Munir Pirmohamed

Munir Pirmohamed
University of Liverpool | UoL · Department of Molecular and Clinical Pharmacology

PhD, FRCP(E), FRCP, FMedSci

About

952
Publications
181,228
Reads
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45,004
Citations
Citations since 2016
314 Research Items
22682 Citations
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Additional affiliations
January 2011 - present
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
January 2011 - present
January 2010 - present
Tel Aviv University

Publications

Publications (952)
Article
Full-text available
Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal and financial burden due to inefficacy and adverse reactions to drugs. However, such implementation is lagging in many parts of the world, including the Middle East, mainly due to the lack of data on the distribution of actionable ph...
Article
Full-text available
Since the first polygenic risk score (PRS) in 2007, research in this area has progressed significantly. The increasing number of SNPs that have been identified by large scale GWAS analyses has fuelled the development of a myriad of PRSs for a wide variety of diseases and, more recently, to PRSs that potentially identify differential response to spe...
Article
Background: High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts. Methods: Information was obtained from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiol...
Article
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β-Lactamase inhibitors such as clavulanic acid and tazobactam were developed to overcome β-lactam antibiotic resistance. Hypersensitivity reactions to these drugs have not been studied in detail, and the antigenic determinants that activate T-cells have not been defined. The objectives of this study were to (i) characterize clavulanate- and tazobac...
Article
Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in G6PD deficient persons, but in many cases, this information is conflicting, and the...
Article
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Diversity in pharmacogenomic studies is poor, especially in relation to the inclusion of black African patients. Lack of funding and difficulties in recruitment, together with the requirement for large sample sizes because of the extensive genetic diversity in Africa, are amongst the factors which have hampered pharmacogenomic studies in Africa. Wa...
Article
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Objective To ascertain the burden and associated cost of adverse drug reactions (ADRs), polypharmacy and multimorbidity through a prospective analysis of all medical admissions to a large university teaching hospital over a 1-month period. Design Prospective observational study. Setting Liverpool University Hospital Foundation National Health Ser...
Article
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Introduction Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, longterm cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV). Pharmacovigilance—monitoring the effects of medicines—is essential for unders...
Article
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Background: The clinical implementation of pharmacogenomics (PGx) could be one of the first milestones towards realizing personalized medicine in routine care. However, its widespread adoption requires the availability of suitable clinical decision support (CDS) systems, which is often impeded by the fragmentation or absence of adequate health IT...
Article
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Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of geno...
Conference Paper
Introduction Non-alcoholic fatty liver disease (NAFLD) is a complex trait disorder. Genome-wide association studies (GWAS) of MRI hepatic image phenotypes and health records may allow identification of single nucleotide polymorphisms (SNPs) associated with NAFLD. In this study, we have used the UK Biobank to identify potential genetic risk factors...
Article
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Objectives To examine the socioeconomic and demographic drivers associated with polypharmacy (5–9 medicines), extreme polypharmacy (9–20 medicines) and increased medication count. Design, setting and participants A total of 5509 participants, from two waves of the English North West Coast, Household Health Survey were analysed Outcome measures Lo...
Article
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Warfarin has remained the most commonly prescribed vitamin K oral anticoagulant worldwide since its approval in 1954. Dosing challenges including having a narrow therapeutic window and a wide interpatient variability in dosing requirements have contributed to making it the most studied drug in terms of genotype-phenotype relationships. However, mos...
Article
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Aim: To explore the level of agreement on drug-drug interaction (DDI) information listed in three major online drug information resources (DIRs) in terms of: (1) interacting drug pairs; (2) severity rating; (3) evidence rating and (4) clinical management recommendations. Methods: We extracted information from the British National Formulary (BNF)...
Article
Purpose: Bisoprolol is a widely used beta-blocker in patients with cardiovascular diseases. As with other beta-blockers, there is variability in response to bisoprolol, but the underlying reasons for this have not been clearly elucidated. Our aim was to investigate genetic factors that affect bisoprolol pharmacokinetics (PK) and pharmacodynamics (...
Article
BACKGROUND & AIMS Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10...
Article
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Aims: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). Methods: More than 500 databases were searched between 1-Nov-2020 and 2-Oct-2021 to identify RCTs that were publish...
Article
Hypersensitivity reactions are caused by many structurally unrelated drugs used for many different diseases. These reactions vary in severity and can be fatal. Only a minority of patients are affected by drug hypersensitivity reactions. Predisposition seems to be mediated by genetic factors, particularly within the HLA system. Apart from HLA-B∗57:0...
