Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

PATIENT INFORMATION SAMPLE REFERRING PHYSICIAN Name: Test, Matthew Date Collected: April 16, 2018 Name: Gregory House, MD DOB: November 1, 1960 Date Received: May 4, 2018 Institution: ADHD Plus Inc Age: 57 Case ID: PGPSL18-000001 Address: 1046 Central Parkway South Sex: Male Source: Buccal Swabs San Antonio, TX 78232 Address: 123 Main Street Phone: (910)123-4567 Suite 1000 COPY TO: Marcus Welby, M.D. Any Town, Any State 12345 Address: 1 Any Street Any Town, NJ 12345 Phone: 555-456-5768

Comprehensive Drug Information for Test, Matthew

NORMAL RESPONSE EXPECTED PROCEED WITH CAUTION

Drug Impacted Drug Impacted Clinical Interpretation

ADHD: CNS STIMULANTS

$PSKHWDPLQH $GGHUDOOŠ 'H[WURDPSKHWDPLQH $GGHUDOOŠ Due to increased severity of social 'H[PHWK\OSKHQLGDWH )RFDOLQŠ 0HWK\OSKHQLGDWH 5LWDOLQŠ withdrawal or nausea /LVGH[DPIHWDPLQH 9\YDQVHŠ 0HWKDPSKHWDPLQH 'HVR[\QŠ

ADHD: SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS) $WRPR[HWLQH 6WUDWWHUDŠ REPORT

ALCOHOLISM: ALDEHYDE DEHYDROGENASE INHIBITORS

'LVXOILUDP $QWDEXVHŠ

ANTIANXIETY

%XVSLURQH %XVSDUŠ

ANTIANXIETY: BENZODIAZEPINES $OSUD]RODP ;DQD[Š SAMPLE'LD]HSDP 9DOLXPŠ Due to possible increased ADRs /RUD]HSDP $WLYDQŠ 0LGD]RODP 9HUVHGŠ 2[D]HSDP 6HUD[Š

ANTIDEPRESSANTS: DOPAMINE/NOREPINEPHRINE-REUPTAKE INHIBITORS

%XSURSLRQ :HOOEXWULQŠ Due to reduced response and increased risk of side effects

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 1 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

NORMAL RESPONSE EXPECTED PROCEED WITH CAUTION

Drug Impacted Drug Impacted Clinical Interpretation

ANTIDEPRESSANTS: SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)

(VFLWDORSUDP /H[DSURŠ &LWDORSUDP &HOH[DŠ Due to reduced response 9LOD]RGRQH 9LLEU\GŠ )OXR[HWLQH 3UR]DFŠ Due to elevated risk for drug overdose 9RUWLR[HWLQH 7ULQWHOOL[Š resulting in adverse events and drug interaction

)OXYR[DPLQH /XYR[Š Due to reduced response 3DUR[HWLQH 3D[LOŠ 6HUWUDOLQH =RORIWŠ

ANTIDEPRESSANTS: SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS)

'XOR[HWLQH &\PEDOWDŠ 0LOQDFLSUDQ 6DYHOODŠ Due to reduced response /HYRPLOQDFLSUDQ )HW]LPDŠ 5HER[HWLQH (GURQD[Š

ANTIDEPRESSANTS: SEROTONIN REUPTAKE INHIBITORS/ANTAGONISTS

7UD]RGRQH 'HV\UHOŠ ANTIDEPRESSANTS: ALPHA-2 ANTAGONISTS REPORT 0LUWD]DSLQH 5HPHURQŠ Due to possible increased ADRs

ANTIPSYCHOTICS

$ULSLSUD]ROH $ELOLI\Š Chlorpromazine Due to possible increased QT interval %UH[SLSUD]ROH 5H[XOWLŠ Fluphenazine +DORSHULGRO +DOGROŠ &OR]DSLQH &OR]DULOŠ Due to increased risk of side effects ,ORSHULGRQH )DQDSWŠ including hyperprolactinemia and Perphenazine weight gain 3LPR]LGH 2UDSŠ SAMPLE2ODQ]DSLQH =\SUH[DŠ Due to increased risk of side effects 4XHWLDSLQH 6HURTXHOŠ

MOOD STABILIZER: ANTIMANIC AGENTS

&DUEDPD]HSLQH 7HJUHWROŠ /LWKLXP /LWKRELGŠ Due to possible less drug response /DPRWULJLQH /DPLFWDOŠ 9DOSURLF$FLG 'HSDNRWHŠ

OPIOID OVERDOSE: OPIOIDS ANTAGONISTS

1DOR[RQH (Y]LRŠ 1DOWUH[RQH 5HYLDŠ

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 2 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

NORMAL RESPONSE EXPECTED PROCEED WITH CAUTION

Drug Impacted Drug Impacted Clinical Interpretation

OTHER STIMULANTS

Cocaine Cannabinoids Due to increased risk of tetrahydrocannabinol (THC) dependence

REPORT

SAMPLE

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 3 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Table of Contents

I. Results Driven ICD -10 Diagnosis Code and Current Medication

II. Current Medication List

Clinical interpretation for patient’s current medications provided by physician Includes pharmacogenomics and drug interactions (drug-drug, drug-food, drug-alcohol, drug-lab)

III. Summary Psychiatric Drugs

A summary of commonly prescribed medications for psychiatric illnesses by drug class. Including drugs that go through multiple pathways and final recommendations

Color boxes: clinically significant pathway Gray box: clinically limited relevant pathwayREPORT

IV. Comprehensive Drug List

Includes clinical interpretation for a 53-gene panel and over 300 drugs, arranged by therapeutic area This section is designated to help optimize treatment options and manage patients with multiple conditions, effectively and efficiently SAMPLE Level of Evidence Legend

z FDA Actionable PGx – Package insert œ PharmGKB, CPIC, EMA, DPWG, PMDA, HCSC { Medical Literature

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 4 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

I. ICD-10 Diagnosis Code and Current Medication Driven Result for Test, Matthew ICD-10: F32.9 Major depressive disorder, single episode, unspecified;F41.9 Anxiety disorder, unspecified;F31.9 Bipolar disorder, unspecified Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Alpha-2 Antagonists: 0LUWD]DSLQH 5HPHURQŠ œ USE CAUTION CYP2D6 Intermediate Metabolizer *4/*10 1 due to possible increased ADRs 2 3 Anti-Anxiety Agents: %XVSLURQH %XVSDUŠ { NORMAL RESPONSE EXPECTED HTR1A rs6295 CC WT/WT genotype/rs1800044 C Allele 1 Carrier 2 3 Anticonvulsant Drugs: &ORED]DP 2QILŠ z NORMAL RESPONSE EXPECTED CYP2C19 Intermediate Metabolizer *1/*2 1 2 3 Anticonvulsant Drugs: 9DOSURLF$FLG 'HSDNRWHŠ œ NORMAL RESPONSEREPORT EXPECTED ANKK1 A1 Heterozygous WT/c.2137G>A 1 2 3 Antilipemic Agents (Statins): $WRUYDVWDWLQ /LSLWRUŠ œ USE CAUTION KIF6 rs20455 AA genotype WT/WT 3UDYDVWDWLQ 3UDYDFKROŠ œ due to poorer response to statin treatment with decreased risk for 1 adverse cardiovascular events 2 Antilipemic Agents (Statins):SAMPLE $WRUYDVWDWLQ /LSLWRUŠ œ USE CAUTION ABCB1 rs2032582 AA due to higher risk of developing WT/WT genotype/rs1045642 AA 1 genotype myalgia 2 3 Antilipemic Agents (Statins): /RYDVWDWLQ 0HYDFRUŠ œ NORMAL RESPONSE EXPECTED CYP3A5 Expresser *1A/*3A 5RVXYDVWDWLQ &UHVWRUŠ œ 1 2

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 5 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Antilipemic Agents (Statins): 3LWDYDVWDWLQ /LYDORŠ œ NORMAL RESPONSE EXPECTED SLCO1B1 Normal Activity *1/*1 5RVXYDVWDWLQ &UHVWRUŠ œ 1 2 Antimanic Agents: /LWKLXP /LWKRELGŠ œ USE CAUTION ABCB1 rs2032582 AA due to possible less drug response WT/WT genotype/rs1045642 AA 1 genotype 2 3 Antiplatelets: &ORSLGRJUHO 3ODYL[Š z CONSIDER ALTERNATIVES CYP2C19 Intermediate Metabolizer *1/*2 1 (if no contraindication e.g., prasugrel, ticagrelor) 2 3 4 Antipsychotics: 5LVSHULGRQH 5LVSHUGDOŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 1 (e.g., quetiapine, olanzapine, clozapine) 2 REPORT 3 4 Antipsychotics: 7KLRULGD]LQH 0HOODULOŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 1 2 3 4 Antipsychotics: SAMPLE Chlorpromazine œ USE CAUTION CYP1A2 Normal Metabolizer *1A/*1F Fluphenazine œ due to possible increased QT interval 1 2 Antipsychotics: &OR]DSLQH &OR]DULOŠ œ USE CAUTION ANKK1 A1 Heterozygous WT/c.2137G>A 1 due to increased risk of side effects including hyperprolactinemia and 2 weight gain 3

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 6 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Antipsychotics: &OR]DSLQH &OR]DULOŠ œ USE CAUTION HTR2C rs1414334 C Allele Carrier WT/WT 1 due to increased risk of developing metabolic syndrome 2 3 Antipsychotics: 2ODQ]DSLQH =\SUH[DŠ œ USE CAUTION SLC6A4 HTTLPR Long Form LA/LA 4XHWLDSLQH 6HURTXHOŠ œ due to increased risk of side effects 1 2 Antipsychotics: 2ODQ]DSLQH =\SUH[DŠ œ USE CAUTION ANKK1 A1 Heterozygous WT/c.2137G>A 1 due to increased risk of side effects including hyperprolactinemia and 2 weight gain 3 Antipsychotics: 2ODQ]DSLQH =\SUH[DŠ œ USE CAUTION HTR2C rs1414334 C Allele Carrier WT/WT 1 due to increased risk of developing metabolic syndrome 2 3 Antipsychotics: REPORT $ULSLSUD]ROH $ELOLI\Š z NORMAL RESPONSE EXPECTED CYP2D6 Intermediate Metabolizer *4/*10 %UH[SLSUD]ROH 5H[XOWLŠ z ,ORSHULGRQH )DQDSWŠ z 3LPR]LGH 2UDSŠ z Antipsychotics: $ULSLSUD]ROH $ELOLI\Š œ NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer *1A/*1B 1 2 3 SAMPLE Antipsychotics: +DORSHULGRO +DOGROŠ œ NORMAL RESPONSE EXPECTED CYP2D6 Intermediate Metabolizer *4/*10 1 2 3 Antipsychotics: Perphenazine z NORMAL RESPONSE EXPECTED CYP2D6 Intermediate Metabolizer *4/*10 1 2 3

