In a recent article by Bill Kubat, LNHA – Move over patient-centered care, make way for precision medicine, Manju Beier explains how pharmacogenetics fills a need in LTC.
Several terms, including “precision medicine,” “stratified medicine,” “targeted medicine,” “pharmacogenetics” and “pharmacogenomics” are sometimes used interchangeably with “personalized medicine.” The American Medical Association describes personalized medicine as “health care that is informed by each person’s clinical, genetic and environmental information.”
Pharmacogenetics Fills a Need
To better understand its implications in long-term care, I visited with Manju T. Beier, PharmD, CGP. Dr. Beier is president and founder of Geriatric Consultant Resources, LLC, a firm that provides clinical expertise in pharmacotherapy and clinical pharmacology to geriatrics professional organizations, managed care organizations, and health care plans. Dr. Beier has been a frequent presenter at AMDA – the Society for Post-Acute and Long-Term Care Medicine conferences.
Dr. Beier explained that the recognition of PGx as a science with clear implications for patient-centered care has been facilitated by the convergence of several factors across all health care, including implications for long-term care:
•The need for improved therapeutics. Studies and numbers frequently cited by the FDA and other regulators include a 2001 study that showed that the response rates of patients to medications from different therapeutic classes ranged from about 80% for analgesics to about 25% for oncology, 52% for osteoporosis, 75% for cancer chemotherapy, 70% for Alzheimer’s disease, 38% for depression, 43% for diabetes, 50% for arthritis, 48% for migraine (prophylaxis), 40% for asthma, and 40% for cardiac arrhythmias. Varying response rates to medications may be explained by a variety of factors; perhaps underlying variability in pharmacogenetics is one of them.
• Increased focus on adverse drug reactions. An estimated 2.2 million adverse drug reactions occur each year in the United States, including more than 100,000 deaths. Older adults with polypharmacy are especially at risk.
• Increased emphasis on medication management. PGx is potentially useful for predicting dosing, toxic side effects, and therapeutic effects, and for eliciting drug-gene interactions.
• Effects on measurable outcomes. Clinical studies evaluating the impact of pharmacogenetic-guided dosing and monitoring on ED visits, hospitalizations, quality of life, and health care costs are few and far between but slowly making their way into the literature.
To move it from the hypothetical to the concrete, consider the following case as described by Dr. Beier in The Consultant Pharmacist (Beier MT. Pharmacogenetics: has the time come for pharmacists to embrace and implement the science? Consult Pharm 2013;11:696–711):
~ Mr. J is an 83-year-old patient who resides independently in a senior living community. His past medical history includes depression comorbid with dementia, hypertension, and type 2 diabetes. He has no known allergies to medications. He has taken several anti-depressants in the recent past, including amitriptyline, paroxetine, and citalopram for his major depressive disorder. However, he either failed to achieve an adequate response or exhibited intolerable side effects to these medications. His current daily medications include simvastatin 20 mg, glipizide 5 mg, sertraline 50 mg, donepezil 5 mg, aspirin 81 mg, lisinopril-hydrochlorothiazide 20 to 25 mg, and metformin 500 mg twice daily. At the request of the consultant pharmacist, and in light of his past history with medication intolerance for depression, the physician orders cytochrome P450 genetic testing.
The resident’s pharmacogenetic results indicate that he is an ultra-rapid metabolizer of the CYP2C19 pathway and could potentially need higher doses of sertraline, which is metabolized via CYP2C19. CYP2D6 is a minor pathway in the metabolism of sertraline, and the resident’s poor metabolizer status suggests the need for extra vigilance. Based on the consultant pharmacist’s recommendation, the physician increases the sertraline dose gradually while monitoring for response over the next several weeks.
Eventually, the patient achieves a significant reduction in symptoms at a dose of 150 mg/day. The ultra-rapid CYP2C19 status may explain why the patient previously did not respond to citalopram, also a CYP2C19 substrate. The citalopram dose was not increased beyond 20 mg daily, complying with FDA-recommended maximum dose limits set for citalopram in the elderly. Amitriptyline is converted to nortriptyline via CYP2C19, and both amitriptyline and nortriptyline are further metabolized via the CYP2D6 pathway. As an ultra-rapid metabolizer of CYP2C19 and a poor metabolizer of CYP2D6, the resident may have had increased levels of nortriptyline, potentially causing his intolerance to the medication.
Similarly, his intolerance to paroxetine may have been as a result of his poor CYP2D6 status. It is well recognized that older patients, especially with dementia, are more susceptible to the anticholinergic side effects from nortriptyline and amitriptyline. This, combined with a poor metabolizer status, could potentially increase the risk for adverse events from paroxetine as well, which exhibits some antimuscarinic activity and has recently been added to the Beers list as a generally inappropriate medication to use in the elderly. Changes were not made to donepezil, as he was clinically stable at the prescribed dose.
This case illustrates how pharmacogenetic testing and appropriate resultant interventions can enable a patient to be maintained in the environment they wish to call home. It also illustrates the need for collaboration across the inter- disciplinary team with patient assessment (note the involvement of the consultant pharmacist) to identify the appropriateness of testing and determining interventions based on those test results.
PGx Medical is the trusted and experienced resource for the implementation of pharmacogenetics in the field of aging services. For more information on pharmacogenetics or to schedule a speaker/educator, contact: PGx Medical, info@pgxmed.com, 405-509-5112.
Read entire article at: caringfortheages.com