Neonatal Abstinence Syndrome and Corresponding Pharmacotherapy Approaches from 2 University-affiliated Neonatal Intensive Care Units in Puerto Rico (2018-2020).

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches. METHODS: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends. RESULTS: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation. CONCLUSION: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.

Warfarin, an oral anticoagulant, has been used for decades to prevent thromboembolic events. The complex interplay between CYP2C9 and VKORC1 genotypes on warfarin PK and PD properties is not fully understood in special sub-groups of patients. This study aimed to externally validate a population pharmacokinetic/pharmacodynamic (PK/PD) model for the effect of warfarin on international normalized ratio (INR) and to evaluate optimal dosing strategies based on the selected covariates in Caribbean Hispanic patients. INR, and CYP2C9 and VKORC1 genotypes from 138 patients were used to develop a population PK/PD model in NONMEM. The structural definition of a previously published PD model for INR was implemented. A numerical evaluation of the parameter-covariate relationship was performed. Simulations were conducted to determine optimal dosing strategies for each genotype combinations, focusing on achieving therapeutic INR levels. Findings revealed elevated IC50 for G/G, G/A, and A/A VKORC1 haplotypes (11.76, 10.49, and 9.22 mg/L, respectively), in this population compared to previous reports. The model-guided dosing analysis recommended daily warfarin doses of 3-5 mg for most genotypes to maintain desired INR levels, although subjects with combination of CYP2C9 and VKORC1 genotypes * 2/* 2-, * 2/* 3- and * 2/* 5-A/A would require only 1 mg daily. This research underscores the potential of population PK/PD modeling to inform personalized warfarin dosing in populations typically underrepresented in clinical studies, potentially leading to improved treatment outcomes and patient safety. By integrating genetic factors and clinical data, this approach could pave the way for more effective and tailored anticoagulation therapy in diverse patient groups.

Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study.

Background: After percutaneous coronary intervention (PCI), clopidogrel resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these ischemic events and improves outcomes among Caribbean Hispanic patients from Puerto Rico, who are underrepresented in clinical pharmacogenomic (PGx)-guided implementation studies. Methods: Individual platelet function testing (PRU) measures, CYP2C19*2 and PON1 rs662 genotypes, clinical and demographic data from 8 medical facilities were included. Patients were separated into standard of care (SoC) and genotype-guided groups (150 each). Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Alternative therapy with ticagrelor was recommended for patients with a high risk score ≥2. Statistical associations between patient time free of MACCEs and predictor variables (i.e., treatment groups, risk scores) were tested in this population using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. Results: Median age of participants is 67 years; BMI: 27.8; 48% women; 14% smokers; 59% with type-2 diabetes mellitus (T2DM). Among patients with high-risk scores who were free from MACCE events 6 months after coronary stenting, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in terms of reducing the incidence rate of atherothrombotic events. Conclusions: The clinical utility of our PGx-driven CDS algorithm to reduce the incidence rate of MACCEs among post-PCI Caribbean Hispanic patients on clopidogrel was externally demonstrated. Clinical Trial Registration Unique Identifier: NCT03419325.

Discovery of Ancestry-specific Variants Associated with Clopidogrel Response among Caribbean Hispanics.

Background: High on-treatment platelet reactivity (HTPR) with clopidogrel is predictive of ischemic events in adults with coronary artery disease. Despite strong data suggesting HTPR varies with ethnicity, including clinical and genetic variables, no genome-wide association study (GWAS) of clopidogrel response has been performed among Caribbean Hispanics. This study aimed to identify genetic predictors of HTPR in a cohort of Caribbean Hispanic cardiovascular patients from Puerto Rico. Methods: Local Ancestry inference (LAI) and traditional GWASs were performed on a cohort of 511 clopidogrel-treated patients, stratified based on their P2Y12 reaction units (PRU) into responders and non-responders (HTPR). Results: The LAI GWAS identified variants within the CYP2C19 region associated with HTPR, predominantly driven by individuals of European ancestry and absent in those with native ancestry. Incorporating local ancestry adjustment notably enhanced our ability to detect associations. While no loci reached traditional GWAS significance, three variants showed suggestive significance at chromosomes 3, 14 and 22 (OSBPL10 rs1376606, DERL3 rs5030613, and RGS6 rs9323567). In addition, a variant in the UNC5C gene on chromosome 4 was associated with an increased risk of HTPR. These findings were not identified in other cohorts, highlighting the unique genetic landscape of Caribbean Hispanics. Conclusion: This is the first GWAS of clopidogrel response in Hispanics, confirming the relevance of the CYP2C19 cluster, particularly among those with European ancestry, and also identifying novel markers in a diverse patient population. Further studies are warranted to replicate our findings in other diverse cohorts and meta-analyses.