Preprint
Aims: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). Methods: More than 500 databases were searched between 1-Nov-2020 and 2-Oct-2021 to identify RCTs that were published...
Article
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Teicoplanin is a glycopeptide antibiotic deployed to combat Gram-positive bacterial infection and has recently been associated with development of adverse drug reactions, particularly following previous exposure to vancomycin. In this study, we generated teicoplanin-specific monoclonal T-cell populations from healthy volunteers expressing HLA-A*32:...
Article
Background: Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes but circulating 25-hydroxyvitamin D (25(OH)D) is largely bound to vitamin D binding protein (DBP) or albumin both of which tend to fall in illness making 25(OH)D status hard to interpret. Because of this, measurement of unbound "free" and a...
Article
Human leukocyte antigen (HLA) is a hallmark genetic marker for the prediction of certain immune-mediated adverse drug reactions (ADRs). Numerous basic and clinical research studies have provided the evidence base to push forward the clinical implementation of HLA testing for the prevention of such ADRs in susceptible patients. This review explores...
Article
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Background Low-dose aspirin can cause gastric and duodenal ulceration, hereafter called peptic ulcer disease (PUD). Predisposition is thought to be related to clinical and genetic factors; our aim was to identify genetic risk factors associated with aspirin-induced PUD. Methods Patients (n=1478) were recruited from 15 UK hospitals. Cases (n=505) w...
Chapter
Sequential rule mining is a well-established data mining technique for binary valued data. Many variations have been proposed, most approaches use the support-confidence-lift framework. Existing approaches make assumptions concerning the definition of what a sequence is. However, this definition is application dependent. In this paper we look at se...
Article
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Warfarin remains the most widely prescribed oral anticoagulant in sub‐Saharan Africa. However, because of its narrow therapeutic index, dosing can be challenging. We have therefore (a) evaluated and compared the performance of 21 machine‐learning techniques in predicting stable warfarin dose in sub‐Saharan Black‐African patients and (b) externally...
Article
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An emerging clinical issue associated with immune-oncology agents is the collateral effects on the tolerability of concomitant medications. One report of this phenomenon was the increased incidence of hypersensitivity reactions observed in patients receiving concurrent immune checkpoint inhibitors and sulfasalazine. Thus, the aim of this study was...
Article
There is an evolution and increasing need for the utilization of emerging cellular, molecular and in silico technologies and novel approaches for safety assessment of food, drugs, and personal care products. Convergence of these emerging technologies is also enabling rapid advances and approaches that may impact regulatory decisions and approvals....
Article
Currently no sensitive and specific biomarkers exist to predict drug‐resistant epilepsy. We determined whether blood levels of high‐mobility group box 1 (HMGB1), a mediator of neuroinflammation implicated in drug‐resistant epilepsies, identifies patients with drug‐resistant seizures. Patients with drug‐resistant epilepsy express significantly highe...
Article
Background & Aims Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. Methods Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10...
Preprint
BACKGROUND Adult chronic heart failure mainly affects an elderly population with multiple co-morbidities that often require frequent medical visits to prevent poor health outcomes. However the heart failure disease process reduces their independence by reducing mobility, exercise tolerance and cognitive decline. Remote care technologies can bridge...
Article
Full-text available
Background: Adult chronic heart failure mainly affects an elderly population with multiple comorbidities that often require frequent medical visits to prevent poor health outcomes. However, the heart failure disease process reduces their independence by reducing mobility, exercise tolerance, and cognitive decline. Remote care technologies can brid...
Article
Pharmacogenomics promises to advance cardiovascular therapy, but there remain pragmatic barriers to implementation. These are particularly important to explore within Europe, as there are differences in the populations, availability of resources and expertise, as well as in ethico-legal frameworks. Differences in healthcare delivery across Europe p...
Article
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Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A genome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was...
Article
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Background There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pr...
Article
Full-text available
Drug rash with eosinophilia with systemic symptoms (DRESS) is a serious adverse event associated with use of the glycopeptide antibiotic vancomycin. Vancomycin-induced DRESS is associated with the expression of HLA-A*32:01, suggesting that the drug interacts with this HLA to activate CD8+ T-cells. The purpose of this study was to utilize PBMC from...
Article
Full-text available
The relationship between the genetic loci that influence mean corpuscular volume (MCV) and those associated with excess alcohol drinking are unknown. We used white British participants from the UK Biobank (n = 362 595) to assess the association between alcohol consumption and MCV, and whether this was modulated by genetic factors. Multivariable reg...
Article
Full-text available
