United States Emergency Department Use of Medications With Pharmacogenetic Recommendations

Alexander T. Limkakeng Jr, MD; Pratik Manandhar, MS; Alaatin Erkanli, PhD; Stephanie A. Eucker, MD, PhD; Adam Root, PharmD; Deepak Voora, MD


Western J Emerg Med. 2021;22(6):1347-1354. 

In This Article

Abstract and Introduction


Introduction: Emergency departments (ED) use many medications with a range of therapeutic efficacy and potential significant side effects, and many medications have dosage adjustment recommendations based on the patient's specific genotype. How frequently medications with such pharmaco-genetic recommendations are used in United States (US) EDs has not been studied.

Methods: We conducted a cross-sectional analysis of the 2010–2015 National Hospital Ambulatory Medical Care Survey (NHAMCS). We reported the proportion of ED visits in which at least one medication with Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendation of Level A or B evidence was ordered. Secondary comparisons included distributions and 95% confidence intervals of age, gender, race/ethnicity, ED disposition, geographical region, immediacy, and insurance status between all ED visits and those involving a CPIC medication.

Results: From 165,155 entries representing 805,726,000 US ED visits in the 2010–2015 NHAMCS, 148,243,000 ED visits (18.4%) led to orders of CPIC medications. The most common CPIC medication was tramadol (6.3%). Visits involving CPIC medications had higher proportions of patients who were female, had private insurance and self-pay, and were discharged from the ED. They also involved lower proportions of patients with Medicare and Medicaid.

Conclusion: Almost one fifth of US ED visits involve a medication with a pharmacogenetic recommendation that may impact the efficacy and toxicity for individual patients. While direct application of genotyping is still in development, it is important for emergency care providers to understand and support this technology given its potential to improve individualized, patient-centered care.


Drug side effects, toxicity, and limited efficacy are common reasons for treatment failure and non-adherence and can lead to suboptimal outcomes.[1] This can be particularly problematic from the emergency department (ED) where a brief interaction prevents optimal tailoring and adjustments of a patient's medication regimen. One area that holds promise for potentially improving initial choice of treatment is pharmacogenetics. Pharmacogenetics refers to the way in which one or a number of genes influence drug effects. Collectively the study of these relationships comprises pharmacogenomics, the broader study of interactions between numerous genes across the whole genome and drug activity. These genetically determined interactions contribute to the observed variability in different patients' responses to a given drug.

The potential improvement in treatment efficacy and decrease in medication-related morbidity has led the United States Food and Drug Administration to endorse many pharmacogenetic recommendations, ie, altering the dose or choosing an alternate medication for a specific indication based on the patient's genotype. For example, the CYP2D6 gene has numerous alleles with a wide range of function, which can lead to phenotypes ranging from poor to ultrarapid metabolizers of opioids.[2] Up to 28% of patients in some regions of Africa were found to have the ultrarapid metabolizer phenotype for CYP2D6,[3] for which it is recommended to reduce doses of common ED medications such as tramadol, ondansetron, or oxycodone to prevent serious side effects or toxicity.

Excitingly, the ability to apply pharmacogenetic information in the ED may be just on the horizon. Many commercial products allow patients to have their entire genetic data sequenced and downloaded in portable formats, and insurance carriers frequently reimburse for specific genotype tests. This could enable any provider to review their data and provide pharmacogenetic-guided drug selection.[4] Some healthcare systems are already screening and making available to their network providers relevant pharmacogenetic genotypes to help guide clinical care. Once a patient's relevant genotype has been determined, this information can easily be stored in electronic health records (EHR) and used for actionable guidance in real time, similar to existing pop-up warnings for allergic drug reactions.[5,6]

The Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines[7] catalog known pharmacogenetic recommendations into evidence-based recommendations for specific gene–drug pairs. The use of these guidelines can lead to increased efficacy or decreased toxicity from a number of commonly prescribed medications. Therefore, an important first step toward understanding the potential benefit for the application of these guidelines in the ED is to characterize the types and frequencies of medications with pharmacogenetic recommendations that are ordered in EDs in the US. This information could shed light on the potential impact of pharmacogenetic guidance on patient outcomes in the ED.

The US Centers for Disease Control and Prevention National Hospital Ambulatory Medical Care Survey (NHAMCS) allows researchers to calculate nationalized estimates of US ED visit characteristics, including medications ordered and prescribed. We conducted a cross-sectional study using the NHAMCS to determine what proportion of US ED visits included orders for medications with pharmacogenetic recommendations. Secondarily, we sought to determine patient-level characteristics associated with these visits to determine whether there are high-yield subgroups that might benefit from pharmacogenetic genotyping.