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 7 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Benzodiazepines: 'LD]HSDP 9DOLXPŠ z USE CAUTION CYP2C19 Intermediate Metabolizer *1/*2 1 due to possible increased ADRs 2 3 Benzodiazepines: $OSUD]RODP ;DQD[Š { NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer *1A/*1B 1 2 3 Benzodiazepines: /RUD]HSDP $WLYDQŠ œ NORMAL RESPONSE EXPECTED UGT2B15 rs1902023 non-AA genotype *1/*2 2[D]HSDP 6HUD[Š œ 1 2 Benzodiazepines: 0LGD]RODP 9HUVHGŠ œ NORMAL RESPONSE EXPECTED CYP3A5 Expresser *1A/*3A 1 2 3 Dopamine/Norepinephrine-Reuptake Inhibitors: REPORT %XSURSLRQ :HOOEXWULQŠ œ USE CAUTION CYP2B6 G516T Homozygous/A785G due to reduced response and G516T/G516T/A78 Homozygous 1 5G/A785G increased risk of side effects 2 3 Dopamine/Norepinephrine-Reuptake Inhibitors: %XSURSLRQ :HOOEXWULQŠ œ USE CAUTION CYP2C19 Intermediate Metabolizer *1/*2 1 due to reduced response and increased risk of side effects 2 3 SAMPLE Opioids: 0HWKDGRQH 0HWKDGRVHŠ œ DECREASE DOSE CYP2B6 G516T Homozygous/A785G G516T/G516T/A78 Homozygous 1 5G/A785G 2 3 Opioids: %XSUHQRUSKLQH 6XEXWH[Š { DECREASE DOSE CYP3A4 Intermediate Metabolizer *1A/*1B )HQWDQ\O 'XUDJHVLFŠ { 6XIHQWDQLO 6XIHQWDŠ { OR 1 USE CAUTION due to the risk of increased exposure to the drug leading to adverse events

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 8 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Selective Serotonin Reuptake Inhibitors (SSRIs): &LWDORSUDP &HOH[DŠ œ USE CAUTION GRIK4 rs1954787 T Allele Carrier WT/WT 1 due to reduced response 2 3 Selective Serotonin Reuptake Inhibitors (SSRIs): )OXR[HWLQH 3UR]DFŠ z USE CAUTION CYP2D6 Intermediate Metabolizer *4/*10 1 due to elevated risk for drug overdose resulting in adverse events 2 and drug interaction 3 Selective Serotonin Reuptake Inhibitors (SSRIs): )OXYR[DPLQH /XYR[Š œ USE CAUTION HTR1A rs6295 CC due to reduced response WT/WT genotype/rs1800044 C Allele 3DUR[HWLQH 3D[LOŠ œ Carrier 6HUWUDOLQH =RORIWŠ œ 1 Selective Serotonin Reuptake Inhibitors (SSRIs): 6HUWUDOLQH =RORIWŠ œ USE CAUTION CYP2C19 Intermediate Metabolizer *1/*2 1 with high alert to adverse drug events 2 3 Selective Serotonin Reuptake Inhibitors (SSRIs): REPORT (VFLWDORSUDP /H[DSURŠ z NORMAL RESPONSE EXPECTED CYP2C19 Intermediate Metabolizer *1/*2 1 2 3 Selective Serotonin Reuptake Inhibitors (SSRIs): (VFLWDORSUDP /H[DSURŠ œ NORMAL RESPONSE EXPECTED SLC6A4 HTTLPR Long Form LA/LA 1 2 3 SAMPLE Selective Serotonin Reuptake Inhibitors (SSRIs): 9LOD]RGRQH 9LLEU\GŠ { NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer *1A/*1B 1 2 3 Selective Serotonin Reuptake Inhibitors (SSRIs): 9RUWLR[HWLQH 7ULQWHOOL[Š z NORMAL RESPONSE EXPECTED CYP2D6 Intermediate Metabolizer *4/*10 1 2 3

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 9 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 9HQODID[LQH (IIH[RUŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 1 (e.g., citalopram, sertraline) 2 3 4 Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 0LOQDFLSUDQ 6DYHOODŠ œ USE CAUTION ADRA2A rs1800544 GG due to reduced response WT/c.-217G>A genotype/rs1800545 GA 1 genotype 2 3 Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 0LOQDFLSUDQ 6DYHOODŠ œ USE CAUTION HTR1A rs6295 CC due to reduced response WT/WT genotype/rs1800044 C Allele 1 Carrier 2 3 Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 'XOR[HWLQH &\PEDOWDŠ { NORMAL RESPONSE EXPECTED CYP1A2 Normal Metabolizer *1A/*1F 1 2 REPORT 3 Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): Levomilnacipran { NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer )HW]LPDŠ *1A/*1B 1 2 3 Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 5HER[HWLQH (GURQD[Š { NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer *1A/*1B 1 SAMPLE 2 3 Serotonin Reuptake Inhibitors/Antagonists: 7UD]RGRQH 'HV\UHOŠ { NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer *1A/*1B 1 2 3 Tetracyclic Antidepressants: Maprotiline œ DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 1 2 3

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 10 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Tricyclic Antidepressants: $PLWULSW\OLQH (ODYLOŠ z DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 &ORPLSUDPLQH $QDIUDQLOŠ z by 25% 'R[HSLQ 6LOHQRUŠ z ,PLSUDPLQH 7RIUDQLOŠ z 3URWULSW\OLQH 9LYDFWLOŠ z 7ULPLSUDPLQH 6XUPRQWLOŠ z Tricyclic Antidepressants: 'HVLSUDPLQH 1RUSUDPLQŠ z DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 1RUWULSW\OLQH 3DPHORUŠ z by 25% 1 2 Vitamins: Folic Acid œ CONSIDER ALTERNATIVES MTHFR A1298C Heterozygous (e.g., supplements containing C677T/C677T/A12 Mutation/C677T 1 98C Homozygous Mutation methylfolate) due to significantly 2 reduced folic acid conversion 3 4 Disclaimer: The ICD-10 codes page may be left blank because ICDREPORT codes were not provided or not applicable.

SAMPLE

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 11 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

II. Current Medication List for Test, Matthew

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Antilipemic Agents (Statins): Lipitor œ USE CAUTION KIF6 rs20455 AA genotype due to poorer response to statin WT/WT treatment with decreased risk for adverse cardiovascular events Antilipemic Agents (Statins): Lipitor œ USE CAUTION ABCB1 rs2032582 AA due to higher risk of developing WT/WT genotype/rs1045642 AA genotype myalgia Antiplatelets: Plavix z CONSIDER ALTERNATIVES CYP2C19 Intermediate Metabolizer (if no contraindication e.g., prasugrel, *1/*2 ticagrelor) Benzodiazepines: Alprazolam { NORMAL RESPONSE EXPECTED CYP3A4 Intermediate Metabolizer *1A/*1B

Dopamine/Norepinephrine-Reuptake Inhibitors: Wellbutrin œ USE CAUTION CYP2B6 G516T Homozygous/A785G due to reduced responseREPORT and G516T/G516T/A78 Homozygous 5G/A785G increased risk of side effects

Dopamine/Norepinephrine-Reuptake Inhibitors: Wellbutrin œ USE CAUTION CYP2C19 Intermediate Metabolizer due to reduced response and *1/*2 increased risk of side effects Opioids: Methadone œ DECREASE DOSE CYP2B6 G516T Homozygous/A785G G516T/G516T/A78 Homozygous SAMPLE 5G/A785G Vitamins: Folic Acid œ CONSIDER ALTERNATIVES MTHFR A1298C Heterozygous (e.g., supplements containing C677T/C677T/A12 Mutation/C677T 98C Homozygous Mutation methylfolate) due to significantly reduced folic acid conversion Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Aspirin NA CLINICAL EVIDENCE NOT CYP2C19 Intermediate Metabolizer SUFFICIENT *1/*2

Antibiotics: Clindamycin NA CLINICAL INTERPRETATION NOT NA NA AVAILABLE

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 12 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Action Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Antipsychotics: Lurasidone NA PHARMACOGENOMICS NA NA EVIDENCE NOT AVAILABLE

REPORT

SAMPLE

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Drug-Drug Interactions for Test, Matthew

Severity Drugs Warning Documentation Clinical Management ASPIRIN -- MAJOR FAIR Concomitant use of aspirin with a platelet activation and CLOPIDOGREL Concurrent use of ASPIRIN and aggregation inhibitor, such as clopidogrel, may increase the ULVNRIEOHHGLQJ 3URG,QIR3/$9,;ŠRUDOWDEOHWV HYDROGEN CLOPIDOGREL may result in an increased risk of bleeding. 3URG,QIR$**5(12;ŠRUDOH[WHQGHGUHOHDVHFDSVXOHV SULFATE 2012). If coadministration is required, monitoring of blood counts may be warranted.

BUPROPION MAJOR FAIR Coadministration of buPROPion with a CYP2B6 inhibitor HYDROCHLORIDE Concurrent use of BUPROPION may increase exposure of buPROPion but decrease exposure of hydroxybupropion, an active metabolite of -- and SELECTED CYP2B6 INHIBITORS may result in buPROPion. If concurrent use is required, adjust the dose CLOPIDOGREL increased buPROPion exposure of buPROPion, based on clinical response (Prod Info HYDROGEN and decreased hydroxybupropion WELLBUTRIN SR oral sustained-release tablets, 2013; SULFATE exposure. Prod Info WELLBUTRIN oral tablets, 2013), and if concurrent use is required with buPROPion/naltrexone, do not exceed 2 tablets/day of the combination product (Prod ,QIR&2175$9(ŠRUDOH[WHQGHGUHOHDVHWDEOHWV  LURASIDONE MAJOR FAIR Patients receiving therapy with CNS depressants including HYDROCHLORIDE Concurrent use of LURASIDONE lurasidone should not be denied access to medication- assisted treatment (MAT) drugs (eg, methadone and -- and METHADONE may result in increased risk of respiratory and buprenorphine). Although the risk of serious side effects, METHADONE CNS depression. overdose, and death is increased with concomitant use, HYDROCHLORIDE withholding access to MAT may lead to greater risk of morbidity and mortality related to opioid use disorder. Discontinuation of the CNS depressant is preferred in most cases. If concomitant use is necessary, monitor and manage cautiously; consider tapering the CNS depressant to the lowest effective dose or using alternative options for REPORTthe treatment of anxiety or insomnia (US Food and Drug Administration (FDA), 2017). METHADONE MAJOR FAIR Reserve the concomitant use of methadone and CNS HYDROCHLORIDE Concurrent use of METHADONE depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the -- and CNS DEPRESSANTS may result in increased risk of respiratory lowest dose and shortest duration necessary to achieve ALPRAZOLAM and CNS depression. treatment goals. Consider using a lower dose of methadone or the CNS depressant and closely monitor for sedation and respiratory depression (Prod Info '2/23+,1(ŠRUDOWDEOHWV 3DWLHQWVUHFHLYLQJ therapy with benzodiazepines or other CNS depressants should not be denied access to medication-assisted treatment (MAT) drugs (eg, methadone and buprenorphine). Although the risk of serious side effects, overdose, and death is increased with concomitant use, SAMPLE withholding access to MAT may lead to greater risk of morbidity and mortality related to opioid use disorder. Discontinuation of the benzodiazepine or CNS depressant is preferred in most cases. If concomitant use is necessary, monitor and manage cautiously; consider tapering the benzodiazepine or CNS depressant to the lowest effective dose or using alternative options for the treatment of anxiety or insomnia (US Food and Drug Administration (FDA), 2017). ATORVASTATIN MODERATE EXCELLENT If a patient develops high on-treatment platelet reactivity CALCIUM -- Concurrent use of CLOPIDOGREL during treatment with clopidogrel and a statin metabolized by CYP3A4 (ie, atorvastatin, lovastatin, or simvastatin), CLOPIDOGREL and CYP3A4 METABOLIZED STATINS may result in decreased discontinue the statin and substitute a statin that is not HYDROGEN formation of clopidogrel active metabolized by CYP3A4 (ie, pravastatin or rosuvastatin) SULFATE metabolite resulting in high on- (Park et al, 2012). treatment platelet reactivity.