Aims: To continually evaluate the association between cardiovascular drug exposure and COVID-19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all-cause mortality) in patients at risk of/with confirmed COVID-19. Methods: Eligible publications were identified from >500 databases on 1...
Article
Full-text available
Pharmacogenomics has a burgeoning role in cardiovascular medicine, from warfarin dosing to antiplatelet choice, with recent developments in sequencing bringing the promise of personalised medicine ever closer to the bedside. Further scientific evidence, real-world clinical trials, and economic modelling are needed to fully realise this potential. A...
Article
Full-text available
Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug rea...
Article
Full-text available
HLA-B*13:01 allele has been identified as the genetic determinant of dapsone hypersensitivity syndrome (DHS) among leprosy and non-leprosy patients in several studies. Dapsone hydroxylamine (DDS-NHOH), an active metabolite of dapsone, has been believed to be responsible for DHS. However, studies have not highlighted the importance of other genetic...
Article
Full-text available
Many adverse reactions associated with immune checkpoint inhibitor (ICI) treatments are immunologically driven and may necessitate discontinuation of the ICI. Herein, we present a patient who had been administered the radio contrast media amidotrizoate multiple times without issue but who then developed a Stevens-Johnson syndrome reaction after coa...
Article
Full-text available
HLA-B*13:01 -positive patients in Thailand can develop frequent co-trimoxazole hypersensitivity reactions. This study aimed to characterize drug-specific T cells from three co-trimoxazole hypersensitive patients presenting with either Stevens-Johnson syndrome or drug reaction with eosinophilia and systemic symptoms. Two of the patients carried the...
Article
Full-text available
Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation resp...
Preprint
Full-text available
Background: There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a p...
Article
HLA-B*13:01 is associated with dapsone (DDS)-induced hypersensitivity and it has been shown that CD4+ and CD8+ T cells are activated by DDS and its nitroso metabolite (DDS-NO). However, there is a need to define the importance of the HLA association in the disease pathogenesis. Thus, DDS and DDS-NO-specific CD8+ T cell clones (TCC) were generated f...
Article
There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation and application of such data, nor is there recognition of the challenges of variation in c...
Article
Full-text available
Background Understanding the relationship between occupation and alcohol use offers opportunities to provide health promotion programmes based on evidence of need. We aimed to determine associations between occupation and heavy alcohol consumption in working individuals aged 40–69 years. Methods A cross-sectional study was conducted using 100,817...
Article
Full-text available
Patients in sub‐Saharan Africa generally have poor anticoagulation control. We review the potential reasons for this poor control, as well as the potential solutions. Challenges include the affordability and centralisation of anticoagulation care, problems with access to medicines and INR monitoring, the lack of locally‐validated standardized dosin...
Article
Full-text available
Warfarin has existed for more than seven decades and has been the anticoagulant of choice for many thromboembolic disorders. The recent introduction of direct acting oral anticoagulants (DOACs) has however caused a shift in preference by healthcare professionals all over the world. DOACs have been found to be at least as effective as warfarin in pr...
Article
Recent advances in the understanding of depression have led to increasing interest in ketamine and the role that N-methyl-d-aspartate (NMDA) receptor inhibition plays in depression. l-4-Chlorokynurenine (4-Cl-KYN, AV-101), a prodrug, has shown promise as an antidepressant in preclinical studies, but this promise has not been realized in recent clin...
Chapter
Oncology has been at the vanguard of pharmacogenomics for a number of years. Indeed, a significant number of clinically utilized genetic tests for predicting safety or efficacy are for ant-cancer drugs. This chapter describes some key examples of clinically utilized pre-emptive tests for pharmacogenomic variants, which can predict patient oncology...
Article
Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities. Our aim was to analyse trends and inequalities in uptake of testing, and identify predictors...
Article
Rationale: Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite IC...
Article
Warfarin remains the oral anticoagulant of choice in sub‐Saharan Africa. However, dosing is challenging due to a highly variable clinical response for a given dose. This study aimed to develop and validate a clinical warfarin dose‐initiation model in sub‐Saharan Black‐African patients. For the development cohort, we used data from 364 patients who...
Article
Full-text available
Most of the prescribing and dispensing of medicines happens in primary care. Pharmacogenomics (PGx) is the study and clinical application of the role of genetic variation on drug response. Mounting evidence suggests PGx can improve the safety and/or efficacy of several medications commonly prescribed in primary care. However, implementation of PGx...
Article
Full-text available
Background The number of patients living with co-existing diseases is growing. This study aimed to assess the extent of multimorbidity, medication use, and drug- and gene-based interactions in patients following a non-ST elevation acute coronary syndrome (NSTE-ACS). Methods In 1456 patients discharged from hospital for a NSTE-ACS, comorbidities an...
Article
Full-text available
Aims: Carbamazepine can cause hypersensitivity reactions in ~10% of patients. An immunogenic effect can be produced by the electrophilic 10,11-epoxide metabolite but not by carbamazepine. Hypothetically, certain single nucleotide polymorphisms might increase the formation of immunogenic metabolites, leading ultimately to hypersensitivity reactions...