Use of Pharmacogenomics to Guide Proton Pump Inhibitor Therapy in Clinical Practice.

Prescribing the right medication, at the right dose, to the right patient is the goal of every physician. Pharmacogenomic information is an emerging tool that can be used to deliver precision medicine. In this review, we discuss the pharmacogenomics of available PPIs, racial differences of CYP2C19 and how PPI pharmacogenomics affects the treatment of common gastrointestinal diseases. We also provide practical guidance on when to order pharmacogenomic testing, which test to order, and how to modify treatment based on published guidelines.

Pharmacist Impact on Tacrolimus Serum Concentrations in Liver Transplant Patients.

Objective The purpose of this quality-improvement project was to determine if a pharmacist consultation following a liver transplant is associated with an increased percentage of drug levels in range after the patient sees the pharmacist. Setting Tertiary care, multispecialty medical clinic, and hospital providing solid-organ transplant. Practice Description Pharmacist consult service in a tertiary care, multispecialty medical clinic and hospital providing solid-organ transplant. Practice InnovationProvision of liver post-transplant consultations, not required by the Centers for Medicare & Medicaid Services, that results in therapeutic drug level improvement. Main Outcome MeasureTacrolimus therapeutic drug levels in range. Results A 96% improvement in quantity of therapeutic tacrolimus levels was seen in liver post-transplant patients after pharmacist post-transplant consultation. Results revealed 59 out of 74 (79.7%) post-liver transplant patients, 25 to 77 years of age (average 59.7 years), had an increased number of therapeutic tacrolimus levels after pharmacist post-transplant consultation. ConclusionWithout a pharmacist consultation following a liver transplant, patients may have a higher number of tacrolimus levels out of therapeutic range, placing them at increased risk for possible graft loss from low tacrolimus levels or toxicity resulting from high tacrolimus levels. Improvement in therapeutic tacrolimus levels after liver transplant was observed after patients received consultation and education from a clinical pharmacist. This finding creates an opportunity for pharmacists to implement services for patients after liver transplants to improve therapeutic tacrolimus levels.

Incorporation of Herbal Supplements into a Pharmacogenomic Medication Therapy Management Practice.

Personalized medicine, including direct-to-consumer (DTC) testing, is becoming a more common patient-centered approach to pharmacotherapy. However, DTC testing companies may not provide adequate information and follow-up to patients after genetic testing is done. This article is the first report describing a medication therapy management pharmacotherapy service that specializes in pharmacogenomic counseling, specifically geared toward identifying implications of dietary and herbal supplements. A pharmacist provides a comprehensive review of pharmacokinetic and pharmacodynamic consequences of a patient's herbal substances, and counseling is provided on subsequent drug therapy effects. If properly implemented, offering a pharmacogenomic medication therapy management service that specializes in the use of herbal supplements provides patients with education on the safe use of these substances based on their genetic factors.

Possible Parkinson's Disease Induced by Chronic Manganese Supplement Ingestion.

OBJECTIVE: The objective is to report a case of possible neurotoxicity resulting from an incorrect dietary supplement for osteoporosis taken at a toxic dose. SUMMARY: The case study examined here is a 37-year-old African-American female who consumed excessive manganese over a period of years, resulting in Parkinson's disease (PD). This patient was referred to the pharmacist pharmacotherapy service by a neurology physician. PD has been shown in the medical literature to be caused by chronic exposure to high levels of manganese. It may be concluded that daily doses of manganese well above the upper limit of 9 mg per day were taken by this patient for an extended period of time, possibly causing PD via manganism. CONCLUSION: This case illustrates the unknown risks taken by patients who use excessive amounts of over-the-counter herbals and supplements and how pharmacists can assist patients and physicians in the proper use of these popular products. ABBREVIATIONS: AI = Adequate intake, EMS = Eosinophilia myalgia syndrome, MTM = Medication therapy management, UL = Tolerable upper limit.

Creation of a Bariatric Surgery Medication Therapy Management Model.

OBJECTIVE: To describe how pharmacist-provided medication therapy management (MTM) services can be applied to bariatric surgery. PRACTICE SETTING: A pharmacy MTM consult service located in a multispecialty medical clinic with a bariatric department attached to a hospital where bariatric surgeries are performed. PRACTICE DESCRIPTION: MTM bariatric surgery office practice where patients are seen before surgery by a pharmacist to identify medication problems and determine how best to administer alternative dosage forms post-operatively to patients. PRACTICE INNOVATION: Practice innovations are a creation of a specialized service and accompanying specialized medication database within a pharmacotherapy practice. MAIN OUTCOME MEASURES: Outcome measures are number of patients referred per month and polypharmacy consults scheduled downstream from the bariatric surgery. Improved patient outcomes and prescribing efficiency from usage of the newly developed database of drugs that can be crushed. RESULTS: All bariatric patients are now referred to the pharmacist MTM pharmacotherapy service for medication review before bariatric surgery. CONCLUSION: Bariatric surgery is a source of another useful MTM practice model. Utilizing MTM pharmacists to consult with bariatric patients presurgery helps ease the physician burden of writing alternative dose prescriptions and helps identify medication problems with patients before their surgery.