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 14 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Drug-Food Interactions for Test, Matthew

Severity Drugs Warning Documentation Clinical Management ALPRAZOLAM -- MAJOR GOOD Concurrent use of alprazolam with grapefruit juice may GRAPEFRUIT Concurrent use of ALPRAZOLAM increase alprazolam plasma concentrations (Prod Info ;$1$;ŠRUDOWDEOHWV (QFRXUDJHSDWLHQWVWRDYRLG JUICE and GRAPEFRUIT JUICE may result in increased alprazolam grapefruit juice consumption during alprazolam therapy. exposure.

CLOPIDOGREL MAJOR EXCELLENT Advise patients to avoid consuming grapefruit juice during HYDROGEN Concurrent use of CLOPIDOGREL clopidogrel therapy, as decreased plasma concentrations and reduced antiplatelet activity of the active clopidogrel SULFATE -- and GRAPEFRUIT JUICE may result in reduced exposure of the metabolite may result (Holmberg et al, 2013). GRAPEFRUIT active clopidogrel metabolite. JUICE

LURASIDONE MAJOR FAIR The concomitant use of lurasidone, a CYP3A4 substrate, HYDROCHLORIDE Concurrent use of LURASIDONE and grapefruit juice, a CYP3A4 inhibitor, should be avoided (Prod Info LATUDA(TM) oral tablets, 2013). -- and GRAPEFRUIT JUICE may result in increased lurasidone GRAPEFRUIT plasma concentrations. JUICE

ASPIRIN -- MODERATE FAIR Avoid concomitant use of celery with antiplatelet agents. If CELERY Concurrent use of ANTIPLATELET both are taken together monitor the patient closely for signs AGENTS and CELERY may result and symptoms of bleeding. in increased risk of bleeding. REPORT ATORVASTATIN MODERATE EXCELLENT The ingestion of large quantities of grapefruit juice, CALCIUM -- Concurrent use of ATORVASTATIN especially in excess of 1.2 liters per day, with atorvastatin can result in elevated atorvastatin plasma levels and an GRAPEFRUIT and GRAPEFRUIT JUICE may result in increased bioavailability of LQFUHDVHGULVNIRUP\RSDWK\ 3URG,QIR/,3,725ŠRUDO JUICE atorvastatin resulting in an tablets, 2009). Monitor for increased atorvastatin side increased risk of myopathy or effects. rhabdomyolysis. CLOPIDOGREL MODERATE FAIR Avoid concomitant use of celery with antiplatelet agents. If HYDROGEN Concurrent use of ANTIPLATELET both are taken together monitor the patient closely for signs and symptoms of bleeding. SULFATE -- AGENTS and CELERY may result in increased risk of bleeding. CELERY SAMPLE

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 15 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Drug-Alcohol Interactions for Test, Matthew

Severity Drugs Warning Documentation Clinical Management BUPROPION MAJOR GOOD Ingestion of ethanol should be minimized, and preferably HYDROCHLORIDE Concurrent use of BUPROPION avoided completely, in patients receiving buPROPion (Prod ,QIR:(//%875,1ŠRUDOWDEOHWV  -- and ETHANOL may result in an increased risk of seizures, ETHANOL neuropsychiatric events or reduced tolerance to alcohol.

ALPRAZOLAM -- MODERATE FAIR Patients receiving alprazolam should be advised against ETHANOL Concurrent use of ALPRAZOLAM ethanol use. and ETHANOL may result in increased sedation.

ASPIRIN -- MODERATE GOOD Concomitant use of alcohol and aspirin may increase the ETHANOL Concurrent use of ETHANOL and risk of gastrointestinal injury and bleeding and should be ASPIRIN may result in increased undertaken with caution. Chronic or heavy alcohol risk of gastrointestinal bleeding. consumption may increase this risk (Prod Info DuoCover oral film coated tablets, 2016). METHADONE MODERATE FAIR Patients receiving methadone should be advised against HYDROCHLORIDE Concurrent use of METHADONE ethanol use. -- and ETHANOL may result in increased sedation. ETHANOL REPORT

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Drug-Lab Interactions for Test, Matthew

Severity Drugs Warning Documentation Clinical Management BUPROPION MODERATE EXCELLENT The administration of buPROPion has resulted in a false- HYDROCHLORIDE BUPROPION may result in a false- positive urine amphetamine immunoassay results in some screening tests that lack specificity. More specific methods, -- positive urine amphetamine test result due to cross-reactivity due to such as a gas chromatographic-mass spectrometer AMPHETAMINE structural similarity of amphetamine technique, will be able to distinguish between buPROPion MEASUREMENT and buPROPion and its metabolites. and amphetamine (Prod Info Aplenzin oral film coated H[WHQGHGUHOHDVHWDEOHWV3URG,QIR:(//%875,1Š oral film-coated tablets, 2011; Prod Info WELLBUTRIN 65ŠRUDOVXVWDLQHGUHOHDVHWDEOHWV3URG,QIR :(//%875,1;/ŠRUDOH[WHQGHGUHOHDVHWDEOHWV 

Disclaimer: The Current Medication section may be left blank if no medication list provided. The Drug Interactions section may be left blank if no drug interactions were found for drugs on the current medication list or no medication list was provided.

REPORT

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III. Summary Psychiatric Drugs for Test, Matthew

Drugs by Drug Class ABCB1 ADRA2A ANKK1 CES1 CNR1 COMT CYP1A2 CYP2B6 CYP2C19 CYP2D6 CYP3A4 CYP3A5 DRD1 DRD2 FAAH GRIK4 HLA-B HTR1A HTR2A HTR2C OPRM1 SCN2A SLC6A4 UGT2B15 Final recommendation ALDEHYDE DEHYDROGENASE INHIBITORS 'LVXOILUDP $QWDEXVHŠ 8 ANTI-ANXIETY AGENTS $OSUD]RODP ;DQD[Š 8 %XVSLURQH %XVSDUŠ 8 'LD]HSDP 9DOLXPŠ 8 /RUD]HSDP $WLYDQŠ 8 0LGD]RODP 9HUVHGŠ 8 2[D]HSDP 6HUD[Š 8 3URSUDQRORO ,QGHUDO/$Š 8 ANTIDEPRESSANTS $PLWULSW\OLQH (ODYLOŠ 8 8 %XSURSLRQ :HOOEXWULQŠ 8 8 REPORT &LWDORSUDP &HOH[DŠ 8 8 8 8 &ORPLSUDPLQH $QDIUDQLOŠ 8 8 'HVLSUDPLQH 1RUSUDPLQŠ 8 'R[HSLQ 6LOHQRUŠ 8 8 'XOR[HWLQH &\PEDOWDŠ 8 (VFLWDORSUDP /H[DSURŠ 8 8 )OXR[HWLQH 3UR]DFŠ 8 )OXYR[DPLQH /XYR[Š 8 8 ,PLSUDPLQH 7RIUDQLOŠ 8 8 /HYRPLOQDFLSUDQ )HW]LPDŠ SAMPLE 8 Maprotiline 8 0LOQDFLSUDQ 6DYHOODŠ 8 8 0LUWD]DSLQH 5HPHURQŠ 8 1RUWULSW\OLQH 3DPHORUŠ 8 3DUR[HWLQH 3D[LOŠ 8 8 3URWULSW\OLQH 9LYDFWLOŠ 8 8 5HER[HWLQH (GURQD[Š 8 6HUWUDOLQH =RORIWŠ 8 8 7UD]RGRQH 'HV\UHOŠ 8 7ULPLSUDPLQH 6XUPRQWLOŠ 8 8 9HQODID[LQH (IIH[RUŠ 8 9LOD]RGRQH 9LLEU\GŠ 8 9RUWLR[HWLQH 7ULQWHOOL[Š 8

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Drugs by Drug Class ABCB1 ADRA2A ANKK1 CES1 CNR1 COMT CYP1A2 CYP2B6 CYP2C19 CYP2D6 CYP3A4 CYP3A5 DRD1 DRD2 FAAH GRIK4 HLA-B HTR1A HTR2A HTR2C OPRM1 SCN2A SLC6A4 UGT2B15 Final recommendation ANTIMANIC AGENTS /LWKLXP /LWKRELGŠ 8 ANTIPSYCHOTICS $ULSLSUD]ROH $ELOLI\Š 8 8 %UH[SLSUD]ROH 5H[XOWLŠ 8 Chlorpromazine 8 &OR]DSLQH &OR]DULOŠ 8 8 8 8 Fluphenazine 8 +DORSHULGRO +DOGROŠ 8 ,ORSHULGRQH )DQDSWŠ 8 2ODQ]DSLQH =\SUH[DŠ 8 8 8 8 Perphenazine 8 3LPR]LGH 2UDSŠ 8 4XHWLDSLQH 6HURTXHOŠ 8 8 5LVSHULGRQH 5LVSHUGDOŠ 8 8 8 8 8 7KLRULGD]LQH 0HOODULOŠ REPORT8 CNS STIMULANTS (ADHD) $PSKHWDPLQH $GGHUDOOŠ 8 8 $WRPR[HWLQH 6WUDWWHUDŠ 8 'H[PHWK\OSKHQLGDWH )RFDOLQŠ 8 'H[WURDPSKHWDPLQH $GGHUDOOŠ 8 8 /LVGH[DPIHWDPLQH 9\YDQVHŠ 8 0HWKDPSKHWDPLQH 'HVR[\QŠ 8 0HWK\OSKHQLGDWH 5LWDOLQŠ 8 8 8 MOOD STABILIZERS &DUEDPD]HSLQH 7HJUHWROŠ SAMPLE 8 8 /DPRWULJLQH /DPLFWDOŠ 8 9DOSURLF$FLG 'HSDNRWHŠ 8 OPIOIDS ANTAGONISTS 1DOR[RQH (Y]LRŠ 8 1DOWUH[RQH 5HYLDŠ 8 OTHER STIMULANTS Cannabinoids 8 Cocaine 8

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 19 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

