healthy subjects. Fundam Clin Pharmacol. 2004;18(1):113–123.
  • Werner D, Wuttke H, Fromm MF, et al. Effect of amiodarone on the plasma levels of metoprolol. Am J Cardiol. 2004;94(10):1319–1321.
  • Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K. Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clin Pharmacol Ther. 2003;74(2):130–137.
  • Bebawi E, Jouni SS, Tessier AA, Frenette AJ, Brindamour D, Dore M. A metoprolol-terbinafine combination induced bradycardia. Eur J Drug Metab Pharmacokinet. 2015;40(3):295–299.
  • Duricova J, Perinova I, Jurckova N, Kacirova I, Grundmann M. Clinically important interaction between metoprolol and propafenone. Can Fam Physician. 2013;59(4):373–375.
  • Wang Y, Zhou L, Dutreix C, et al. Effects of imatinib (Glivec) on the pharmacokinetics of metoprolol, a CYP2D6 substrate, in Chinese patients with chronic myelogenous leukaemia. Br J Clin Pharmacol. 2008;65(6):885–892.
  • Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br J Clin Pharmacol. 2000;49(6):549–554.
  • Yang WH, Zeng ZS, Ren XW, et al. Simvastatin-induced myopathy with concomitant use of cyclosporine: case report. Int J Clin Pharmacol Ther. 2011;49(12):772–777.
  • Hu M, Mak VW, Tomlinson B. Simvastatin-induced myopathy, the role of interaction with diltiazem and genetic predisposition. J Clin Pharm Ther. 2011;36(3):419–425.
  • Aquilante C, Page R, Brieke A, et al. SLCO1B1 Genotype Influences the Drug-Drug Interaction between Cyclosporine and Pravastatin. J Heart Lung Transplant. 2013;32(4S):S292–S293.
  • Marusic S, Lisicic A, Horvatic I, Bacic-Vrca V, Bozina N. Atorvastatin-related rhabdomyolysis and acute renal failure in a genetically predisposed patient with potential drug-drug interaction. Int J Clin Pharm. 2012;34(6):825–827.
  • Kosuge K, Jun Y, Watanabe H, et al. Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Drug Metab Dispos. 2001;29(10):1284–1289.
  • Michaud V, Mouksassi MS, Labbe L, et al. Inhibitory effects of propafenone on the pharmacokinetics of caffeine in humans. Ther Drug Monit. 2006;28(6):779–783.
  • Dilger K, Greiner B, Fromm MF, Hofmann U, Kroemer HK, Eichelbaum M. Consequences of rifampicin treatment on propafenone disposition in extensive and poor metabolizers of CYP2D6. Pharmacogenetics. 1999;9(5):551–559.
  • Zhu L, Bruggemann RJ, Uy J, et al. CYP2C19 genotype-dependent pharmacokinetic drug interaction between voriconazole and ritonavir-boosted atazanavir in healthy subjects. J Clin Pharmacol. 2017;57(2):235–246.
  • Laine K, Tybring G, Hartter S, et al. Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clin Pharmacol Ther. 2001;70(4):327–335.
  • Kim HS, Lim Y, Oh M, et al. The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes. Br J Clin Pharmacol. 2016;81(2):301–312.
  • Harmsze AM, van Werkum JW, Souverein PC, et al. Combined influence of proton-pump inhibitors, calcium-channel blockers and CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of atherothrombotic events after percutaneous coronary intervention. J Thromb Haemost. 2011;9(10):1892–1901.
  • Tanaka A, Nagamatsu T, Yamaguchi M, et al. Myoclonus after dextromethorphan administration in peritoneal dialysis. Ann Pharmacother. 2011;45(1):e1.
  • Correia RB, de Araújo Kohler LP, Mattos MM, Rocha LM. City-wide electronic health records reveal gender and age biases in administration of known drug–drug interactions. NPJ Digit Med. 2019;2:74.
  • Freshour SL, Kiwala S, Cotto KC, et al. Integration of the Drug-Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts. Nucleic Acids Res. 2021;49(D1):D1144–D1151.
  • Abarca J, Malone DC, Armstrong EP, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc (2003). 2004;44(2):136–141.
  • Olvey EL, Clauschee S, Malone DC. Comparison of critical drug-drug interaction listings: the Department of Veterans Affairs medical system and standard reference compendia. Clin Pharmacol Ther. 2010;87(1):48–51.
