Pharmacogenomics: Improving the Dynamic of Care in Medication Management 1

Current Issues in Medication Management and Pharmacogenomics Brief Biology & Pharmacogenomics Overview Drug Metabolism Clinical Implementation and physician adoption of Pharmacogenomics Main Topics 2

Current Issues in LTC New CMS Five Star Ratings Antipsychotic drugs - 693,000 residents revealed that 32.2% lacked appropriate indications for use 28.5% of the doses received were excessive Adverse Drug Reactions (ADR’s): Over 350,000/yr in nursing homes alone Unnecessary Medications - 27% of residents take 9 or more medications Institute of Medicine, National Academy Press, 2000; Lazarou J et al. JAMA 1998;279(15):1200–1205: Gurwitz JH et al. Am J Med 2000;109(2):87–94 3

Issues Elderly Populations Drug treatments may be unpleasant, painful, and life-threatening Drug Metabolism A patient may need twice the standard dose to be effective A drug works for one patient but not another One patient has side-effects and another doesn’t Drugs Ineffective drugs cost $billions/year 4

Medication-related Problems Falls, dizziness, impaired coordination GI bleeding Headaches, muscle pain, generalized aching/pain Rash, pruritus Seizure activity Spontaneous or unexplained bleeding, bruising Unexplained decline in functional status Urinary retention or incontinence 5

High Cost of Adverse Drug Reactions (ADRs) ADR’s are 4 th leading cause of in death in the US 5 th leading cause of illness 2.2 million hospitalizations per year 28% of hospitalized patients have ADRs Cost of drug related morbidity & mortality = $177 billion 6

Cost of ADR’s in Long Term Care Average hospital cost: $1,939 to $2,595 per ADR Total additional hospital cost: $3 - $4 billion Nursing facilities cost due to ADRs: $7.6 billion Medicare spends $3.5 billion on ADR’s in hospital setting and they account for 2-8% of readmissions 7

Quick Tour of You and Your DNA 46 Chromosomes 3 billion base pairs 100,000 genes capture full human variant Less than 10,000 may be pharmacologically relevant 8

Genes Over 20,000 genes (which encode proteins) 99.9% shared by humans, only 0.1% different 9

SNP’s (“SNIPS”) and DNA Variation SNP’s are a variation in the DNA sequence when a single nucleotide (A, T, C, or G) differs in individuals These DNA variations can affect how humans develop diseases and how they respond to medications 10

Past Approach to Medication Management What if Wilt is a poor metabolizer and Bill is an ultrarapid metabolizer of another pain med? “Adults: take 2 aspirin” Pharmacogenomics is a stronger determinant of efficacy than dosing factors such as age, weight and gender 11

New Definition of Medication Management using Pharmacogenomics “Products and Services that leverage genomics (directly or indirectly) to enable individualized approaches to care, and to choose the right medication at the right dose at the right time” 12

Personalized Medication Management 13

Pharmacogenomics seeks to predict what response an individual will have to a drug Human drug metabolism is largely an inherited trait Pharmacogenomics: “The study of how Genes affect a person’s response to medication” 14

Genes and Drug Metabolism Variations in genes that code for proteins can lead to poor response and ADR’s Cytochrome P450 genes encode enzymes that influence the metabolism of 70-80% of current prescription drugs Common examples are pain meds and antipsychotics, (CYP2D6), Warfarin (CYP2C9 & VKORC1), and Plavix (CYP2C19) 15

Examples of known medication issues Plavix – 19% of Americans are poor metabolizers. The FDA has added warning to Plavix label and recommends genetic testing Warfarin – very narrow therapeutic range; 20% of patients are hospitalized for bleeding within 6 months of starting. Research shows roughly 60% of patients should be prescribed a non- standard dose. Oncology: several drugs have known lethal toxicities and Pharmacogenomic testing is required before administering 16

Interpreting Reports - Genotype and Phenotype Genotypes are the letters of the DNA, or the Genes inside you. You cannot SEE Genotype. Phenotypes are the physical characteristics that you have - you can SEE Phenotype. 17

Drug Response by Phenotype 18

Example: Codeine Metabolism & 2D6 2D6 Phenotype Frequency in population: 19

Codeine Metabolism and Response - Active Drug (Warfarin) takes effect immediately -Prodrug (Codeine) becomes active after metabolism -Poor Metabolizers of Codeine get little or no response 20

Majority of Drugs are Ineffective 21

Individualized Medication Management 22

Pharmacogenomics (PGx) Guided Treatment 23

Variables involved in Personalized Medication Management 24

Physician attitudes towards adoption of PGx 25

26 PGx Test Result Interpretation - Example Reading a Pharmacogenomics Test Report

Current Medications and “Guidance Levels” 27

Current Meds and Guidance Levels (cont) 28

Potentially Impacted Medications and Drug Appendix 29

Physician Report on quality of life improvement: Resident discontinued Risperidone. Zyprexa initiated 2.5mg. Remeron was increased to 15mg. “Behaviors improved and not as many listless days” PGx changes = “red flag” antipsychotic with possible toxic side effects stopped; new antipsychotic (Zyprexa) added; dosage of antidepressant with no warnings increased I n response to PGx test results for this resident, action (in the form of medication changes) was taken in which outcomes improved PGx Case Study Follow-up 30

Benefits of Pharmacogenomics End to Trial and Error - Enables doctors to prescribe the “right dose of the right medicine at the right time” Increase the effectiveness of patient’s medication Reduce or eliminate drug toxicity or treatment failures Decrease adverse drug events (ADR’s) Decrease the total number of drugs taken by an individual 31