An Analysis and Comparison of Medication Therapy Management Cost-Avoidance vs. Fee-for-Service Financial Models.

OBJECTIVE: To describe, compare, and contrast cost-avoidance and fee-for-service medication therapy management (MTM) financial models of practice to allow clinicians to better choose the type of MTM practice that best fits their particular practice environment. DATA SOURCES: Literature regarding pharmacist practices providing MTM services and capstone projects of proposed and currently operating MTM pharmacist practices presented in the University of Florida Master of Science MTM program. STUDY AND SOURCE SELECTION: Understanding the two major payment methods of sustaining a financially viable MTM pharmacist practice is critical to practice success. Survey was broad with regard to clinical models to compare differences because funding to support these services can be difficult to obtain. DATA SYNTHESIS: Despite differences in approach, various methods exist to financially sustain a pharmacist with an MTM practice. Each method or model has advantages and disadvantages in differing practice environments. CONCLUSION: With enough cost avoidance or revenue generation, financially dissimilar MTM financial models can be sustainable.

Polypharmacy as Formal Training and a Model of Practice.

Traditional definitions of polypharmacy may largely not account for the market proliferation of herbal and dietary supplements, cannabis products, or incorporate the new science of pharmacogenomics (PGx). Polypharmacy is encountered by most pharmacists providing patient care in many settings. The "polypharmacist" can assist patients and providers with solving medication-related problems (MRPs) in this new and challenging environment of supplements and cannabis products by utilizing traditional pharmacology and pharmacokinetic principles, including PGx, broadly across many medical disciplines. One may encounter polypharmacy more in the geriatric population, though in an age of supplements and cannabis proliferation, polypharmacy is increasingly being encountered at younger ages. Not only is polypharmacy training at best fragmented in pharmacy curricula, but it may also not account for the above-mentioned products that may use the same metabolic pathways to increase drug interactions and adverse drug reactions (ADRs) regarding prescription medications. Polypharmacy being more formally prioritized in pharmacist training may better prepare pharmacists for commonly encountered polypharmacy and can be a viable model of practice.

High-Evidence, Actionable Phenotype Gene Distribution in a Multispecialty, Tertiary Care Clinic: Potentially Actionable Genes and a Referring Department Profile.

Background There has been a trend in recent years toward individualized medicine. Pharmacogenomics (PGx) is the use of patient-specific genetic variations to guide medication selection and treatment. Objective: The primary objective was to characterize the population of referring department patients and identify the number of high-evidence, actionable phenotype (HEAP) genes in this referred population to help guide marketing efforts to the most applicable patient populations and departments. Practice description: Located in a destination, tertiary care clinic. Providers refer patients to a Pharmacogenomics (PGx) specialist for a comprehensive medication review using their pharmacogenomic results. Practice Innovation: The practice is innovative because it has been using PGx in the pharmacy and medical practices since 2016 and has been routinely developing and incorporating PGx best practice alerts (BPAs) into the electronic medical record (EMR) since 2020. Evaluation Methods Genetic results were analyzed from a 27-gene PGx panel test which tests for both pharmacokinetic and pharmacodynamic genes. High-Evidence Actionable Phenotypes (HEAP) are defined as phenotypes with guideline support that may suggest an action by healthcare provider. Low-Evidence Nonactionable Phenotypes (LENP) are defined as phenotypes that do not recommend action. Results There were 1,236 atypical phenotypes identified in the 154 patients referred. Of the atypical genes, 39.97% were HEAP and 60.03% were LENP. Of the HEAP's identified, the majority came from CYP2D6, VKORC1, and UGT1A1. At least 1 HEAP was found in 98.7% of patients (n=152). Conclusion There are a variety of High Evidence Actionable Phenotypes (HEAPs) with a high likelihood of at least one HEAP gene in every patient. These phenotypes can result in serious safety concerns when combined with a medication impacted by one of these HEAP genes. Thus, referral to a pharmacogenomics consultation service may lead to an overall decrease in morbidity and mortality with potential cost avoidance.

