1. P HARMACOGENOMICS : P ERSONALIZING D RUG T HERAPY AT I NDIANA U NIVERSITY H EALTH Brian Decker MD, PharmD, MS Janet S. Carpenter, PhD, RN, FAAN Jennifer L. Milata, MSN, RN, ACNS-BC

2. OBJECTIVES 1. Describe a new Personalized Medicine initiative at IU Health 2. Discuss why personalized medicine is important to patient care 3. Discuss nursing considerations related to the new Personalized Medicine initiative at IU Health

3. N EW P ERSONALIZED M EDICINE I NITIATIVE AT IUH For a growing list of medications, a patient’s pharmacogenotype determines drug response and adverse drug effects. IU Health subspecialty medicine clinics will be able to determine the pharmacogenotypes of clinic patients. The long-term goal is to make pharmacogenotyping routine care at IUH clinics

4. W HAT IS P HARMACOGENOTYPING ? Simple blood draw Results identify variations in human genes regulating drug disposition, especially drug-metabolizing enzymes Variations can alter a person’s ability to metabolize certain drugs Different therapeutic responses to drugs Adverse drug events

5. W HAT ARE G ENETIC V ARIATIONS ? Most common type of genetic variation is a single nucleotide polymorphism (SNP or “snip”) See figure: Cytosine (C) changes to thymine (T) which changes the base pairs from cytosine and guanine (CG) to thymine and adenine (TA) SNPs alter a person’s ability to metabolize certain drugs

6. T HE P ERSONALIZED M EDICINE IN ITATIVE T ARGET D RUG L IST Amitryptyline Aripiprazole Atazanavir Atomoxetine Azathioprine Capcitabine Citalopram Clopidogrel Codeine Doxepin Efavirenz Escitalopram Esomeprazole Ezetimibe/simvastatin 5-Fluorouracil Glyburide Lansoprazole Mercaptopurine Nortriptyline Omeprazole Pantoprazole Phenytoin Rasburicase Simvastatin Tacrolimus Thioguanine Tramadol Venlafaxine Voriconazole Warfarin

7. IUH P ERSONALIZED M EDICINE C LINIC W ORK - FLOW Patients will be identified when prescribed 1 of the 38 target drugs for the first time Computer “pop- up” will alert the clinician of the availability of pharmacogenetic testing for this medication Pharmaco- genotyping test done Medical Record Automatic Consult Follow Morbidity, Mortality, Quality, Cost Data collected and analyzed for patient morbidity, mortality, quality and cost

8. NURSING CONSIDERATIONS Consent Patients must consent to pharmacogenotyping; Consent will be obtained by research nurses Patient Education Explain why a dosing adjustment or drug change was made Medications Be alert to and verify atypical drug doses; Regularly monitor and report adverse effects; Know the Personalized Medicine Target Drug list. Documentation Clarify and verify drug doses; Document patient education efforts; Document response to medications.

9. CASE STUDY Mrs. Jones was seen in an IU Health outpatient clinic and consented for pharmacogenotyping. Results show a SNP in her CYP2D6 drug metabolizing enzymes. She is a poor metabolizer of CYP2D6 drugs such as codeine, tramadol, dextromethorphan, fluoxetine, paroxetine, venlafaxine, and citalopram. These drugs should be avoided because they are not well metabolized.

10. Mrs. Jones asks why her codeine was stopped and another medication was started. Which is the best response? A.Your pharmacogenotyping blood test showed that codeine was not likely to be effective for you. B.Your pharmacogenotyping blood test showed that you were allergic to codeine. C.Your pharmacogenotyping blood test showed that you were likely to have a lot of side effects from the codeine. CASE STUDY CONT.

11. CASE STUDY: C ORRECT R ESPONSE A: Your pharmacogenotyping blood test showed that codeine was not likely to be effective for you. This answer is correct. Codeine is metabolized by the CYP2D6 enzyme to morphine. Because she cannot metabolize codeine well, she will not get effective pain relief.

12. CASE STUDY: I NCORRECT R ESPONSES B: Your pharmacogenotyping blood test showed that you were allergic to codeine. Being unable to metabolize a drug is not the same as being allergic to a medication. C: Your pharmacogenotyping blood test showed that you were likely to have a lot of side effects from the codeine. Because the drug is poorly metabolized, minimal side effects would be expected. If pharmacogenotyping had shown Mrs. Jones was an ultra-rapid metabolizer, she would be at greater risk for side effects from codeine.

13. S UMMARY Personalized Medicine at IU Health is a new initiative. Pharmacogenotyping results will be used to personalize medications to optimize drug efficacy and minimize side effects. Nurses need to be aware of personalized medication selection and dosing adjustments that may result from pharmacogenotyping Improved Patient Outcomes