IV. Comprehensive Drug List for Test, Matthew Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Anesthesiology General Anesthetics: .HWDPLQH .HWDODUŠ œ DECREASE DOSE CYP2B6 G516T G516T/G516T/A7 Homozygous/A785G 3URSRIRO 'LSULYDQŠ œ due to decreased drug clearance 85G/A785G Homozygous 2 3 Anesthesiology Local Anesthetics: /LGRFDLQH3ULORFDLQH (PODŠ z CONSIDER ALTERNATIVES G6PD G6PD Deficiency WT/Mediterranea 5 due to high susceptibility to drug- n induced methemoglobinemia 2 3 4 Anesthesiology Local Anesthetics: /LGRFDLQH /LGRGHUPŠ { NORMAL RESPONSE CYP1A2 Normal Metabolizer *1A/*1F 5RSLYDFDLQH 1DURSLQŠ { EXPECTED 2 3 Anesthesiology Sedatives: 'H[PHGHWRPLGLQH 3UHFHGH[Š œ NORMALREPORT RESPONSE ADRA2A rs1800544 GG EXPECTED WT/c.-217G>A genotype/rs1800545 GA 2 genotype 3 4 Cardiology ACE Inhibitors: &DSWRSULO &DSRWHQŠ œ USE CAUTION ACE ACE Deletion WT/WT 4XLQDSULO $FFXSULOŠ œ due to reduced response 2 3 Cardiology ACE Inhibitors: %HQD]HSULO /RWHQVLQŠ SAMPLEœ NORMAL RESPONSE ACE ACE Deletion WT/WT 3HULQGRSULO $FHRQŠ œ EXPECTED 2 3 Cardiology ACE Inhibitors: 3HULQGRSULO $FHRQŠ œ NORMAL RESPONSE AGTR1 rs5186 AA genotype WT/WT 2 EXPECTED 3 4 Cardiology Angiotensin II Receptor Blockers: ,UEHVDUWDQ $YDSURŠ œ USE CAUTION ACE ACE Deletion WT/WT 2 due to reduced response 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 20 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Cardiology Angiotensin II Receptor Blockers: /RVDUWDQ &R]DDUŠ œ USE CAUTION AGTR1 rs5186 AA genotype WT/WT 2 due to reduced response 3 4 Cardiology Angiotensin II Receptor Blockers: &DQGHVDUWDQ $WDFDQGŠ œ NORMAL RESPONSE AGTR1 rs5186 AA genotype WT/WT 2 EXPECTED 3 4 Cardiology Antianginal Drugs: 5DQROD]LQH 5DQH[DŠ œ NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Cardiology Antiarrhythmic Drugs: 3URSDIHQRQH 5\WKPROŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 5 (e.g., sotalol, disopyramide, quinidine, amiodarone) 2 3 4 REPORT Cardiology Antiarrhythmic Drugs: )OHFDLQLGH 7DPERFRUŠ œ DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 2 by 25% 3 4 Cardiology Antiarrhythmic Drugs: 'LJR[LQ /DQR[LQŠ œ USE CAUTION ABCB1 rs2032582 AA WT/WT genotype/rs1045642 AA 2 due to decreased metabolism genotype 3 4 SAMPLE Cardiology Antiarrhythmic Drugs: $PLRGDURQH &RUGDURQHŠ œ NORMAL RESPONSE NOS1AP rs10494366 GG EXPECTED WT/WT genotype/rs10800397 C 2 Allele 3 Carrier/rs10919035 C Allele Carrier 4 Cardiology Antiarrhythmic Drugs: 'URQHGDURQH 0XOWDTŠ œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 21 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Cardiology Anticoagulants: 3KHQSURFRXPRQ 0DUFRXPDUŠ œ NORMAL RESPONSE CYP4F2 Normal Metabolizer *1/*1 2 EXPECTED 3 4 Cardiology Anticoagulants: 5LYDUR[DEDQ ;DUHOWRŠ { NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Cardiology Anticoagulants: :DUIDULQ &RXPDGLQŠ z NORMAL DOSE CYP2C9 Normal Metabolizer *1/*1 2 Warfarin daily dose 5-7mg 3 4 Cardiology Anticoagulants: :DUIDULQ &RXPDGLQŠ z NORMAL DOSE VKORC1 rs9923231 A Allele WT/-1639G>A Carrier 2 Warfarin daily dose 5-7mg 3 4 Cardiology Antilipemic Agents: )HQRILEUDWH 7ULFRUŠ { NORMALREPORT RESPONSE APOB rs676210 AA Genotype EXPECTED c.8216C>T/c.821 2 6C>T 3 4 Cardiology Antilipemic Agents: )HQRILEUDWH 7ULFRUŠ œ NORMAL RESPONSE APOE Non E2 Carrier WT/WT 2 EXPECTED 3 4 Cardiology Antilipemic Agents (Statins): $WRUYDVWDWLQ /LSLWRUŠ SAMPLEœ USE CAUTION KIF6 rs20455 AA genotype WT/WT 3UDYDVWDWLQ 3UDYDFKROŠ œ due to poorer response to statin 2 treatment with decreased risk for adverse cardiovascular events 3 Cardiology Antilipemic Agents (Statins): $WRUYDVWDWLQ /LSLWRUŠ œ USE CAUTION ABCB1 rs2032582 AA WT/WT genotype/rs1045642 AA 2 due to higher risk of developing genotype 3 myalgia 4 Cardiology Antilipemic Agents (Statins): /RYDVWDWLQ 0HYDFRUŠ œ NORMAL RESPONSE CYP3A5 Expresser *1A/*3A 5RVXYDVWDWLQ &UHVWRUŠ œ EXPECTED 2 3

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Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Cardiology Antilipemic Agents (Statins): 3LWDYDVWDWLQ /LYDORŠ œ NORMAL RESPONSE SLCO1B1 Normal Activity *1/*1 5RVXYDVWDWLQ &UHVWRUŠ œ EXPECTED 2 3 Cardiology Antilipemic Agents (Statins): )OXYDVWDWLQ /HVFROŠ œ NORMAL RESPONSE ACE ACE Deletion WT/WT 2 EXPECTED 3 4 Cardiology Antilipemic Agents (Statins): /RYDVWDWLQ 0HYDFRUŠ { NORMAL RESPONSE LDLR rs688 TT Genotype EXPECTED c.1773C>T/c.177 2 3C>T 3 4 Cardiology Antilipemic Agents (Statins): 6LPYDVWDWLQ =RFRUŠ œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 2 genotype 3 4 Cardiology Antilipemic Agents (Statins): 6LPYDVWDWLQ =RFRUŠ œ NORMALREPORT RESPONSE SLCO1B1 Normal Activity *1/*1 2 EXPECTED 3 4 Cardiology Antiplatelets: &ORSLGRJUHO 3ODYL[Š z CONSIDER ALTERNATIVES CYP2C19 Intermediate Metabolizer *1/*2 5 (if no contraindication e.g., prasugrel, ticagrelor) 2 3 4 SAMPLE Cardiology Antiplatelets: 7LFDJUHORU %ULOLQWDŠ z NORMAL DOSE CYP2C19 Intermediate Metabolizer *1/*2 2 3 4

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Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Cardiology Beta Blockers: 0HWRSURORO /RSUHVVRUŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 5 (e.g., bisoprolol, carvedilol) 2 OR 3 4 DECREASE DOSE by 50% due to heart failure caused by the decreased drug cardioselectivity

Cardiology Beta Blockers: $WHQRORO 7HQRUPLQŠ œ USE CAUTION ADRA2A rs1800544 GG WT/c.-217G>A genotype/rs1800545 GA 2 due to decreased drug response genotype 3 4 Cardiology Beta Blockers: &DUYHGLORO &RUHJŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Cardiology Beta Blockers: REPORT 1HELYRORO %\VWROLFŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 3URSUDQRORO ,QGHUDO/$Š z EXPECTED 2 3 Cardiology Calcium Channel Blockers: $PORGLSLQH 1RUYDVFŠ œ USE CAUTION NOS1AP rs10494366 GG WT/WT genotype/rs10800397 C 1LIHGLSLQH $GDODWŠ { due to increased risk for QTc Allele 2 prolongation Carrier/rs10919035 C Allele Carrier 3 Cardiology Calcium Channel SAMPLEBlockers: 9HUDSDPLO &DODQŠ œ USE CAUTION NOS1AP rs10494366 GG WT/WT genotype/rs10800397 C 2 due to increased risk for QTc Allele 3 prolongation Carrier/rs10919035 C Allele Carrier 4 Cardiology Calcium Channel Blockers: 'LOWLD]HP &DUGL]HPŠ { NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B )HORGLSLQH 3OHQGLOŠ { EXPECTED /HUFDQLGLSLQH =DQLGLSŠ { 1LVROGLSLQH 6XODUŠ { Cardiology Calcium Channel Blockers: 1LWUHQGLSLQH 1LWUHSLQŠ œ NORMAL RESPONSE AGTR1 rs5186 AA genotype WT/WT 2 EXPECTED 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 24 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Cardiology Diuretics: %XPHWDQLGH %XPH[Š œ NORMAL RESPONSE ACE ACE Deletion WT/WT )XURVHPLGH /DVL[Š œ EXPECTED +\GURFKORURWKLD]LGH 0LFUR]LGHŠ œ 7RUVHPLGH 'HPDGH[Š œ Cardiology Diuretics: +\GURFKORURWKLD]LGH 0LFUR]LGHŠ œ NORMAL RESPONSE AGTR1 rs5186 AA genotype WT/WT 2 EXPECTED 3 4 Cardiology Diuretics: 6SLURQRODFWRQH $OGDFWRQHŠ œ NORMAL RESPONSE ACE ACE Deletion WT/WT 2 EXPECTED 3 4 Cardiology Miscellaneous Cardiovascular Agents: ,YDEUDGLQH &RUODQRUŠ œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Cardiology Phosphodiesterase Inhibitors: &LORVWD]RO 3OHWDOŠ œ NORMALREPORT RESPONSE CYP3A5 Expresser *1A/*3A 2 EXPECTED 3 4 Cardiology Vasodilators: Hydralazine z USE CAUTION NAT2 Rapid Acetylator *4/*12 2 due to decreased drug response 3 4 Cardiology Vasodilators: 1LWURSUXVVLGH 1LWURSUHVVŠ SAMPLEœ NORMAL RESPONSE ACE ACE Deletion WT/WT 2 EXPECTED 3 4 Dentistry Cholinergic Agonists: &HYLPHOLQH (YR[DFŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Endocrinology Biguanides: 0HWIRUPLQ *OXFRSKDJHŠ œ NORMAL RESPONSE ATM rs11212617 CC WT/WT genotype 2 EXPECTED 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 25 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Endocrinology Endocrine Enzyme Inhibitors: (OLJOXVWDW &HUGHOJDŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Endocrinology Sulfonylureas: &KORUSURSDPLGH 'LDELQHVHŠ z CONSIDER ALTERNATIVES G6PD G6PD Deficiency WT/Mediterranea *OLPHSLULGH $PDU\OŠ z n *OLSL]LGH *OXFRWUROŠ z *O\EXULGH *O\QDVHŠ z Tolbutamide { Endocrinology Thiazolidinediones: 3LRJOLWD]RQH $FWRVŠ œ NORMAL RESPONSE CYP2C8 Wild Type *1/*1 2 EXPECTED 3 4 Endocrinology Thiazolidinediones: 5RVLJOLWD]RQH $YDQGLDŠ œ NORMAL RESPONSE CYP2C8 Wild Type *1/*1 2 EXPECTED 3 4 Gastroenterology Histamine H2 Antagonists: REPORT )DPRWLGLQH 3HSFLGŠ { NORMAL DOSE CYP2C19 Intermediate Metabolizer *1/*2 2 3 4 Gastroenterology Monoclonal Antibody: $GDOLPXPDE +XPLUDŠ { NORMAL RESPONSE HFE rs2071303 C Allele WT/c.340+4T>C Carrier 2 EXPECTED 3 4 Gastroenterology Osmotic Laxatives:SAMPLE $VFRUELF$FLG 0RYL3UHSŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 2 due to a risk of hemolytic anemia n 3 4 Gastroenterology Proton Pump Inhibitors (PPIs): 'H[ODQVRSUD]ROH 'H[LODQWŠ z USE CAUTION CYP2C19 Intermediate Metabolizer *1/*2 (VRPHSUD]ROH 1H[LXPŠ z due to higher drug plasma levels /DQVRSUD]ROH 3UHYDFLGŠ z 2PHSUD]ROH 3ULORVHFŠ z 3DQWRSUD]ROH 3URWRQL[Š z 5DEHSUD]ROH $FLSKH[Š z