New Pneumococcal Vaccines for Prevention of Invasive Pneumococcal Disease in Adult Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at a high risk of developing invasive pneumococcal infection both before and after they are diagnosed. The Advisory Committee on Immunization Practices now endorses use of 2 new pneumococcal conjugate vaccines, PCV15 (Vaxneuvance) and PCV20 (Prevnar 20), for patients who have never received a pneumococcal conjugate vaccine or those with unknown vaccination history. Previous studies have shown that pneumococcal vaccination can decrease the risk of developing severe pneumococcal disease; therefore, it is important that patients with IBD receive pneumococcal vaccination. This report aims to inform clinicians who care for patients with IBD about the changes in immunization practices, as it pertains to pneumococcal vaccination and provides appropriate direction on administering vaccination series.

Two new pneumococcal vaccines (PCV15 [Vaxneuvance], PCV20 [Prevnar 20]) are now recommended for patients who have not received a pneumococcal conjugate vaccine or those with unknown vaccination history. This report summarizes changes in immunization practices and provides direction on vaccination series for patients with inflammatory bowel disease.

Should Business Training Be a Significant Element of Pharmacy Training?

Because pharmacists cannot be reimbursed for their clinical services and are not listed as providers under the US Social Security Act, they often have difficulty finding ways to financially support their services. Specifically, because pharmacists are not listed as providers, there is not usually sufficient financial support through reimbursement to cover pharmacist labor costs. Further, pharmacists must show that they save more in labor costs through cost avoidance to be accessible to patients in particular health care settings. Business training may provide a foundation for pharmacists to create financially viable models of practice and allow for better communication with administrative decision-makers, thus increasing the accessibility of their clinical services.

Chronic Serotonin Toxicity in the Older Patient With Polypharmacy.

Clinical pharmacists with experience may identify prescribing patterns resulting in iatrogenic disease, which is commonly encountered in geriatric populations where polypharmacy is common. Serotonin toxicity is one toxidrome clinicians may identify, where specific medications are used in treatment. As a result of their pharmacology training, pharmacists may identify toxidromes caused by medications that other clinicians may overlook. Pharmacogenomic (PGx) testing can provide added insight into a potentially iatrogenic cause for serotonin toxicity, because testing can elucidate how well an individual patient may metabolize serotonergic medications. Using PGx as a resource in addition to clinical experience, pharmacists can better guide therapy in the geriatric, polypharmacy population to avoid serotonin toxicity.

Phenytoin Toxicity with High Dose, Concomitant Ascorbic Acid Dosing.

High dose ascorbic acid may increase risk of phenytoin toxicity. This case report demonstrates high phenytoin levels resulting in adverse drug reactions subsequent to dosing concomitantly with high dose vitamin C, or ascorbic acid (AA), as a precaution against acquiring corona virus (COVID) infection. This patient suffered from a major seizure when he ran out of his phenytoin prescription. Subsequent initiation of phenytoin and later addition of high dose AA resulted in truncal ataxia and falls with bilateral wrist and finger extension weakness. Phenytoin and AA were discontinued, and the patient returned to baseline on a new medication regimen of lacosamide and gabapentin without any other major seizures one year later.

Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient.

Background: Pharmacogenomics (PGx) can provide more precision in determining causation of adverse drug reactions (ADRs) from drug-drug-gene interaction clinical application. Case Summary: Patient was an intermediate CYP2C19 metabolizer on stable therapy taking a low but therapeutic dose of sertraline for depression and anxiety over a period of 20 years. The patient then became hyponatremic and cognitively impaired after addition of cannabidiol (CBD) to this sertraline regimen. The proposed mechanism was drug-drug-gene interaction of CBD further inhibiting the CYP2C19 metabolism of sertraline and increasing drug exposure to produce moderate to severe hyponatremia and subsequent cognitive dysfunction. Practice Implications: Pharmacogenomics (PGx) testing may assist in etiology of patient symptoms from adverse drug reactions (ADRs) or drug-drug interactions by combining these with detection and application of drug-gene interactions. This case shows inhibition of CYP2C19 by CBD to further increase sertraline exposure, producing hyponatremia and subsequent cognitive dysfunction through CYP2C19 phenoconversion by CBD.

Conversion Disorder in a Pharmacogenomics, Polypharmacy Patient: Case Report.

Background: Conversion disorder (CD) is a relatively common psychiatric disorder likely encountered by clinical pharmacists but probably not easily identified by pharmacists. Case Summary: This is a patient case where a patient with a tremor was referred to the pharmacist led, polypharmacy, pharmacogenomics (PGx) service to rule out a PGx cause due to medication metabolism. No pharmacologic or PGx cause was found for the tremor which helped support and confirm a diagnosis of CD. Practice Implications: By working collaboratively with psychiatrists, neurologists, physical medicine colleagues, clinical pharmacists may add value to patient care by assisting with diagnoses and appropriate treatment.

