Bangalore Call Girls Marathahalli 📞 9907093804 High Profile Service 100% Safe
Slides-Penner pharmacogenomic.pdf
1. PHARMACOGENOMICS
AN INTRODUCTION TO PERSONALIZED MEDICINE
Megan Penner-Willis, PharmD
Clinical Assistant Professor
UAA/ISU Doctor of Pharmacy Program
2. DISCLOSURES
I do not have (nor does any immediate family member have)
a vested interest in or affiliation with any corporate
organization offering financial support or grant monies for
this continuing education activity, or any affiliation with an
organization whose philosophy could potentially bias my
presentation.
3. LEARNING OBJECTIVES
Pharmacists &Technicians
• Define pharmacogenomics
• Recognize and problem solve barriers to pharmacogenomic testing
PharmacyTechnicians
• Identify potential role in
administering pharmacogenomic
tests
Pharmacists
• Identify patients who may benefit
from pharmacogenomic testing
5. 1. Exploring the use of Pharmacogenomic Testing in Primary Care for the Treatment of Depression and Anxiety | Mcubed. (n.d.). Retrieved January 5, 2020, from https://mcubed.umich.edu/projects/exploring-use-pharmacogenomic-testing-improve-depression-treatment-primary-care
6. THE MEDICATIONS
Over 200 medications have pharmacogenomic data listed in
the package insert
Over 10% of medications in the top 200 drug list
reference pharmacogenomics in the package insert
Over 20 different medication classes: analgesia, cardiology,
HIV, oncology, psychiatry
7. THE ENZYMES
Pharmacogenomics Testing. (n.d.). Retrieved September 6, 2018, from http://www.tarnowcenter.com/integrative-psychiatry/29-tarnow-articles/integrative-psychiatry/433-pharmacogenomics-testing.html
many
more
G6PD
Cytochrome
P450
9. THE ENZYMES - METABOLISM
Pharmacogenomics Testing. (n.d.). Retrieved September 6, 2018, from http://www.tarnowcenter.com/integrative-psychiatry/29-tarnow-articles/integrative-psychiatry/433-pharmacogenomics-testing.html
Ultra-rapid
Metabolizer
Low [Drug]
Extensive
Metabolizer
Normal [Drug]
Intermediate
Metabolizer
Variable [Drug]
Poor
Metabolizer
High [Drug]
Inactive Drug
Drug
10. Clopidogrel Active
Drug
2C19
If a person is a 2C19 poor metabolizer, what would be the predicted
impact on clopidogrel concentrations?
a) Increase
b) Decrease
c) No change
12. CLINICAL IMPACT
“Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic
Stroke or Transient Ischemic Attack”
• Up to 30% of the Caucasian population and 60% of the Eastern Asian
population has loss of CYP2C19 function alleles (*2, *3, *8)
• Statistically significant increased risk of stroke (12% vs 5.8%) and vascular
events (composite stroke, myocardial infarction, or vascular death: 13.7% vs
9.4%).
1. Pan Y, Chen W, Xu Y, Yi X, Han Y, Yang Q, Li X, Huang L, Johnston SC, Zhao X, Liu L, Zhang Q, Wang G, Wang Y, Wang Y. Genetic polymorphisms and clopidogrel efficacy for acute ischemic stroke or transient ischemic attack: a systematic review and meta-
analysis.Circulation. 2017;135:21–33. doi: 10.1161/CIRCULATIONAHA.116.024913.
2. Simon, T., & Danchin, N. (2017). Clinical Impact of Pharmacogenomics of Clopidogrel in Stroke. Circulation, 135(1), 34-37. doi:10.1161/circulationaha.116.025198
15. SSRI’S – HOPE FOR LESS TRIAL AND
ERROR?
• A cohort study of 1202 patients suggests sertraline dose
reductions of 60% and 25% in poor metabolizers and
intermediate metabolizers, respectively (Braten et al.,
2019).
• Additional studies provide dosing recommendations for
citalopram, escitalopram, fluvoxamine, and paroxetine
based on pharmacogenomic testing.