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 26 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Gynecology Hormonal Contraceptives: Ethinyl Estradiol/Norelgestromin z NORMAL RESPONSE F5 Non Factor V Leiden 2UWKR(YUDŠ EXPECTED WT/WT Carrier 2 3 4 Gynecology Hormones: Oral-Contraceptive œ NORMAL RESPONSE F2 Wild Type WT/WT 2 EXPECTED 3 4 Gynecology Mixed 5-HT1A Agonists/5-HT2A Antagonists: )OLEDQVHULQ $GG\LŠ z NORMAL RESPONSE CYP2C19 Intermediate Metabolizer *1/*2 2 EXPECTED 3 4 Hematology Colony Stimulating Factors: (OWURPERSDJ 3URPDFWDŠ z NORMAL RESPONSE F5 Non Factor V Leiden WT/WT Carrier 2 EXPECTED 3 4 Immunology 5-Aminosalicylic Acid Derivatives: REPORT 6XOIDVDOD]LQH $]XOILGLQHŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 2 due to a risk of hemolytic anemia n 3 4 Immunology Antigout Agents: /HVLQXUDG =XUDPSLFŠ z NORMAL RESPONSE CYP2C9 Normal Metabolizer *1/*1 2 EXPECTED 3 4 Immunology Antirheumatic Immunosuppressants:SAMPLE 0HWKRWUH[DWH 7UH[DOOŠ œ NORMAL RESPONSE ITPA Non-protective Wild WT/WT Type 2 EXPECTED 3 4 Immunology Immunosuppressant Agents: &\FORVSRULQH *HQJUDIŠ œ INCREASE DOSE CYP3A5 Expresser *1A/*3A 6LUROLPXV 5DSDPXQHŠ œ 2 3 Immunology Immunosuppressant Agents: 7DFUROLPXV 3URJUDIŠ œ INCREASE DOSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 27 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Immunology Immunosuppressant Agents: 7DFUROLPXV 3URJUDIŠ œ INCREASE DOSE CYP3A5 Expresser *1A/*3A 2 with 1.5 to 2 times recommended starting dose not 3 exceed 0.3mg per kg per day 4 Immunology Immunosuppressive Drugs: $]DWKLRSULQH ,PXUDQŠ z NORMAL RESPONSE TPMT Normal Metabolizer *1/*1 2 EXPECTED 3 4 Immunology Systemic Corticosteroids: 0HWK\OSUHGQLVRORQH 0HGUROŠ œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 3UHGQLVRORQH 2UDSUHGŠ œ genotype 3UHGQLVRQH 'HOWDVRQHŠ œ 2 Immunology Urate-Oxidase (Recombinent): 3HJORWLFDVH .U\VWH[[DŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 2 due to the risk of hemolysis and n 3 methemoglobinemia 4 Immunology Uricosuric Agents: REPORT Probenecid z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 2 due to the risk of hemolysis and n 3 methemoglobinemia 4 Immunology Xanthine Oxidase Inhibitors: $OORSXULQRO =\ORSULPŠ z NORMAL RESPONSE HLA-B Wild Type WT/WT 2 EXPECTED 3 4 Infectious Antifungal Drugs: Diseases SAMPLE 9RULFRQD]ROH 9IHQGŠ z NORMAL RESPONSE CYP2C19 Intermediate Metabolizer *1/*2 2 EXPECTED 3 4 Infectious Antihepaciviral Drugs: Diseases %RFHSUHYLU 9LFWUHOLVŠ z USE CAUTION IFNL3 Unfavorable Response 39738787C>T/39 Genotype /HGLSDVYLU6RIRVEXYLU +DUYRQLŠ z due to decreased response and 743165T>G 3HJLQWHUIHURQDOIDE 3HJ,QWURQŠ z increased likelihood of relapse 5LEDYLULQ &RSHJXVŠ œ 7HODSUHYLU ,QFLYRŠ z Infectious Antihepaciviral Drugs: Diseases %RFHSUHYLU 9LFWUHOLVŠ { USE CAUTION ITPA Non-protective Wild WT/WT Type 3HJLQWHUIHURQDOIDE 3HJ,QWURQŠ œ due to increased risk of ribavirin- 5LEDYLULQ &RSHJXVŠ œ induced hemolytic anemia 7HODSUHYLU ,QFLYRŠ { PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 28 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Infectious Antimalarial Drugs: Diseases &KORURTXLQH $UDOHQŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea Primaquine Phosphate z due to high risk for hemolysis n 3ULPDTXLQHŠ 4XLQLQH 4XDODTXLQŠ z 2 Infectious Antiretroviral Drugs: Diseases (IDYLUHQ] 6XVWLYDŠ z USE CAUTION CYP2B6 G516T G516T/G516T/A7 Homozygous/A785G 1HYLUDSLQH 9LUDPXQHŠ œ due to higher potential for an 85G/A785G Homozygous 2 increased frequency and severity of drug-associated adverse 3 events Infectious Antiretroviral Drugs: Diseases $EDFDYLU =LDJHQŠ z NORMAL RESPONSE HLA-B Wild Type WT/WT 2 EXPECTED 3 4 Infectious Antiretroviral Drugs: Diseases $WD]DQDYLU 5H\DWD]Š œ NORMAL RESPONSE UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 EXPECTED 3 4 Infectious Antiretroviral Drugs: REPORT Diseases 'ROXWHJUDYLU 7LYLFD\Š z NORMAL RESPONSE UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 EXPECTED 3 4 Infectious Antiretroviral Drugs: Diseases /DPLYXGLQH (SLYLUŠ œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA /RSLQDYLU5LWRQDYLU .DOHWUDŠ œ genotype =LGRYXGLQH 5HWURYLUŠ œ 2 Infectious Antiretroviral Drugs:SAMPLE Diseases 1HOILQDYLU 9LUDFHSWŠ z NORMAL RESPONSE CYP2C19 Intermediate Metabolizer *1/*2 2 EXPECTED 3 4 Infectious Antitubercular Agents: Diseases (WKDPEXWRO 0\DPEXWROŠ œ NORMAL RESPONSE NAT2 Rapid Acetylator *4/*12 Isoniazid z EXPECTED 3\UD]LQDPLGH 5LIDWHUŠ z 5LIDPSLQ 5LIDGLQŠ z Infectious Lipopeptides: Diseases 'DSWRP\FLQ &XELFLQŠ œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 2 genotype 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 29 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Infectious Macrolides: Diseases Erythromycin/Sulfisoxazole z DECREASE DOSE G6PD G6PD Deficiency 3HGLD]ROHŠ WT/Mediterranea due to a risk of hemolytic anemia n 2 3 4 Infectious Miscellaneous Antibiotics: Diseases Dapsone z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea Sulfamethoxazole/Trimethoprim z due to an increased risk of n %DFWULPŠ hemolytic adverse reactions 2 3 Infectious Miscellaneous Antibiotics: Diseases 1DOLGL[LF$FLG 1HJJUDPŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 1LWURIXUDQWRLQ 0DFURELGŠ z due to an association with n 2 hemolytic anemia 3 Infectious Topical Antibiotics: Diseases 0DIHQLGH 6XOIDP\ORQŠ z CONSIDER ALTERNATIVES G6PD G6PD Deficiency WT/Mediterranea 5 due to reported fatal ADR cases n 2 3 REPORT 4 Neurology Acetylcholinesterase Inhibitors: 'RQHSH]LO $ULFHSWŠ z USE CAUTION CYP2D6 Intermediate Metabolizer *4/*10 2 due to possible increased ADRs 3 caused by decreased drug metabolism 4 Neurology Acetylcholinesterase Inhibitors: *DODQWDPLQH 5D]DG\QHŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 SAMPLEEXPECTED 3 4 Neurology Anticonvulsant Drugs: %ULYDUDFHWDP %ULYLDFWŠ z USE CAUTION CYP2C19 Intermediate Metabolizer *1/*2 2 due to possible increased ADRs 3 4 Neurology Anticonvulsant Drugs: &DUEDPD]HSLQH 7HJUHWROŠ œ NORMAL RESPONSE SCN2A rs2304016 non-GG WT/WT genotype /DPRWULJLQH /DPLFWDOŠ œ EXPECTED 2[FDUED]HSLQH 7ULOHSWDOŠ œ 3KHQ\WRLQ 'LODQWLQŠ œ 7RSLUDPDWH 7RSDPD[Š œ

