Chronic Pain Management in a CYP2D6 Poor Metabolizer: A Case Report for Oxycodone.

The objective of this case report is to illustrate pharmacogenomics (PGx)-guided oxycodone treatment, given the conflicting data on the analgesic response from oxycodone in Cytochrome P450 (CYP)2D6 poor metabolizers (PMs). PGx-guided therapy can help improve treatment outcomes. This case report describes a 58-year-old patient who was prescribed oxycodone for chronic pain management. The patient presented with a history of inadequate pain control despite analgesic treatment with oxycodone (morphine milliequivalent [MME] = 22.5). Pharmacogenetic testing revealed that the patient was a CYP2D6 Poor Metabolizer (PM), which may shed light on the observed lack of analgesic response to oxycodone. The clinical pharmacist recommended switching to an alternative opioid not metabolized via the CYP2D6 pathway. The patient was subsequently switched to hydromorphone (MME = 16), resulting in improved pain control and fewer side effects. The newer hydromorphone dose accounted for a 30% MME dose reduction. The patient's initial average and worst pain score were 7 and 9 out of 10, respectively, per the numeric rating scale (NRS). Upon follow-up with the patient in two weeks, her average and worst pain scores improved to 3 and 3.5 out of 10, respectively, per the NRS. Further PGx testing results led to an overall positive outcome, such as her willingness to participate in physical therapy as a result of improved pain scores. This case highlights the importance of considering individual variability in drug metabolism when prescribing medications, particularly opioids such as oxycodone, to ensure optimal therapeutic outcomes and minimize the risk of adverse events in CYP2D6 PMs.

Utilizing Pharmacogenomics Results to Guide Antidepressant Selection: A Case Report.

The case discussion demonstrates the benefit of using Pharmacogenomic (PGx) results to aid in the selection of antidepressant therapy and improve response to treatment. Nearly half of patients diagnosed with major depressive disorder fail initial therapy and may require multiple trials of antidepressants. Genetic variation in several metabolic enzymes contribute to the variable response to antidepressant therapy. PGx testing provides an opportunity to inform antidepressant selection and optimize therapeutic outcomes, while minimizing risk of adverse events. A 79-year-old female who had been experiencing a suboptimal response to escitalopram following dose escalation over a period of three years was referred for a PGx consultation. A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions, and relevant clinical information to recommend alternative antidepressant therapy, which resulted in mood improvement.

Utilizing Pharmacogenomics Results to Improve Statin-Associated Muscle Symptoms.

The objective of this aims to demonstrate the advantage of a pharmacogenomics (PGx)-informed medication review in mitigating adverse drug events (ADEs) and optimizing therapeutic outcomes. PGx testing and PGx-informed medication reviews assist in mitigating ADEs. PGx testing was performed on a 68-year-old male presenting with uncontrolled chronic pain. The PGx results highlighted a drug-gene interaction, aiding in identification of the increased risk of statin-associated muscle symptoms (SAMS) attributing to uncontrolled chronic pain. This patient case report illustrates how incorporating PGx results can help improve chronic pain and mitigate ADEs, such as SAMS.

Pharmacogenetic Testing in a 70-Year-Old Woman with Polypharmacy and Multiple Comorbidities: A Case Report.

BACKGROUND Comorbidities and polypharmacy are difficult to manage, as polypharmacy hinders identification and prevention of medication-related problems. Risk for adverse drug events (ADEs) can be minimized through pharmacogenomic (PGx) testing and related therapeutic adjustments. CASE REPORT A 70-year-old woman with comorbidities and medications enrolled in the Program of All-inclusive Care for the Elderly presented with left lower extremity (LLE) pain, generalized weakness, and major depressive disorder. The provider requested a medication safety review, where the clinical pharmacist-recommended PGx testing given the LLE pain and weakness while taking a statin and inconsistent INR readings taking warfarin. The pharmacist recommended switching atorvastatin to pravastatin to minimize the risk for statin-associated ADEs due to CYP3A4 inhibition and switching fluoxetine to citalopram due to uncontrolled depression/anxiety and to mitigate drug-drug interactions with carvedilol to reduce the risk of orthostatic hypotension. Recommendations were accepted and upon follow-up the patient reported minor LLE pain and improved wellbeing on citalopram. Following PGx testing, the patient had decreased function at SLCO1B1 and was an intermediate metabolizer for CYP2C9 and CYP2D6. This case demonstrates how preemptive PGx testing would have identified drug-gene interactions (DGIs) at the time of prescribing and reduced the risk of statin-associated muscular symptoms, highlighting the utility of panel-based PGx testing in older adults at high risk for ADEs and/or therapy failure. CONCLUSIONS Decreased function at SLCO1B1 increases exposure to statins, leading to statin-induced myalgias, as displayed in this case. PGx testing can help identify DGIs, choose optimal therapies in medically complex older adults, and minimize ADE risk.