Non-Random Enrichment of Single-Nucleotide Polymorphisms Associated with Clopidogrel Resistance within Risk Loci Linked to the Severity of Underlying Cardiovascular Diseases: The Role of Admixture.

Cardiovascular disease (CVD) is one of the leading causes of death in Puerto Rico, where clopidogrel is commonly prescribed to prevent ischemic events. Genetic contributors to both a poor clopidogrel response and the severity of CVD have been identified mainly in Europeans. However, the non-random enrichment of single-nucleotide polymorphisms (SNPs) associated with clopidogrel resistance within risk loci linked to underlying CVDs, and the role of admixture, have yet to be tested. This study aimed to assess the possible interaction between genetic biomarkers linked to CVDs and those associated with clopidogrel resistance among admixed Caribbean Hispanics. We identified 50 SNPs significantly associated with CVDs in previous genome-wide association studies (GWASs). These SNPs were combined with another ten SNPs related to clopidogrel resistance in Caribbean Hispanics. We developed Python scripts to determine whether SNPs related to CVDs are in close proximity to those associated with the clopidogrel response. The average and individual local ancestry (LAI) within each locus were inferred, and 60 random SNPs with their corresponding LAIs were generated for enrichment estimation purposes. Our results showed no CVD-linked SNPs in close proximity to those associated with the clopidogrel response among Caribbean Hispanics. Consequently, no genetic loci with a dual predictive role for the risk of CVD severity and clopidogrel resistance were found in this population. Native American ancestry was the most enriched within the risk loci linked to CVDs in this population. The non-random enrichment of disease susceptibility loci with drug-response SNPs is a new frontier in Precision Medicine that needs further attention.

Local Ancestry-Informed Candidate Pathway Analysis of Warfarin Stable Dose in Latino Populations.

Accuracy of warfarin dose prediction algorithms may be improved by including data from diverse populations in genetic studies of dose variability. Here, we surveyed single nucleotide polymorphisms in vitamin K-related genetic pathways for association with warfarin dose requirements in two admixed Latino populations in standard-principal component adjusted and contemporary-local ancestry adjusted regression models. A total of five variants from vitamin K-related genes/pathways were associated with warfarin dose in both cohorts (P < 0.0125) in standard models. Local ancestry-adjusted analysis unveiled 35 associated variants with absolute effects ranging from ß = 9.04 ( ±2.23) to 39.18 ( ±10.89) per ancestral allele in the discovery cohort and ß = 6.47 (± 2.02) to 17.82 (± 6.83) in the replication cohort. Importantly, we demonstrate the technical validity of the Tractor model in cohorts with admixed ancestry from three founder populations and bring attention to the technical hurdles obstructing the inclusion of diverse, especially admixed, populations in pharmacogenomic research.

Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series.

PURPOSE: Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its impact on the adherence to and outcomes of OUD treatments. The objective of this case series was to describe patient and provider experiences, perceptions, and preferences when said patients were abruptly switched from Suboxone to one of the generic versions manufactured by Sandoz or Alvogen. PATIENTS AND METHODS: A retrospective chart review of 24 Suboxone-maintained OUD patients from a single clinic who were forced to switch to a generic was performed to collect withdrawal and craving symptoms that occurred after the switch, as well as toxicology results and changes in dose (documented by the provider). RESULTS: The medical records of 9 (37.5%) of the 24 patients showed that they were suffering from withdrawal symptoms and/or cravings, had had their doses adjusted, and/or had had a positive urine toxicology screen. All 9 subjects communicated a preference for the brand formulation over that of either of the generic versions; few expressed a preference for one generic formulation over the other. None of patients were able to switch back to the brand formulation, nor were any of them able to choose the generic that worked best for them. Insomnia, muscle pain, and gooseflesh skin were the most common withdrawal symptoms reported by the patients using the generics. Better outcomes were observed in patients who received a buprenorphine dose increase (2 mg) to suppress the withdrawal symptoms experienced while using the generics. CONCLUSION: Our study serves as a reference to prescribers regarding approaches (eg, a small dose adjustment) that may potentially encourage OUD treatment adherence and even improve outcomes in patients who appear to be decompensating after the brand-to-generic switch.

N-Acetyl Cysteine and Glutathione in Health and Cancer-Pharmacogenomics, Research, and Clinical Practice: Hypothesis and Review.

Context: Glutathione (GSH) is a major intracellular antioxidant capable of scavenging free radicals and detoxifying electrophiles from endogenous and exogenous sources via the free thiol group. GSH plays an important role in a multiple cellular process, including cell differentiation, proliferation, and apoptosis. Pharmacogenomics has demonstrated its important role as a key element in cellular health. Objective: The study intended to examine the benefits of using GSH pharmacogenomics as a therapy to prevent side effects and interactions with antineoplastic agents in the diagnosis and treatment of malignancies. Design: The research team performed a narrative review using the Google scholar and PubMed electronic databases. Conclusions: In summary, the involvement of GSH in the carcinogenesis and drug resistance of tumor cells is clear and well understood, but further studies, aimed at understanding the GSH-driven molecular pathways, might be crucial to designing new therapeutic strategies to fight cancer progression, overcoming chemoresistance, using in combination with immunotherapies, and preventing or minimizing their negative side effects.