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 30 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Neurology Anticonvulsant Drugs: &DUEDPD]HSLQH 7HJUHWROŠ z NORMAL RESPONSE HLA-B Wild Type WT/WT 3KHQ\WRLQ 'LODQWLQŠ z EXPECTED 2 3 Neurology Anticonvulsant Drugs: &ORED]DP 2QILŠ z NORMAL RESPONSE CYP2C19 Intermediate Metabolizer *1/*2 2 EXPECTED 3 4 Neurology Anticonvulsant Drugs: Phenobarbital œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 2 genotype 3 4 Neurology Anticonvulsant Drugs: 9DOSURLF$FLG 'HSDNRWHŠ œ NORMAL RESPONSE ANKK1 A1 Heterozygous WT/c.2137G>A 2 EXPECTED 3 4 Neurology Antimigraine Agents: (OHWULSWDQ 5HOSD[Š { NORMALREPORT RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Neurology Antimigraine Agents: =ROPLWULSWDQ =RPLJŠ { NORMAL RESPONSE CYP1A2 Normal Metabolizer *1A/*1F 2 EXPECTED 3 4 Neurology Central Monoamine-Depleting Agents: 7HWUDEHQD]LQH ;HQD]LQHŠ SAMPLEz NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Neurology COMT Inhibitors: (QWDFDSRQH &RPWDQŠ œ NORMAL RESPONSE COMT Non MET Homozygous WT/WT 2 EXPECTED 3 4 Neurology NMDA Receptor Antagonists: Dextromethorphan/Quinidine z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer 1XHGH[WDŠ EXPECTED *4/*10 2 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 31 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Oncology Alkylating Agents: &\FORSKRVSKDPLGH &\WR[DQŠ œ USE CAUTION MTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 2 due to poorer response and 298C Homozygous Mutation 3 increased risk of toxicity 4 Oncology Alkylating Agents: &\FORSKRVSKDPLGH &\WR[DQŠ œ USE CAUTION NQO1 rs1800566 AA genotype c.559C>T/c.559C 2 due to worse outcome including >T 3 overall survival and progression- free survival 4 Oncology Anthracyclines: 'R[RUXELFLQ 'R[LOŠ œ USE CAUTION NQO1 rs1800566 AA genotype c.559C>T/c.559C 2 due to worse outcome including >T 3 overall survival and progression- free survival 4 Oncology Anthracyclines: (SLUXELFLQ (OOHQFHŠ œ USE CAUTION NQO1 rs1800566 AA genotype c.559C>T/c.559C 2 due to worse outcome including >T 3 overall survival and progression- free survival 4 Oncology Antiemetics: 'H[DPHWKDVRQH 'HFDGURQŠ œ NORMALREPORT RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 2 genotype 3 4 Oncology Antiemetics: 'URQDELQRO 0DULQROŠ z NORMAL RESPONSE CYP2C9 Normal Metabolizer *1/*1 2 EXPECTED 3 4 Oncology Antiemetics (Selective 5-HT3 Receptor Antagonist): 'RODVHWURQ $Q]HPHWŠ SAMPLEœ NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 *UDQLVHWURQ 6DQFXVRŠ œ EXPECTED 2 3 Oncology Antiemetics (Selective 5-HT3 Receptor Antagonist): 'RODVHWURQ $Q]HPHWŠ œ NORMAL RESPONSE NOS1AP rs10494366 GG EXPECTED WT/WT genotype/rs10800397 C *UDQLVHWURQ 6DQFXVRŠ œ Allele 2 Carrier/rs10919035 C Allele Carrier 3 Oncology Antiemetics (Selective 5-HT3 Receptor Antagonist): 2QGDQVHWURQ =RIUDQŠ œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 2 genotype 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 32 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Oncology Antiemetics (Selective 5-HT3 Receptor Antagonist): 2QGDQVHWURQ =RIUDQŠ œ NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Oncology Antiemetics (Selective 5-HT3 Receptor Antagonist): 3DORQRVHWURQ $OR[LŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Oncology Antimetabolites (Purine Analog): 0HUFDSWRSXULQH 3XULQHWKROŠ z NORMAL RESPONSE TPMT Normal Metabolizer *1/*1 7KLRJXDQLQH 7DEORLGŠ z EXPECTED 2 3 Oncology Antimetabolites (Pyrimidine Analog): )OXRURXUDFLO &DUDFŠ œ USE CAUTION ABCB1 rs2032582 AA WT/WT genotype/rs1045642 AA 2 due to increased risk of diarrhea genotype 3 4 Oncology Antimetabolites (Pyrimidine Analog): )OXRURXUDFLO &DUDFŠ œ USE CAUTIONREPORTERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA 2 due to an increased risk for genotype/rs735482 AA 3 nephrotoxicity, decreased genotype survival and a poorer response 4 Oncology Antimetabolites (Pyrimidine Analog): )OXRURXUDFLO &DUDFŠ œ USE CAUTION GSTP1 rs1695 AA genotype WT/WT 2 due to a highly increased risk of 3 toxicity and poorer treatment outcome 4 Oncology Antimetabolites (Pyrimidine Analog): )OXRURXUDFLO &DUDFŠ SAMPLEœ USE CAUTION MTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 2 due to poorer response and 298C Homozygous Mutation 3 increased risk of toxicity 4 Oncology Antimetabolites (Pyrimidine Analog): )OXRURXUDFLO &DUDFŠ œ USE CAUTION NQO1 rs1800566 AA genotype c.559C>T/c.559C 2 due to worse outcome including >T 3 overall survival and progression- free survival 4 Oncology Antimetabolites (Pyrimidine Analog): )OXRURXUDFLO &DUDFŠ œ USE CAUTION XRCC1 rs25487 T Allele Carrier WT/WT 2 due to decreased survival and 3 response 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 33 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Oncology Antimetabolites (Pyrimidine Analog): &DSHFLWDELQH ;HORGDŠ z NORMAL RESPONSE DPYD Normal Metabolizer EXPECTED *5/*9A/c.496A>G/ 3\ULPLGLQHGLRQH 7HJDIXU8UDFLOŠ œ IVS10-15T>C 2 3 Oncology Antimetabolites (Pyrimidine Analog): &\WDUDELQH 'HSRF\WŠ œ NORMAL RESPONSE CDA rs532545 C Allele WT/WT 2 EXPECTED 3 4 Oncology BCR-ABL Tyrosine Kinase Inhibitors: 1LORWLQLE 7DVLJQDŠ z NORMAL RESPONSE UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 3D]RSDQLE 9RWULHQWŠ z EXPECTED 2 3 Oncology BRAF Kinase Inhibitors: 'DEUDIHQLE 7DILQODUŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 2 by closely observing patients n 3 with G6PD deficiency for signs of hemolytic anemia 4 Oncology Chemotherapy Modulating Agents: /HXFRYRULQ :HOOFRYRULQŠ œ USE CAUTIONREPORTERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA 2 due to an increased risk for genotype/rs735482 AA 3 nephrotoxicity, decreased genotype survival and a poorer response 4 Oncology Chemotherapy Modulating Agents: /HXFRYRULQ :HOOFRYRULQŠ { USE CAUTION GSTP1 rs1695 AA genotype WT/WT 2 due to a highly increased risk of 3 toxicity and poorer treatment outcome 4 Oncology Chemotherapy Modulating Agents: /HXFRYRULQ :HOOFRYRULQŠ SAMPLEœ USE CAUTION MTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 2 due to poorer response and 298C Homozygous Mutation 3 increased risk of toxicity 4 Oncology Chemotherapy Modulating Agents: /HXFRYRULQ :HOOFRYRULQŠ { USE CAUTION XRCC1 rs25487 T Allele Carrier WT/WT 2 due to decreased survival and 3 response 4 Oncology EGFR Tyrosine Kinase Inhibitors: (UORWLQLE 7DUFHYDŠ œ NORMAL RESPONSE UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 EXPECTED 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 34 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Oncology EGFR Tyrosine Kinase Inhibitors: *HILWLQLE ,UHVVDŠ œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Oncology EGFR Tyrosine Kinase Inhibitors: 5X[ROLWLQLE -DNDYLŠ œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Oncology Folate Antimetabolites: 0HWKRWUH[DWH 7UH[DOOŠ œ USE CAUTION ABCB1 rs2032582 AA WT/WT genotype/rs1045642 AA 2 due to increased risk of toxicity genotype 3 caused by increased drug concentration 4 Oncology Folate Antimetabolites: 0HWKRWUH[DWH 7UH[DOOŠ œ USE CAUTION MTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 2 due to poorer response and 298C Homozygous Mutation 3 increased risk of toxicity 4 Oncology Folate Antimetabolites: 3HPHWUH[HG $OLPWDŠ œ USE CAUTIONREPORTMTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 2 due to poorer response and 298C Homozygous Mutation 3 increased risk of toxicity 4 Oncology Histone Deacetylase (HDAC) Inhibitors: %HOLQRVWDW %HOHRGDTŠ z NORMAL RESPONSE UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 EXPECTED 3 4 Oncology Immunomodulators: 7KDOLGRPLGH 7KDORPLGŠ SAMPLEœ USE CAUTION ERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA 2 due to decreased overall survival genotype/rs735482 AA 3 genotype 4 Oncology Platinum Analog: &DUERSODWLQ 3DUDSODWLQŠ œ USE CAUTION ERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA &LVSODWLQ 3ODWLQROŠ œ due to an increased risk for genotype/rs735482 AA 2[DOLSODWLQ (OR[DWLQŠ œ nephrotoxicity, decreased genotype survival and a poorer response 2 Oncology Platinum Analog: &DUERSODWLQ 3DUDSODWLQŠ œ USE CAUTION GSTP1 rs1695 AA genotype WT/WT &LVSODWLQ 3ODWLQROŠ œ due to a highly increased risk of 2[DOLSODWLQ (OR[DWLQŠ œ toxicity and poorer treatment outcome 2

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 35 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Oncology Platinum Analog: &DUERSODWLQ 3DUDSODWLQŠ œ USE CAUTION XRCC1 rs25487 T Allele Carrier WT/WT &LVSODWLQ 3ODWLQROŠ œ due to decreased survival and 2[DOLSODWLQ (OR[DWLQŠ œ response 2 Oncology Platinum Analog: &DUERSODWLQ 3DUDSODWLQŠ œ USE CAUTION MTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 2[DOLSODWLQ (OR[DWLQŠ œ due to poorer response and 298C Homozygous Mutation 2 increased risk of toxicity 3 Oncology Platinum Analog: &LVSODWLQ 3ODWLQROŠ œ USE CAUTION NQO1 rs1800566 AA genotype c.559C>T/c.559C 2[DOLSODWLQ (OR[DWLQŠ œ due to worse outcome including >T 2 overall survival and progression- free survival 3 Oncology Platinum Analog: &LVSODWLQ 3ODWLQROŠ œ USE CAUTION ERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA 2 due to increased risk for genotype/rs735482 AA 3 nephrotoxicity genotype 4 Oncology Selective Estrogen Receptor Modulators (SERMs): 7DPR[LIHQ 6ROWDPR[Š œ CONSIDERREPORT ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 5 like aromatase inhibitor for postmenopausal women due to 2 increased risk for relapse of 3 breast cancer 4 Oncology Taxane Derivatives: 'RFHWD[HO 7D[RWHUHŠ œ USE CAUTION ERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA 2 due to increased risk for genotype/rs735482 AA 3 nephrotoxicity genotype 4 SAMPLE Oncology Taxane Derivatives: 3DFOLWD[HO $EUD[DQHŠ œ USE CAUTION ERCC1 rs3212986 C Allele WT/WT Carrier/rs11615 AA 2 due to increased risk for genotype/rs735482 AA 3 nephrotoxicity genotype 4 Oncology Taxane Derivatives: &DED]LWD[HO -HYWDQDŠ œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 36 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Oncology Topoisomerase I Inhibitors: ,ULQRWHFDQ &DPSWRVDUŠ z NORMAL RESPONSE UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 EXPECTED 3 4 Oncology Topoisomerase II Inhibitors: ,GDUXELFLQ ,GDP\FLQŠ œ NORMAL RESPONSE SLCO1B1 Normal Activity *1/*1 2 EXPECTED 3 4 Oncology Urate-Oxidases (Recombinant): 5DVEXULFDVH (OLWHNŠ z CONSIDER ALTERNATIVES G6PD G6PD Deficiency WT/Mediterranea 5 include allopurinol n 2 3 4 Oncology VEGF Tyrosine Kinase Inhibitors: 6RUDIHQLE 1H[$YDUŠ œ USE CAUTION UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 due to increased risk of 3 hyperbilirubinemia and treatment interruption 4 REPORT Oncology VEGF Tyrosine Kinase Inhibitors: 6XQLWLQLE 6XWHQWŠ œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Oncology Vinca Alkaloids: 9LQFULVWLQH 0DUTLERŠ œ NORMAL RESPONSE ABCB1 rs2032582 AA EXPECTED WT/WT genotype/rs1045642 AA 2 genotype 3 4 SAMPLE Osteoporosis Selective Estrogen Receptor Modulators (SERMs): 5DOR[LIHQH (YLVWDŠ œ USE CAUTION UGT1A1 Heterozygous *28 Allele *1/*28 Carrier 2 due to decreased hip bone 3 mineral density 4 Pain Management Alpha-2 Adrenergic Agonists: 7L]DQLGLQH =DQDIOH[Š { NORMAL RESPONSE CYP1A2 Normal Metabolizer *1A/*1F 2 EXPECTED 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 37 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Pain Management Nonsteroidal Antiinflammatory Drugs (NSAIDs): &HOHFR[LE &HOHEUH[Š z NORMAL RESPONSE CYP2C9 Normal Metabolizer *1/*1 'LFORIHQDF 9ROWDUHQŠ œ EXPECTED 0HOR[LFDP 0RELFŠ œ 2 Pain Management Nonsteroidal Antiinflammatory Drugs (NSAIDs): ,EXSURIHQ $GYLOŠ { NORMAL RESPONSE CYP2C9 Normal Metabolizer *1/*1 1DSUR[HQ $OHYHŠ { EXPECTED 2 3 Pain Management Nonsteroidal Antiinflammatory Drugs (NSAIDs): 3LUR[LFDP )HOGHQHŠ z NORMAL RESPONSE CYP2C9 Normal Metabolizer *1/*1 2 EXPECTED 3 4 Pain Management Opioids: &RGHLQH &RGHLQHŠ œ CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 Codeine/Acetaminophen (Tylenol œ if no response  Š Hydrocodone/Acetaminophen œ 9LFRGLQŠ 2[\FRGRQH 2[\FRQWLQŠ œ REPORT 5 Pain Management Opioids: Tramadol z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 Hydrochloride/Acetaminophen (not oxycodone, codeine) 8OWUDFHWŠ 7UDPDGRO 8OWUDPŠ z OR 5 2 3 SAMPLEINCREASE DOSE

