Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative

Zajic, Stefan; Jarvis, Joseph P.; Zhang, Pan; Rajula, Kaveri D.; Brangan, Andrew; Brenner, Ruth A.; Dempsey, Michael P.; Christman, Michael F.

doi:10.1097/fpc.0000000000000364

Cited by 10 publications

(8 citation statements)

References 60 publications

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“…Thus, this implementation, through the use of the CDSS, provides the opportunity to improve the safety and efficacy of their usage. Common examples of such medications in this population include ibuprofen [ 42 , 43 ] and omeprazole [ 44 ]. So too, an evaluation of the outcomes of preemptive testing for OTCs in this population may expose additional benefits.…”

Section: Discussionmentioning

confidence: 99%

Real-World Impact of a Pharmacogenomics-Enriched Comprehensive Medication Management Program

Jarvis

Peter

Keogh

et al. 2022

JPM

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The availability of clinical decision support systems (CDSS) and other methods for personalizing medicine now allows evaluation of their real-world impact on healthcare delivery. For example, addressing issues associated with polypharmacy in older patients using pharmacogenomics (PGx) and comprehensive medication management (CMM) is thought to hold great promise for meaningful improvements across the goals of the Quadruple Aim. However, few studies testing these tools at scale, using relevant system-wide metrics, and under real-world conditions, have been published to date. Here, we document a reduction of ~$7000 per patient in direct medical charges (a total of $37 million over 5288 enrollees compared to 22,357 non-enrolled) in Medicare Advantage patients (≥65 years) receiving benefits through a state retirement system over the first 32 months of a voluntary PGx-enriched CMM program. We also observe a positive shift in healthcare resource utilization (HRU) away from acute care services and toward more sustainable and cost-effective primary care options. Together with improvements in medication risk assessment, patient/provider communication via pharmacist-mediated medication action plans (MAP), and the sustained positive trends in HRU, we suggest these results validate the use of a CDSS to unify PGx and CMM to optimize care for this and similar patient populations.

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Section: Discussionmentioning

confidence: 99%

Real-World Impact of a Pharmacogenomics-Enriched Comprehensive Medication Management Program

Jarvis

Peter

Keogh

et al. 2022

JPM

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“…Drugs used for the treatment of acute migraine have relevant adverse effects. NSAIDs are associated with gastrointestinal bleeding, hepatotoxicity, and cardiovascular adverse effects, whereas the most important adverse effects for acetaminophen are hepatotoxicity, allergic reactions, and hematotoxicity ( Zajic et al, 2019 ). Gepants (ubrogepant and rimegepant) are known to be associated with hypersensitivity reactions, nausea, insomnia, dry mouth, and probably hepatotoxicity ( Moreno-Ajona et al, 2020 ; Szkutnik-Fiedler, 2020 ).…”

Section: Important Drug Groups Used For the Treatment Of Headache Dis...mentioning

confidence: 99%

“…Genetic polymorphisms of the mentioned phase one genes, i.e., CYP2C8*3 and CYP2C9 2* and *3 , are responsible for the reduced activity of the enzymes, which potentially lead to higher plasma levels of NSAIDs and, thus, stronger adverse effects of these drugs ( Dorado et al, 2008 ; Figueiras et al, 2016 ; Zajic et al, 2019 ; Blanco et al, 2008 ). The mentioned genetic variants have been associated with an increased risk of adverse effects, including hepatotoxicity and gastrointestinal bleeding ( Figueiras et al, 2016 ; Zajic et al, 2019 ; Blanco et al, 2008 ; McEvoy et al, 2021 ) ( Table 3 ). Genetic polymorphisms in the genes coding for UDP-glucuronosyltransferases that are responsible for the conjugation of NSAID metabolites may also be associated with impaired clearance of NSAIDs.…”

Section: Pharmacogenetics Of Important Drugs Used In Migraine Tension...mentioning

confidence: 99%

Pharmacogenetics in Primary Headache Disorders

et al. 2022

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Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin–angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders.

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“…NSAIDs are recommended in all ERAS pathways for their analgesic effects and minimal potential for addiction but are also associated with potentially deleterious effects on the gastrointestinal, cardiovascular, and renal systems. Multiple studies have linked decreased CYP2C9 function with elevated NSAID exposure and risk of toxicity and adverse events [100][101][102]. The CPIC recently published recommendations and guidelines for initiation and titration of NSAIDs based on individual medical history and CYP2C9 phenotype [103].…”

Section: Cyp2c9mentioning

confidence: 99%

A Narrative Review on Perioperative Pain Management Strategies in Enhanced Recovery Pathways—The Past, Present and Future

Chen¹,

Chen²,

Xiang³

2021

JCM

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Effective pain management is a key component in the continuum of perioperative care to ensure optimal outcomes for surgical patients. The overutilization of opioids in the past few decades for postoperative pain control has been a major contributor to the current opioid epidemic. Multimodal analgesia (MMA) and enhanced recovery after surgery (ERAS) pathways have been repeatedly shown to significantly improve postoperative outcomes such as pain, function and satisfaction. The current review aims to examine the history of perioperative MMA strategies in ERAS and provide an update with recent evidence. Furthermore, this review details recent advancements in personalized pain medicine. We speculate that the next important step for improving perioperative pain management could be through incorporating these personalized metrics, such as clinical pharmacogenomic testing and patient-reported outcome measurements, into ERAS program.

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Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative

Cited by 10 publications

References 60 publications

Real-World Impact of a Pharmacogenomics-Enriched Comprehensive Medication Management Program

Real-World Impact of a Pharmacogenomics-Enriched Comprehensive Medication Management Program

Pharmacogenetics in Primary Headache Disorders

A Narrative Review on Perioperative Pain Management Strategies in Enhanced Recovery Pathways—The Past, Present and Future

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