Chronic Anticholinergic Toxicity Discovered in a Pharmacogenomics, Polypharmacy Patient.

OBJECTIVE: To report a case of chronic anticholinergic toxicity in a referred, pharmacogenomics (PGx), polypharmacy patient. SUMMARY: The patient is a 67-year-old male who was referred to the polypharmacy service for a PGx consult. This patient has had episodic fever of unknown origin, general cutaneous vasodilation, tremors, jerks, and brain fogginess which have been unexplained. He has seen specialists from infectious disease, rheumatology, endocrinology, and neurology with no contributory condition causing these symptoms, so he was referred for PGx testing and evaluation by the polypharmacy pharmacist. CONCLUSION: This case demonstrates the importance of pharmacist-patient consultations and how a PGx consult may expose polypharmacy medicationrelated problems of greater significance than the PGx indication for the consult. In addition, the case demonstrates positive interprofessional collaboration between pharmacists and physicians to more effectively solve complex medication-related problems that may not be easily diagnosed through objective lab or diagnostic testing.

Pharmacogenomics Testing Confirmation of Carbamazepine Induced DRESS Reaction of an HLA-A*31:01 Positive, Polypharmacy Patient.

Pharmacogenomics (PGx) melds well with polypharmacy as another tool to identify medication related problems (MRPs) more specifically so they may be solved most effectively. PGx can pre-emptively assist in medication selection, medication dosing or identify better medications for patients already taking a medication. PGx can also confirm suspect medications of causing MRPs such as adverse drug reactions (ADRs) or drug interactions. In this case, PGx testing confirmed presence of a serious human leukocyte antigen (HLA) drug reaction with eosinophilia and systemic symptoms (DRESS) after a suspect medication had been stopped.

Tacrolimus Therapeutic Drug Monitoring in Kidney Transplant Patients Before and After Pharmacist Post-transplant Consults.

Objectives: This quality improvement project sought to determine if clinical pharmacist office visits, or consults, had an impact on therapeutic tacrolimus levels in patients after kidney transplant through analysis of tacrolimus serum concentrations before versus after a pharmacist visit. Methods: A retrospective chart review was conducted for all patients that attended a clinical pharmacist office visit, also known as a consult, after kidney transplantation for a four month period. Pharmacists during the post-transplant consult reviewed adherence but also educated patients in detail about timing and logging of tacrolimus dosing, dosing with regard to labs to assure trough dosing, dosing with or without food in the stomach, what to do with a dose is taken late or if a dose is missed and foods, herbal supplements to avoid that may inhibit CYP3A4 to elevate tacrolimus levels. Results: After the post-transplant visit with a clinical pharmacist there was a 46% increase in the number of tacrolimus trough levels in therapeutic range versus before the pharmacist visit. Sixty-four percent of kidney transplant patients experienced an increase in the number of therapeutic drug levels in range after the pharmacist visit versus before the pharmacist visit. Conclusions: An increase in the quantity of therapeutic tacrolimus trough levels and the number of patients with therapeutic drug levels in range was observed after patients received pharmacist provided medication education post-transplant with emphasis on proper immunosuppressant medication administration, adherence and potential drug and food interactions. This finding demonstrates the importance of pharmacist clinical services in producing improved therapeutic drug levels in post-transplant kidney patients.

Tacrolimus-Induced Bradykinesia Secondary to Phenoconversion in an Elderly Post-Bilateral Lung Transplant Patient.

OBJECTIVE: To report pharmacogenomics post-related bradykinesia secondary to phenoconversion in an elderly post-bilateral lung transplant patient.SUMMARY: The patient was a 68-year-old double lung transplant patient taking the immunosuppressant and CYP3A4/5 substrate tacrolimus concomitantly with 2 CYP3A4/5 inhibitor medications, fluconazole and diltiazem. This drug combination post-dosing resulted in debilitating bradykinesia 1-2 hours after dosing, increasing the risk of falls and possible increased mortality and morbidity risk.CONCLUSION: Taking tacrolimus in combination with CYP3A4/5 inhibitors may increase neurologic adverse effects resulting in increased fall and associated increased mortality and morbidity risk.

Implications of Cannabidiol in Pharmacogenomic-Based Drug Interactions with CYP2C19 Substrates.

This is a patient case exploring the importance of evaluating herbal and dietary supplements and how they may impact drug-drug and drug-gene implications based on pharmacogenomics test results. Even though herbal supplements are considered natural by many patients, which is often the reason for starting them, herbal supplements may still be metabolized by the same pathways as other medications, potentially contributing to drug-drug, drug-herb, and drug-gene interactions, and therefore, potentially impacting a patient's response to medications.