Machine Learning for Prediction of Stable Warfarin Dose in US Latinos and Latin Americans.

Populations used to create warfarin dose prediction algorithms largely lacked participants reporting Hispanic or Latino ethnicity. While previous research suggests nonlinear modeling improves warfarin dose prediction, this research has mainly focused on populations with primarily European ancestry. We compare the accuracy of stable warfarin dose prediction using linear and nonlinear machine learning models in a large cohort enriched for US Latinos and Latin Americans (ULLA). Each model was tested using the same variables as published by the International Warfarin Pharmacogenetics Consortium (IWPC) and using an expanded set of variables including ethnicity and warfarin indication. We utilized a multiple linear regression model and three nonlinear regression models: Bayesian Additive Regression Trees, Multivariate Adaptive Regression Splines, and Support Vector Regression. We compared each model's ability to predict stable warfarin dose within 20% of actual stable dose, confirming trained models in a 30% testing dataset with 100 rounds of resampling. In all patients (n = 7,030), inclusion of additional predictor variables led to a small but significant improvement in prediction of dose relative to the IWPC algorithm (47.8 versus 46.7% in IWPC, p = 1.43 × 10-15). Nonlinear models using IWPC variables did not significantly improve prediction of dose over the linear IWPC algorithm. In ULLA patients alone (n = 1,734), IWPC performed similarly to all other linear and nonlinear pharmacogenetic algorithms. Our results reinforce the validity of IWPC in a large, ethnically diverse population and suggest that additional variables that capture warfarin dose variability may improve warfarin dose prediction algorithms.

Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally invasive and metastatic cancer. With the objective to reduce cancer metastasis, we developed small molecule inhibitors to target the drivers of metastasis, the Rho GTPases Rac and Cdc42. Of these, MBQ-167 inhibits both Rac and Cdc42 with IC50s of 103 and 78 nmol/L, respectively; and consequently, inhibits p21-activated kinase (PAK) signaling, metastatic cancer cell proliferation, migration, and mammosphere growth; induces cell-cycle arrest and apoptosis; and decreases HER2-type mammary fatpad tumor growth and metastasis (Humphries-Bickley and colleagues, 2017). Herein, we used nuclear magnetic resonance to show that MBQ-167 directly interacts with Rac1 to displace specific amino acids, and consequently inhibits Rac.GTP loading and viability in TNBC cell lines. Phosphokinome arrays in the MDA-MB-231 human TNBC cells show that phosphorylation status of kinases independent of the Rac/Cdc42/PAK pathway are not significantly changed following 200 nmol/L MBQ-167 treatment. Western blotting shows that initial increases in phospho-c-Jun and phospho-CREB in response to MBQ-167 are not sustained with prolonged exposure, as also confirmed by a decrease in their transcriptional targets. MBQ-167 inhibits tumor growth, and spontaneous and experimental metastasis in immunocompromised (human TNBC) and immunocompetent (mouse TNBC) models. Moreover, per oral administration of MBQ-167 at 100 mg/kg body weight is not toxic to immunocompetent BALB/c mice and has a half-life of 4.6 hours in plasma. These results highlight the specificity, potency, and bioavailability of MBQ-167, and support its clinical potential as a TNBC therapeutic.

Pharmacogenomic polygenic risk score for clopidogrel responsiveness among Caribbean Hispanics: A candidate gene approach.

This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on-clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole-genome Infinium MEGA BeadChip array. An ancestry-adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders. The mean PRU across the study cohort was 173.8 ± 68.5 and 33.5% of patients were defined as clopidogrel resistant. Multivariate linear regression showed that 19% of PRU variability was attributed to nine independent predictors, with CYP2C19*2 (rs4244285) accounting for ~ 7% of observed PRU variation (p < 0.001). PON1 rs662, ABCB1/MDR1 rs2032582, PEAR1 rs12041331 carrier status, and the interaction between African ancestry and rs12041331 carriers also predicted PRU among the participants (p ≤ 0.05). A clear gene-dose effect was detected between PRU and CYP2C19*2 genotype, consistent with previous studies in European patient populations, as well as rs12777823. Importantly, a significant positive correlation was detected between our novel wPGxRS (4 variants) and PRU among the Hispanic patient population (rp  = 0.35, p < 0.001). Moreover, the wPGxRS discriminated between nonresponders and responders (p = 0.003), indicating that this multigene-based score is a useful predictor of clopidogrel resistance among Caribbean Hispanics. Taken together, these results help close the gap of knowledge on clopidogrel pharmacogenomics and its potential clinical implementation in this under-represented population.