Pain Management Opioids: 0HWKDGRQH 0HWKDGRVHŠ œ DECREASE DOSE CYP2B6 G516T G516T/G516T/A7 Homozygous/A785G 2 85G/A785G Homozygous 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 38 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Pain Management Opioids: %XSUHQRUSKLQH 6XEXWH[Š { DECREASE DOSE CYP3A4 Intermediate Metabolizer *1A/*1B )HQWDQ\O 'XUDJHVLFŠ { 6XIHQWDQLO 6XIHQWDŠ { OR 2 USE CAUTION due to the risk of increased exposure to the drug leading to adverse events

Pain Management Opioids: $OIHQWDQLO $OIHQWDŠ œ NORMAL RESPONSE OPRM1 rs1799971 A Allele EXPECTED WT/WT Carrier/rs510679 TT +\GURPRUSKRQH 'LODXGLGŠ { genotype 0RUSKLQH 06&RQWLQŠ œ 2 Pain Management Skeletal Muscle Relaxants: &DULVRSURGRO 6RPDŠ œ NORMAL RESPONSE CYP2C19 Intermediate Metabolizer *1/*2 2 EXPECTED 3 4 Pain Management Skeletal Muscle Relaxants: &\FOREHQ]DSULQH )OH[HULOŠ { NORMAL RESPONSE CYP1A2 Normal Metabolizer EXPECTEDREPORT*1A/*1F 2 3 4 Psychiatry Aldehyde Dehydrogenase Inhibitors: 'LVXOILUDP $QWDEXVHŠ œ NORMAL DOSE ANKK1 A1 Heterozygous WT/c.2137G>A 2 may have an increased 3 likelihood of response 4 Psychiatry Alpha-2 Antagonists: 0LUWD]DSLQH 5HPHURQŠ œ USE CAUTION CYP2D6 Intermediate Metabolizer SAMPLE *4/*10 2 due to possible increased ADRs 3 4 Psychiatry Anti-Anxiety Agents: %XVSLURQH %XVSDUŠ { NORMAL RESPONSE HTR1A rs6295 CC EXPECTED WT/WT genotype/rs1800044 C 2 Allele Carrier 3 4 Psychiatry Antimanic Agents: /LWKLXP /LWKRELGŠ œ USE CAUTION ABCB1 rs2032582 AA WT/WT genotype/rs1045642 AA 2 due to possible less drug genotype 3 response 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 39 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Psychiatry Antipsychotics: 5LVSHULGRQH 5LVSHUGDOŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 5 (e.g., quetiapine, olanzapine, clozapine) 2 3 4 Psychiatry Antipsychotics: 7KLRULGD]LQH 0HOODULOŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 5 2 3 4 Psychiatry Antipsychotics: Chlorpromazine œ USE CAUTION CYP1A2 Normal Metabolizer *1A/*1F Fluphenazine œ due to possible increased QT 2 interval 3 Psychiatry Antipsychotics: &OR]DSLQH &OR]DULOŠ œ USE CAUTION ANKK1 A1 Heterozygous WT/c.2137G>A 2 due to increased risk of side effects includingREPORT 3 hyperprolactinemia and weight 4 gain Psychiatry Antipsychotics: &OR]DSLQH &OR]DULOŠ œ USE CAUTION HTR2C rs1414334 C Allele WT/WT Carrier 2 due to increased risk of 3 developing metabolic syndrome 4 Psychiatry Antipsychotics: 2ODQ]DSLQH =\SUH[DŠ œ USE CAUTION SLC6A4 HTTLPR Long Form LA/LA 4XHWLDSLQH 6HURTXHOŠ SAMPLEœ due to increased risk of side 2 effects 3 Psychiatry Antipsychotics: 2ODQ]DSLQH =\SUH[DŠ œ USE CAUTION ANKK1 A1 Heterozygous WT/c.2137G>A 2 due to increased risk of side 3 effects including hyperprolactinemia and weight 4 gain Psychiatry Antipsychotics: 2ODQ]DSLQH =\SUH[DŠ œ USE CAUTION HTR2C rs1414334 C Allele WT/WT Carrier 2 due to increased risk of 3 developing metabolic syndrome 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 40 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Psychiatry Antipsychotics: $ULSLSUD]ROH $ELOLI\Š z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 %UH[SLSUD]ROH 5H[XOWLŠ z EXPECTED ,ORSHULGRQH )DQDSWŠ z 3LPR]LGH 2UDSŠ z Psychiatry Antipsychotics: $ULSLSUD]ROH $ELOLI\Š œ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Psychiatry Antipsychotics: +DORSHULGRO +DOGROŠ œ NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Psychiatry Antipsychotics: Perphenazine z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Psychiatry Benzodiazepines: 'LD]HSDP 9DOLXPŠ z USE CAUTIONREPORTCYP2C19 Intermediate Metabolizer *1/*2 2 due to possible increased ADRs 3 4 Psychiatry Benzodiazepines: $OSUD]RODP ;DQD[Š { NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Psychiatry Benzodiazepines: /RUD]HSDP $WLYDQŠ SAMPLEœ NORMAL RESPONSE UGT2B15 rs1902023 non-AA *1/*2 genotype 2[D]HSDP 6HUD[Š œ EXPECTED 2 3 Psychiatry Benzodiazepines: 0LGD]RODP 9HUVHGŠ œ NORMAL RESPONSE CYP3A5 Expresser *1A/*3A 2 EXPECTED 3 4 Psychiatry CNS Stimulants (ADHD): 'H[WURDPSKHWDPLQH $GGHUDOOŠ œ USE CAUTION DRD1 rs4532 CC genotype WT/WT 0HWK\OSKHQLGDWH 5LWDOLQŠ œ due to increased severity of 2 social withdrawal 3

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 41 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Psychiatry CNS Stimulants (ADHD): $PSKHWDPLQH $GGHUDOOŠ œ NORMAL RESPONSE COMT Non MET Homozygous WT/WT 'H[PHWK\OSKHQLGDWH )RFDOLQŠ œ EXPECTED /LVGH[DPIHWDPLQH 9\YDQVHŠ { 2 Psychiatry CNS Stimulants (ADHD): $PSKHWDPLQH $GGHUDOOŠ œ NORMAL RESPONSE OPRM1 rs1799971 A Allele EXPECTED WT/WT Carrier/rs510679 TT 2 genotype 3 4 Psychiatry CNS Stimulants (ADHD): 0HWKDPSKHWDPLQH 'HVR[\QŠ œ NORMAL RESPONSE FAAH rs324420 CC genotype WT/WT 2 EXPECTED 3 4 Psychiatry Dopamine/Norepinephrine-Reuptake Inhibitors: %XSURSLRQ :HOOEXWULQŠ œ USE CAUTION CYP2B6 G516T G516T/G516T/A7 Homozygous/A785G 2 due to reduced response and 85G/A785G Homozygous 3 increased risk of side effects 4 Psychiatry Dopamine/Norepinephrine-Reuptake Inhibitors: %XSURSLRQ :HOOEXWULQŠ œ USE CAUTIONREPORTCYP2C19 Intermediate Metabolizer *1/*2 2 due to reduced response and 3 increased risk of side effects 4 Psychiatry Opioids Antagonists: 1DOR[RQH (Y]LRŠ œ NORMAL RESPONSE OPRM1 rs1799971 A Allele EXPECTED WT/WT Carrier/rs510679 TT 1DOWUH[RQH 5HYLDŠ œ genotype 2 3 Psychiatry Other Stimulants: Cannabinoids SAMPLEœ USE CAUTION FAAH rs324420 CC genotype WT/WT 2 due to increased risk of 3 tetrahydrocannabinol (THC) dependence 4 Psychiatry Other Stimulants: Cocaine œ NORMAL RESPONSE CNR1 rs806368 non-TT EXPECTED c.*3475A>G/c.*34 genotype 2 75A>G 3 4 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): &LWDORSUDP &HOH[DŠ œ USE CAUTION GRIK4 rs1954787 T Allele WT/WT Carrier 2 due to reduced response 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 42 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): )OXR[HWLQH 3UR]DFŠ z USE CAUTION CYP2D6 Intermediate Metabolizer *4/*10 2 due to elevated risk for drug 3 overdose resulting in adverse events and drug interaction 4 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): )OXYR[DPLQH /XYR[Š œ USE CAUTION HTR1A rs6295 CC WT/WT genotype/rs1800044 C 3DUR[HWLQH 3D[LOŠ œ due to reduced response Allele Carrier 6HUWUDOLQH =RORIWŠ œ 2 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): 6HUWUDOLQH =RORIWŠ œ USE CAUTION CYP2C19 Intermediate Metabolizer *1/*2 2 with high alert to adverse drug 3 events 4 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): (VFLWDORSUDP /H[DSURŠ z NORMAL RESPONSE CYP2C19 Intermediate Metabolizer *1/*2 2 EXPECTED 3 4 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): (VFLWDORSUDP /H[DSURŠ œ NORMALREPORT RESPONSE SLC6A4 HTTLPR Long Form LA/LA 2 EXPECTED 3 4 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): 9LOD]RGRQH 9LLEU\GŠ { NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Psychiatry Selective Serotonin Reuptake Inhibitors (SSRIs): 9RUWLR[HWLQH 7ULQWHOOL[Š SAMPLEz NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 9HQODID[LQH (IIH[RUŠ z CONSIDER ALTERNATIVES CYP2D6 Intermediate Metabolizer *4/*10 5 (e.g., citalopram, sertraline) 2 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 43 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 0LOQDFLSUDQ 6DYHOODŠ œ USE CAUTION ADRA2A rs1800544 GG WT/c.-217G>A genotype/rs1800545 GA 2 due to reduced response genotype 3 4 Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 0LOQDFLSUDQ 6DYHOODŠ œ USE CAUTION HTR1A rs6295 CC WT/WT genotype/rs1800044 C 2 due to reduced response Allele Carrier 3 4 Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): $WRPR[HWLQH 6WUDWWHUDŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4 Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 'XOR[HWLQH &\PEDOWDŠ { NORMAL RESPONSE CYP1A2 Normal Metabolizer *1A/*1F 2 EXPECTED 3 4 Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): /HYRPLOQDFLSUDQ )HW]LPDŠ { NORMALREPORT RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Psychiatry Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): 5HER[HWLQH (GURQD[Š { NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Psychiatry Serotonin Reuptake Inhibitors/Antagonists: 7UD]RGRQH 'HV\UHOŠ SAMPLE{ NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Psychiatry Tetracyclic Antidepressants: Maprotiline œ DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 2 3 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 44 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Psychiatry Tricyclic Antidepressants: $PLWULSW\OLQH (ODYLOŠ z DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 &ORPLSUDPLQH $QDIUDQLOŠ z by 25% 'R[HSLQ 6LOHQRUŠ z ,PLSUDPLQH 7RIUDQLOŠ z 3URWULSW\OLQH 9LYDFWLOŠ z 7ULPLSUDPLQH 6XUPRQWLOŠ z Psychiatry Tricyclic Antidepressants: 'HVLSUDPLQH 1RUSUDPLQŠ z DECREASE DOSE CYP2D6 Intermediate Metabolizer *4/*10 1RUWULSW\OLQH 3DPHORUŠ z by 25% 2 3 Rheumatology Nonsteroidal Antiinflammatory Drugs (NSAIDs): )OXUELSURIHQ $QVDLGŠ z NORMAL RESPONSE CYP2C9 Normal Metabolizer *1/*1 2 EXPECTED 3 4 Smoking Smoking Cessation Aids: Cessation %XSURSLRQ =\EDQŠ œ USE CAUTION ANKK1 A1 Heterozygous WT/c.2137G>A 2 due to reduced effectiveness 3 4 REPORT Smoking Smoking Cessation Aids: Cessation 1LFRWLQH 1LFRGHUPŠ œ NORMAL RESPONSE COMT Non MET Homozygous WT/WT 2 EXPECTED 3 4 Supplements Vitamins: Folic Acid œ CONSIDER ALTERNATIVES MTHFR A1298C Heterozygous C677T/C677T/A1 Mutation/C677T 5 (e.g., supplements containing 298C Homozygous Mutation methylfolate) due to significantly 2 SAMPLEreduced folic acid conversion 3 4 Toxicology Antidotes: Sodium Nitrite z CONSIDER ALTERNATIVES G6PD G6PD Deficiency WT/Mediterranea 5 n 2 3 4 Toxicology Antidotes: Ethanol œ USE CAUTION ANKK1 A1 Heterozygous WT/c.2137G>A 2 due to increased risk for 3 alcoholism 4

