Copyright PGXL Laboratories, Louisville KY All materials herein are the exclusive property of PGXL Laboratories PGXL Panels August 2013 Kristen K. Reynolds, PhD VP Laboratory Operations

Single gene orders and ABN annotation Single req form for all medical specialties Panels revised based on ABN and common orders Physician information on top

Key Service Lines Pain Management – opioid resistance and opioid toxicity Behavioral Health – Drug selection to manage treatment resistant depression and psychosis – Dosing information to minimize adverse drug reactions Anti-platelet therapy – Clopidogrel resistance and increased bleeding risk Thrombotic risk assessment Statin therapy (ABN) – Minimum effective statin dose and myopathy risk Anti-coagulant therapy (ABN) – warfarin dose estimation and optimal INR interpretation guidance

Single Genes 2D6 2C19 MTHFR FII FV 3A4* 3A5* 1A2* 2C9* VKORC1* OPRM1* SLC6A4* SULT4A1* SLCO1B1* All genes orderable individually *requires ABN

Pain Management

Opioid Sensitivity 2D6 AddOPRM1* AddSLC6A4* Comprehensive Pain 2D6, 2C19, 2C9*, OPRM1* AddSLC6A4* *requires ABN

Opioid prodrug efficacy/ADR: 2D6 Active opioid dose: OPRM1* NSAID ADR: 2C9* Other opioids and muscle relaxers: 2C19, 3A4*/3A5*, 1A2* Methadone: 2C19 (active portion) Applications in Pain

Cardiology

Cardiovascular Health Warfarin 2C9*, VKORC1* Clopidogrel 2C19 Arrhythmia/Hypertension 2D6 Comprehensive CV Panel 2D6, 2C19, 2C9*, VKORC1* Thrombophilia Panel FII, FV, MTHFR *requires ABN

CV panels have no statin tests? All current statin tests require ABN 3A4, 3A5, 2C9, SLCO1B1 All orderable as single genes at the top of the req form

Clopidogrel guidelines update 2013 Deepening the evidence base Updated literature review New section on CYP2C19 sequencing and novel variants. This includes the novel *4B misclassification issue PGXL addresses in our recent abstract accepted to AMP New section on novel candidate genes. New section on who could be considered for CYP2C19 genotyping. Re-focus recommendations on patients with acute coronary syndromes undergoing PCI. Updated data linking CYP2C19 genotype to phenotype. Still no recommendations to increase dose in IMs. Discussion about how doubling the dose is not always enough in IMs and may need to be higher than 150mg/day, but no complete data for that yet Scott et al 2013

Behavioral health

Behavioral Health Basic Psychiatry Panel 2D6, 2C19 AddSLC6A4* AddSULT4A1* AddMTHFR STA 2 R Panel 2D6, 2C19, 2C9*, 3A4*, 3A5*, 1A2*, SULT4A1*, SLC6A4*, MTHFR *requires ABN

Basic Psychiatry Panel 2D6 and 2C19 account for many of the most common antidepressants and antipsychotics AddSLC6A4*SSRI sensitivity/resistance AddSULT4A1*olanzapine efficacy AddMTHFRL-methyl folate supplementation *requires ABN

Suregene Panel = 9 genes, 6 of which require ABN Available as full panel or single genes

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