Personalized health and the coronavirus vaccines-Do individual genetics matter?

Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll-like receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, natural killer cells, T- and B-lymphocytes, and complement. The technology platforms (mRNA, viral vectors, proteins) utilized to produce vaccines against SARS-CoV-2 infections may each trigger genetically distinct immune reactogenic profiles. With DNA biobanking and immunoprofiling of recipients, global COVID-19 vaccinations could launch a new era of personalized healthcare.

PharmVar GeneFocus: CYP2C9.

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C9 gene. Genetic variation within the CYP2C9 gene locus impacts the metabolism or bioactivation of many clinically important drugs, including nonsteroidal anti-inflammatory drugs, phenytoin, antidiabetic agents, and angiotensin receptor blockers. Variable CYP2C9 activity is of particular importance regarding efficacy and safety of warfarin and siponimod as indicated in their package inserts. This GeneFocus provides a comprehensive overview and summary of CYP2C9 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium.

Brand-to-Generic Substitution of Buprenorphine/Naloxone Sublingual Film in Puerto Rico: A Case Study.

A 56-year-old patient with a 1-year history of stable maintenance treatment with Suboxone for opioid use disorder (OUD) was switched to a generic formulation in May of 2019. The patient reported experiencing-over the course of the following 3 months-withdrawal symptoms when switched to the Alvogen-produced generic formulation in May of 2019 and then to the Sandoz-produced version in July of that same year, she also was positive for fentanyl during that time. As a result, the buprenorphine dose was increased, and the patient was stable at this new dose using the generic versions. Blood levels pre- and post-change (not reported in previous case reports) showed maximum buprenorphine concentration being reached more quickly when the brand-name drug was used. Additionally, the area under the curve (AUC) values indicate that the generic formulation had higher exposures than the brand-name drug. Based on the clinical impact of the brand-to generic switch in this patient, further research in this area is warranted. In the meantime, clinicians should carefully monitor their patients so that, if warranted, dose adjustments can be made quickly and safely to minimize negatively impacting the OUD therapy outcomes of patients.

PharmVar GeneFocus: CYP2C19.

The Pharmacogene Variation Consortium (PharmVar) catalogues star (*) allele nomenclature for the polymorphic human CYP2C19 gene. CYP2C19 genetic variation impacts the metabolism of many drugs and has been associated with both efficacy and safety issues for several commonly prescribed medications. This GeneFocus provides a comprehensive overview and summary of CYP2C19 and describes how haplotype information catalogued by PharmVar is utilized by the Pharmacogenomics Knowledgebase and the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Multi-site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos.

We conducted a multi-site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.-1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (ß = -0.29, P < 2.0 × 10-16 ; ß = -0.21, P = 4.7 × 10-7 , respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (ß = 0.10, P = 2 × 10-4 ; ß = 0.10, P = 0.01, respectively). Associations with VKORC1 (ß = -0.14, P = 2.0 × 10-16 ), CYP2C9 (ß = -0.07, P = 5.6 × 10-10 ), and CYP4F2 (ß = 0.03, P = 3 × 10-3 ), but not NQO1*2 (ß = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43-46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin-treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil.

Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico.

BACKGROUND: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. METHODS: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. RESULTS: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0-8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0-8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h-1), distribution (k12= 2.34 h-1, k14 = 1.29 h-1), metabolism (k24 = 1.28 × 10-1 h-1, k23 = 6.43 × 10-2 h-1, k35 = 1.23 × 10-1 h-1, k45 = 8.73 × 10-1 h-1), and elimination (k30 = 3.81 × 10-3 h-1, k50 = 1.27 × 10-1 h-1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. CONCLUSIONS: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico.

A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder.

As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the more complex dosing required of methadone due to its long and variable half-life) and fewer prescribing limitations (may be prescribed outside the setting of federally approved clinics), the increase in buprenorphine use in the United States has been dramatic in recent years. Despite buprenorphine's demonstrated efficacy, patient-specific factors can alter the response to the medications, which may lead to treatment failure in some patients. Clinical characteristics (sex, concurrent medications, and mental health comorbidities) as well as social determinants of health (housing status, involvement with the criminal justice system, and socioeconomic status) may impact treatment outcomes. Furthermore, a growing body of data suggests that genetic variations can alter pharmacological effects and influence therapeutic response. This review will cover the available pharmacogenomic data for the use of buprenorphine in the management of opioid use disorders. Pharmacogenomic determinants that affect opioid receptors, the dopaminergic system, metabolism of buprenorphine, and adverse events are discussed. Although much of the existing data comes from observational studies, clinical research is ongoing. Nevertheless, the development of pharmacogenomic-guided strategies has the potential to reduce opioid misuse, improve clinical outcomes, and save healthcare resources.