  • Vitry AI. Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol. 2007;63(6):709–714.
  • Fung KW, Kapusnik-Uner J, Cunningham J, Higby-Baker S, Bodenreider O. Comparison of three commercial knowledge bases for detection of drug-drug interactions in clinical decision support. J Am Med Inform Assoc. 2017;24(4):806–812.
  • Fulda T, Valuck R, Vander Zanden J, Parker S, Byrns P. Disagreement among drug compendia on inclusion and ratings of drug-drug interactions. Curr Ther Res. 2000;61(8):540–548.
  • Kontsioti E, Maskell S, Bensalem A, Dutta B, Pirmohamed M. Similarity and consistency assessment of three major online drug-drug interaction resources. Br J Clin Pharmacol. 2022. doi:10.1111/bcp.15341
  • Lauschke VM, Zhou Y, Ingelman-Sundberg M. Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity. Pharmacol Ther. 2019;197:122–152.
  • Bank PCD, Caudle KE, Swen JJ, et al. Comparison of the guidelines of the clinical pharmacogenetics implementation consortium and the Dutch pharmacogenetics working group. Clin Pharmacol Ther. 2018;103(4):599–618.
  • Schreiber R, Gregoire JA, Shaha JE, Shaha SH. Think time: a novel approach to analysis of clinicians’ behavior after reduction of drug-drug interaction alerts. Int J Med Inform. 2017;97:59–67.
  • Ahn EK, Cho SY, Shin D, Jang C, Park RW. Differences of reasons for alert overrides on contraindicated co-prescriptions by admitting department. Healthc Inform Res. 2014;20(4):280–287.
  • Bryant AD, Fletcher GS, Payne TH. Drug interaction alert override rates in the Meaningful Use era: no evidence of progress. Appl Clin Inform. 2014;5(3):802–813.
  • Samwald M, Xu H, Blagec K, et al. Incidence of exposure of patients in the United States to multiple drugs for which pharmacogenomic guidelines are available. PLoS One. 2016;11(10):e0164972.
  • Pulley JM, Denny JC, Peterson JF, et al. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther. 2012;92(1):87–95.
  • Crews KR, Hicks JK, Pui CH, Relling MV, Evans WE. Pharmacogenomics and individualized medicine: translating science into practice. Clin Pharmacol Ther. 2012;92(4):467–475.
  • Hoffman JM, Haidar CE, Wilkinson MR, et al. PG4KDS: a model for the clinical implementation of pre-emptive pharmacogenetics. Am J Med Genet C Semin Med Genet. 2014;166C(1):45–55.
  • Weitzel KW, Elsey AR, Langaee TY, et al. Clinical pharmacogenetics implementation: approaches, successes, and challenges. Am J Med Genet C Semin Med Genet. 2014;166C(1):56–67.
  • Nutescu EA, Drozda K, Bress AP, et al. Feasibility of implementing a comprehensive warfarin pharmacogenetics service. Pharmacotherapy. 2013;33(11):1156–1164.
  • Dunnenberger HM, Crews KR, Hoffman JM, et al. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu Rev Pharmacol Toxicol. 2015;55:89–106.
  • Shuldiner AR, Palmer K, Pakyz RE, et al. Implementation of pharmacogenetics: the university of Maryland personalized anti-platelet pharmacogenetics program. Am J Med Genet C Semin Med Genet. 2014;166C(1):76–84.
  • Royal College of Physicians and British Pharmacological Society. Personalised Prescribing: Using Pharmacogenomics to Improve Patient Outcomes. Report of a Working Party. London: Royal College of Physicians and British Pharmacological Society; 2022.
  • Ventola CL. Big data and pharmacovigilance: data mining for adverse drug events and interactions. P T. 2018;43(6):340–351.
  • Bots SH, Groenwold RHH, Dekkers OM. Using electronic health record data for clinical research: a quick guide. Eur J Endocrinol. 2022;186(4):E1–E6.
  • Benchimol EI, Smeeth L, Guttmann A, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med. 2015;12(10):e1001885.
  • Bykov K, Gagne JJ. Generating evidence of clinical outcomes of drug-drug interactions. Drug Saf. 2017;40(2):101–103.
  • McDonough CW. Pharmacogenomics in cardiovascular diseases. Curr Protoc. 2021;1(7):e189.