Pharmacogenomics and Drug-Induced Phenoconversion Informed Medication Safety Review in the Management of Pain Control and Quality of Life: A Case Report.

Utilizing pharmacogenomics (PGx) and integrating drug-induced phenoconversion to guide opioid therapies could improve the treatment response and decrease the occurrence of adverse drug events. Genetics contribute to the interindividual differences in opioid response. The purpose of this case report highlights the impact of a PGx-informed medication safety review, assisted by a clinical decision support system, in mitigating the drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively) that increase the risk of an inadequate drug response and adverse drug events (ADEs). This case describes a 69-year-old female who was referred for PGx testing for uncontrolled chronic pain caused by osteoarthritis and neuropathy. The clinical pharmacist reviewed the PGx test results and medication regimen and identified several (DGIs and DDGIs, respectively) at Cytochrome P450 (CYP) 2C19 and CYP2D6. The recommendations were to: (1) switch tramadol to buprenorphine transdermal patch, an opioid with lower potential for ADEs, to mitigate a CYP2D6 DDGI; (2) gradually discontinue amitriptyline to alleviate the risk of anticholinergic side effects, ADEs, and multiple DDGIs; and (3) optimize the pregabalin. The provider and the patient agreed to implement these recommendations. Upon follow-up one month later, the patient reported an improved quality of life and pain control. Following the amitriptyline taper, the patient experienced tremors in the upper and lower extremities. When the perpetrator drug, omeprazole, was stopped, the metabolic capacity was no longer impeded; the patient experienced possible amitriptyline withdrawal symptoms due to the rapid withdrawal of amitriptyline, which was reinitiated and tapered off more slowly. This case report demonstrates a successful PGx-informed medication safety review that considered drug-induced phenoconversion and mitigated the risks of pharmacotherapy failure, ADEs, and opioid misuse.

Emerging Non-statin Treatment Options for Lowering Low-Density Lipoprotein Cholesterol.

Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for the development of atherosclerotic cardiovascular disease. Statins have been the gold standard for managing cholesterol levels and reducing the risks associated with atherosclerotic cardiovascular disease; however, many patients do not achieve their cholesterol goals or are unable to tolerate this drug class due to adverse drug events. Recent studies of non-statin cholesterol lowering drugs (i.e., ezetimibe, PCSK9 inhibitors) have demonstrated cardiovascular benefits; and new drugs [i.e., bempedoic acid (BDA), inclisiran] have produced promising results in pre-clinical and clinical outcome trials. This narrative review aims to discuss the place in therapy of ezetimibe, PCSK9 inhibitors, BDA, and inclisiran and describe their relative pharmacokinetic (PK) profiles, efficacy and safety as monotherapy and combination therapy, and cardiovascular benefit(s) when used for hypercholesterolemia.

Medication-related problems encountered in the Program of All-Inclusive Care for the Elderly: An observational study.

OBJECTIVE: To evaluate pharmacist-encountered medication-related problems (MRPs) among the participants of the Program of All-Inclusive Care for the Elderly (PACE). DESIGN: This was a retrospective analysis of proprietary pharmacy records detailing pharmacist encounters with PACE clinical staff. SETTING AND PARTICIPANTS: A national provider of pharmacy services to more than 75 PACE organizations. In total, 1057 PACE participants at 69 PACE sites across the United States with documented pharmacist encounters between March and May 2018. OUTCOME MEASURES: MRPs were classified using the Hepler-Strand taxonomy, and pharmacists' recommendations made to prescribers to resolve these MRPs were classified using a modified Hoth taxonomy. In addition, pharmacists' communication methods and prescribers' responses were analyzed. RESULTS: Overall, 2004 MRPs were encountered. The most frequent MRPs identified were related to medication safety concerns, including drug interactions (720, 35.9%), adverse drug reactions (ADRs, 356, 17.8%), high doses (270, 13.5%), and unindicated drugs (252, 12.6%). Drug interactions frequently involved competitive inhibition, 3 or more drugs, opioids, anticoagulants, antiplatelets, and antidepressants. Deprescribe medication (561, 24.8%), start alternative therapy (553, 24.4%), change doses (457, 20.2%), and monitor (243, 10.7%) were the top 4 types of recommendations made by pharmacists. Among 1730 responses obtained from PACE prescribers, 78.1% (n = 1351) of pharmacists' recommendations were accepted. Compared with electronic communication, telephonic communication was associated with more acceptance and less prescriber nonresponse (χ2 = 78.5, P < 0.001). CONCLUSION: Pharmacists identified a substantial number of MRPs in PACE, especially those related to medication safety such as drug interactions and ADRs. In this practice setting, significant collaboration occured between pharmacists and PACE prescribers, as evidenced by the rate of prescribers' acceptance of pharmacists' recommendations. Further research is needed to fully evaluate the economic, clinical, and humanistic outcomes associated with pharmacists' encounters in PACE.