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 45 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Therapeutic Drug Impacted Evidence Clinical Interpretation Gene/Genotype Phenotype Level Toxicology Antidotes: 0HWK\OHQH%OXH 3URYD\EOXHŠ z USE CAUTION G6PD G6PD Deficiency WT/Mediterranea 2 due to risk of hemolytic anemia n 3 4 Urology Alpha 1 Blockers: 'XWDVWHULGH7DPVXORVLQ -DO\QŠ z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 7DPVXORVLQ )ORPD[Š z EXPECTED 2 3 Urology Alpha 1 Blockers: 6LORGRVLQ 5DSDIORŠ { NORMAL RESPONSE CYP3A4 Intermediate Metabolizer *1A/*1B 2 EXPECTED 3 4 Urology Anticholinergic Agents: 'DULIHQDFLQ (QDEOH[Š z NORMAL RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 )HVRWHURGLQH 7RYLD]Š z EXPECTED 2 3 Urology Anticholinergic Agents: 7ROWHURGLQH 'HWUROŠ z NORMALREPORT RESPONSE CYP2D6 Intermediate Metabolizer *4/*10 2 EXPECTED 3 4

SAMPLE

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 46 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Patient PGxPsych™ Genotype and Phenotype Results for Test, Matthew

Gene Genotype Phenotype

ABCB1 WT/WT rs2032582 AA genotype/rs1045642 AA genotype

ACE WT/WT ACE Deletion

ADRA2A WT/c.-217G>A rs1800544 GG genotype/rs1800545 GA genotype

AGTR1 WT/WT rs5186 AA genotype

ANKK1 WT/c.2137G>A A1 Heterozygous

APOB c.8216C>T/c.8216C>T rs676210 AA Genotype

APOE WT/WT Non E2 Carrier

ATM WT/WT rs11212617 CC genotype

CDA WT/WT rs532545 C Allele

CES1 WT/WT rs71647871 C Allele CNR1 c.*3475A>G/c.*3475A>G REPORTrs806368 non-TT genotype COMT WT/WT Non MET Homozygous

CYP1A2 *1A/*1F Normal Metabolizer

CYP2B6 G516T/G516T/A785G/A785G G516T Homozygous/A785G Homozygous

CYP2C19 *1/*2 Intermediate Metabolizer

CYP2C8 *1/*1 Wild Type CYP2C9 *1/*1SAMPLE Normal Metabolizer CYP2D6 *4/*10 Intermediate Metabolizer

CYP3A4 *1A/*1B Intermediate Metabolizer

CYP3A5 *1A/*3A Expresser

CYP4F2 *1/*1 Normal Metabolizer

DPYD *5/*9A/c.496A>G/IVS10-15T>C Normal Metabolizer

DRD1 WT/WT rs4532 CC genotype

DRD2 WT/WT rs1799978 TT genotype

rs3212986 C Allele Carrier/rs11615 AA ERCC1 WT/WT genotype/rs735482 AA genotype

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 47 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Gene Genotype Phenotype

F2 WT/WT Wild Type

F5 WT/WT Non Factor V Leiden Carrier

FAAH WT/WT rs324420 CC genotype

G6PD WT/Mediterranean G6PD Deficiency

GRIK4 WT/WT rs1954787 T Allele Carrier

GSTP1 WT/WT rs1695 AA genotype

HFE WT/c.340+4T>C rs2071303 C Allele Carrier

HLA-B WT/WT Wild Type

HTR1A WT/WT rs6295 CC genotype/rs1800044 C Allele Carrier

HTR2A WT/WT rs7997012 non-GG genotype

HTR2C WT/WT rs1414334 C Allele Carrier

IFNL3 39738787C>T/39743165T>G Unfavorable Response Genotype

ITPA WT/WT Non-protective Wild Type

KIF6 WT/WT REPORTrs20455 AA genotype

LDLR c.1773C>T/c.1773C>T rs688 TT Genotype

A1298C Heterozygous Mutation/C677T Homozygous MTHFR C677T/C677T/A1298C Mutation

NAT2 *4/*12 Rapid Acetylator

rs10494366 GG genotype/rs10800397 C Allele NOS1AP WT/WT Carrier/rs10919035 C Allele Carrier

NQO1 c.559C>T/c.559C>TSAMPLE rs1800566 AA genotype

OPRM1 WT/WT rs1799971 A Allele Carrier/rs510679 TT genotype

SCN2A WT/WT rs2304016 non-GG genotype

SLC6A4 LA/LA HTTLPR Long Form

SLCO1B1 *1/*1 Normal Activity

TPMT *1/*1 Normal Metabolizer

UGT1A1 *1/*28 Heterozygous *28 Allele Carrier

UGT2B15 *1/*2 rs1902023 non-AA genotype

VKORC1 WT/-1639G>A rs9923231 A Allele Carrier

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 48 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Gene Genotype Phenotype

XRCC1 WT/WT rs25487 T Allele Carrier

REPORT

SAMPLE

PGxPsych™ Report for Test, Matthew Laboratory Director: Dr. James Dermody CLIS ID: 0005783 CLIA ID: 31D2038676 PFI ID: 8972 Page 49 of 50 Admera Health, LLC 126 Corporate Blvd ā South Plainfield, NJ 07080 +1-908-222-0533ā[email protected]

Assay Methodology and Limitations for PGxPsych™ Panel:

Pharmacogenomics testing to assess how a patient may respond to prescribed drugs was performed by massively parallel Next Generation Sequencing (NGS). PGxPsych™ was developed, and assessed for accuracy and precision by Admera Health, South Plainfield NJ. The sensitivity and specificity of this test is 100% and 100% respectively. PGxPsych™ has not been cleared or approved by the U.S. Food and Drug Administration (FDA) but the FDA has determined that such clearance or approval is not necessary. The PGxPsych™ test is used for clinical purposes. It should not be regarded as investigational or for research. Drug interaction information is based upon data available in scientific literature and prescribing information for the most commonly prescribed drugs. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing. The DNA testing is not a substitute for clinical monitoring.

The panel includes 53 genes and 214 variants based on the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG) and the FDA's work group guidance. The following genetic variants may be detected in the assay: ABCB1 c.3435T>C, c.2677T>A(G); ACE ACE Insertion; ADRA2A c.1252G>C, c.-217G>A; AGTR1 c.*86A>C; ANKK1 A1; $32%F&!7$32($SRn$70F*!7&'$F&!7&(6F*!$&15F $!*&207F*!$&<3$ $ *1C, *1F, *1K, *3, *4, *6, *7; CYP2B6 A785G, G516T, T983C; CYP2C19 *1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *12, *17; CYP2C8 *3; CYP2C9 *1, *2, *3, *4, *5, *6, *8, *9, *11, *12, *13, *14, *15, *16; CYP2D6 *1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *12, *14, *17, *19, *20, *21, *29, *35, *38, *40, *41, *44, *1XN, *2XN, *4XN, *10XN, *17XN, *29xN, *35xN, *41XN; CYP3A4 *1A, *1B, *2, *3, *12, *17; CYP3A5 *1A, *2, *3A, *3B, *6, *7, *8, *9; CYP4F2 *1, *3; DPYD *1, *2A, *3, *4, *5, *6, *7, *8, *9A, *9B, *10, *11, *12, *13, c.496A>G, IVS10-15T>C, c.1845G>T, c.2846A>T; DRD1 c.- 48G>A; DRD2 c.-585A>G; ERCC1 c.*197G>T, c.354T>C, c.*931T>G; F2 G20210A; F5 c.1601G>A; FAAH c.385C>A; G6PD A, A-202A_376G, A- 376G_968C, Alhambra, Andalus, Beverly Hills, Canton, Cassano, Chatham, Chinese-3, Chinese-4, Coimbra, Cosenza, Fushan, Guadalajara, Ilesha, Iowa, Kaiping, Kalyan, Lagosanto, Mahidol, Mediterran ean, Metaponto, Minnesota, Mt. Sinai, Nara, Nashville, Olomouc, Pawnee, Plymouth, Praba, Puetro Limon, Santamaria, Santiago, Santiago de Cuba, Sao Boria, Shinshu, Sibari, Telti, Tomah, Ube, Union, Viangchan, West Virginia; GRIK4 c.83-10039T>C; GSTP1 c.313A>G; HFE c.340+4T>C; HLA-B *1502, *5701, *5801; HTR1A c.-1019G>C, c.659G>T; HTR2A c.614 -2211T>C; HTR2C c.-759C>T, c.551-3008C>G; IFNL3 g.39738787C>T, g.39743165T>G; ITPA c.94C>A, c.124+21A>C; KIF6 c.2155T>C; LDLR c.1773C>T; MTHFR C677T, A1298C; NAT2 *4, *5, *6, *7, *12, *13; NOS1AP c.106-38510G>T, c.178-20044C>T, c.178-13122C>T; NQO1 c.559C>T; OPRM1 c.118A>G, c.290+1050C>T; SCN2A c.971-32A>G; SLC6A4 5-HTTLPR LA, 5-HTTLPR LG, 5-HTTLPR S; SLCO1B1 *5; TPMT *1, *2, *3A, *3B, *3C, *4; UGT1A1 *28; UGT2B15 *2; VKORC1 c.-1639G>A; XRCC1 c.1196A>G. A normal (wild type) genotype signifies the absence of the targeted alleles and does not indicate the absence of other mutations not covered by the assay. The possibility cannot be ruled out that the indicated genotypes may be present but below the limits of detection for this assay.

General Pharmacogenomics References:

1. Drug labels with pharmacogenomics information: REPORT https://www.pharmgkb.org/view/drug-labels.do

2. Pharmacogenomics drug dosing guidelines: https://www.pharmgkb.org/view/dosing-guidelines.do

3. Clinical Pharmacogenetics Implementation Consortium (CPIC) drug dosing guidelines: https://cpicpgx.org/guidelines

4. FDA drug labels

5. Warfarin dosing guideline: CPIC Guidelines for CYP2C9 andSAMPLE VKORC1 Genotypes and Warfarin Dosing Disclaimer of Liability: The information contained in this report is provided as a service and does not constitute medical advice. At the time of report generation this information is believed to be current and is based upon published research; however, research data evolves and amendments to the prescribing information of the drugs listed will change over time. While this report is believed to be accurate and complete as of the date issued, THE DATA IS PROVIDED "AS IS", WITHOUT WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. As medical advice must be tailored to the specific circumstances of each case, the treating health care professional has ultimate responsibility for all treatment decisions made with regard to a patient including any made on the basis of a patient's genotype.

Electronic Signature

Laboratory Director ABMG Certified, Clinical Molecular Genetics

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