  • van der Wouden CH, van Rhenen MH, Jama WOM, et al. Development of the PGx-Passport: a panel of actionable germline genetic variants for pre-emptive pharmacogenetic testing. Clin Pharmacol Ther. 2019;106(4):866–873.
  • Meaddough EL, Sarasua SM, Fasolino TK, Farrell CL. The impact of pharmacogenetic testing in patients exposed to polypharmacy: a scoping review. Pharmacogenomics J. 2021;21(4):409–422.
  • Asiimwe IG, Pirmohamed M. Ethnic diversity and warfarin pharmacogenomics. Front Pharmacol. 2022;13:866058.
  • Fatumo S, Chikowore T, Choudhury A, Ayub M, Martin AR, Kuchenbaecker K. A roadmap to increase diversity in genomic studies. Nat Med. 2022;28(2):243–250.
  • Buniello A, MacArthur JAL, Cerezo M, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 2019;47(D1):D1005–D1012.
  • Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update. Clin Pharmacol Ther. 2017;102(3):397–404.
  • Shaw K, Amstutz U, Kim RB, et al. Clinical practice recommendations on genetic testing of CYP2C9 and VKORC1 variants in warfarin therapy. Lippincott Williams & Wilkins; 2015.
  • The Dutch Pharmacogenetics Working Group. CYP2C9; 2016: 1–16. Available from: https://www.g-standaard.nl/risicoanalyse/B0006234.PDF. Accessed January 06, 2022.
  • Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008;84(3):326–331.
  • Klein TE, Altman RB; International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360(8):753–764.
  • Auton A, Brooks LD; Genomes Project C. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.
  • O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213–218.
  • Stouras I, Papaioannou TG, Tsioufis K, Eliopoulos AG, Sanoudou D. The Challenge and Importance of integrating drug-nutrient-genome interactions in personalized cardiovascular healthcare. J Pers Med. 2022;12(4):34.
  • Tod M, Nkoud-Mongo C, Gueyffier F. Impact of genetic polymorphism on drug-drug interactions mediated by cytochromes: a general approach. AAPS J. 2013;15(4):1242–1252.
  • Steelandt J, Jean-Bart E, Goutelle S, Tod M, Prediction A. Model of drug exposure in cirrhotic patients according to Child-Pugh classification. Clin Pharmacokinet. 2015;54(12):1245–1258.
  • Min JS, Bae SK. Prediction of drug-drug interaction potential using physiologically based pharmacokinetic modeling. Arch Pharm Res. 2017;40(12):1356–1379.
  • Johnson D, Wilke MAP, Lyle SM, et al. A systematic review and analysis of the use of polygenic scores in pharmacogenomics. Clin Pharmacol Ther. 2022;111(4):919–930.
  • Pasea L, Chung SC, Pujades-Rodriguez M, et al. Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors. Eur Heart J. 2017;38(14):1048–1055.
  • Malki MA, Dawed AY, Haywood C, Doney A, Pearson ER. Utilizing large electronic medical record data sets to identify novel drug-gene interactions for commonly used drugs. Clin Pharmacol Ther. 2021;110(3):816–825.
  • McInnes G, Altman RB. Drug response pharmacogenetics for 200,000 UK biobank participants. Pac Symp Biocomput. 2021;26:184–195.
  • Shaikh AS, Thomas AB, Chitlange SS. Herb-drug interaction studies of herbs used in treatment of cardiovascular disorders-A narrative review of preclinical and clinical studies. Phytother Res. 2020;34(5):1008–1026.
  • Wang JT. The Polypill at 20 - What have we learned? N Engl J Med. 2022;387(11):1034–1036.
  • van der Wouden CH, Bohringer S, Cecchin E, et al. Generating evidence for precision medicine: considerations made by the Ubiquitous Pharmacogenomics Consortium when designing and operationalizing the PREPARE study. Pharmacogenet Genomics. 2020;30(6):131–144.
  • van der Wouden CH, Cambon-Thomsen A, Cecchin E, et al. Implementing Pharmacogenomics in Europe: design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium. Clin Pharmacol Ther. 2017;101(3):341–358.
  • Blagec K, Swen JJ, Koopmann R, et al. Pharmacogenomics decision support in the U-PGx project: results and advice from clinical implementation across seven European countries. PLoS One. 2022;17(6):e0268534.