1. Bråten, L.S., Haslemo, T., Jukic, M.M. et al. Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients. Neuropsychopharmacol. (2019) doi:10.1038/s41386-019-0554-x
2. 1. Kaye, A. D., Garcia, A. J., Hall, O. M., Jeha, G. M., Cramer, K. D., Granier, A. L., … Urman, R. D. (2019). Update on the pharmacogenomics of pain management. Pharmacogenomics and personalized medicine, 12, 125–143. doi:10.2147/PGPM.S179152
16. GUIDED TRIAL
• Largest-ever pharmacogenomics-guided depression trial
• 1167 patients with major depressive disorder with at least
one previously failed depression medication
• Significant improvement in remission (15% vs 10%,
p=0.007) and response rates (26% vs 20%, p=0.013)with
pharmacogenomic-guided care versus standard care
1. Greden, J. F., Parikh, S. V., Rothschild, A. J., Thase, M. E., Dunlop, B. W., DeBattista, C., … Dechairo, B. (2019). Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study. Journal of
Psychiatric Research, 111, 59–67. https://doi.org/10.1016/j.jpsychires.2019.01.003
17. COST SAVINGS IN MENTAL HEALTH
TREATMENT
1. The Pharmacist’s Value in Pharmacogenetic Testing for Mental Health. (n.d.). Retrieved January 5, 2020, from Pharmacy Times website: https://www.pharmacytimes.com/publications/issue/2019/august2019/the-pharmacists-value-in-pharmacogenetic-testing-for-mental-health
18. PAIN MANAGEMENT
• Codeine: contraindicated in children <12 years due to risk
of respiratory depression from ultra-rapid metabolization
via CYP2D6
• Tramadol: prodrug also activated by CYP2D6
1. Kaye, A. D., Garcia, A. J., Hall, O. M., Jeha, G. M., Cramer, K. D., Granier, A. L., … Urman, R. D. (2019). Update on the pharmacogenomics of pain management. Pharmacogenomics and personalized medicine, 12, 125–143. doi:10.2147/PGPM.S179152
19. PAIN MANAGEMENT
• Fentanyl: no statistically significant findings for
polymorphism-related adverse events
• Hydrocodone: metabolized to hydromorphone via
CYP2D6
• Morphine: studies have demonstrated relationship between
polymorphisms and pain control, respiratory depression
1. Kaye, A. D., Garcia, A. J., Hall, O. M., Jeha, G. M., Cramer, K. D., Granier, A. L., … Urman, R. D. (2019). Update on the pharmacogenomics of pain management. Pharmacogenomics and personalized medicine, 12, 125–143. doi:10.2147/PGPM.S179152
20. CARDIOVASCULAR
• A randomized, open-label study of 2488 patients found in
patients undergoing PCI, a CYP2C19 genotype-guided
strategy for antiplatelet therapy was noninferior with
regards to thrombotic events and resulted in lower
incidence of bleeding (Claassens et al., 2019).
• There is evidence to support cost effectiveness of PGX
testing for clopidogrel and warfarin, but evidence is lacking
for other areas of cardiovascular care (Zhu et al., 2019).
1. Claassens, D. M. F., Vos, G. J. A., Bergmeijer, T. O., Hermanides, R. S., van ’t Hof, A. W. J., van der Harst, P., … ten Berg, J. M. (2019). A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. New England Journal of Medicine, 381(17), 1621–1631.
https://doi.org/10.1056/NEJMoa1907096
2. Zhu, Y., Swanson, K.M., Rojas, R.L. et al. Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases. Genet Med (2019) doi:10.1038/s41436-019-0667-y
22. PHARMACOGENOMIC
TESTING
Cheek swab
One time cost of
$150-400
1. The Utility of Pre-emptive Pharmacogenomic Testing. (n.d.). Retrieved January 5, 2020, from RxGenomix website:
https://www.rxgenomix.com/insight/the-utility-of-pre-emptive-pharmacogenomic-testing/
24. LIMITATIONS
FDA Stance:“The FDA is alerting patients and health care providers that
claims for many genetic tests to predict a patient's response to specific
medications have not been reviewed by the FDA, and may not have the
scientific or clinical evidence to support this use for most medications.
Changing drug treatment based on the results from such a genetic test
could lead to inappropriate treatment decisions and potentially serious
health consequences for the patient.”
1. US Food and Drug Administration. The FDA Warns Against the Use of Many Genetic Tests With Unapproved Claims to Predict Patient Response to Specific Medications. https://www.fda.gov/medical-devices/safety-communications/fda-warns-against-use-many-genetic-tests-unapproved-
claims-predict-patient-response-specific. Accessed December 30, 2019.
25. FDA APPROVAL
• “Direct-to-consumer”
• Requires statement that consumers should not use test
results to stop or change medications
• FDA approval = test is accurate and reproducible
29. PHARMACOGENOMICS IN PRACTICE
Obtain Sample
Educate Patient
and Provider on
Results
(if still admitted)
Adjust
Medications
(if still admitted)
Inpatient
30. THE UNIVERSITY OF
CHICAGO CENTER FOR
PERSONALIZED MEDICINE
Genomic Prescribing System
(GPS)
The University of Chicago Center for Personalized Therapeutics. (n.d.). Retrieved August 2, 2018, from https://cpt.uchicago.edu/
31. COVERAGE & REIMBURSEMENT
• October 2019 – United Healthcare started covering PGX
testing for patients diagnosed with anxiety and depression
whose medication(s) has failed
• Medicare can cover pharmacogenomic testing if deemed
medically necessary…
• Individual PGX suppliers provide reimbursement for
providing PGX education and consultation
1. Pharmacogenetic Testing. (2019). Retrieved from https://www.uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/pharmacogenetic-testing.pdf
33. APPLYING TO PRACTICE
What area of pharmacogenomics interests you or
would be most applicable to your practice site?
34. RESEARCH TO WATCH
• MillionVeteran Program
• RIGHT 10K Study
• 1200 Patients Project
35. TRAINING & CERTIFICATE PROGRAMS
• American Society of Health-System Pharmacists
(ASHP)
• National Association of Chain Drug Stores
(NACDS) – Test2Learn
• University of Colorado
37. PHARMACOGENOMICS
AN INTRODUCTION TO PERSONALIZED MEDICINE
Megan Penner-Willis, PharmD
Clinical Assistant Professor
UAA/ISU Doctor of Pharmacy Program
pennmeg2@isu.edu
