GeneDose Genomic Response Report - Tailor-made …pgenetic.com/wp-content/uploads/2017/04/PersonalizedGeneticTesting... · Patient Information Card Pg. 28 ... Delone, Lasix (Furosem

Personalized Genetic Testing

12855 SW 132 Street Suite 101, Miami, FL 33196

Phone: (786) 732-4679 • Fax: (305) 978-8590

Web: www.pgenetic.com

Laboratory Director: Ana Margarita Espina Hernandez, Ph.D

Patient: Doe, John

Date of Birth: Jan 01, 1955

Gender: Male

Sample ID: 1000.99999

Physician: Test

Practice: Test

Anytown, NJ

Phone: Test

Date Collected: Feb 25, 2016

Date Received: Jan 29, 2016

Date Reported: Apr 11, 2016

Specimen type: Buccal Swab

GeneDose LIVE

Individualized, additional therapeutic decision support

information based on John Doe's genetics, drug regimen,

indications, demographics, and lifestyle indicators are available at

GeneDose™ LIVE via this secured URL:

http://checkdru.gs/

GeneDose Key: dXXHXXF54

Table of Contents

Pg. 1Genetic Summary

Pg. 2Current Regimen Risk Chart

Pg. 3Current Regimen Risk Detail (by severity)

Pg. 10Thrombosis Profile

Pg. 11ApoE Genotype Information

Pg. 12Medications Summary

Pg. 15Medication Report Details (by therapeutic class)

Pg. 27Clinical Evidence Levels

Pg. 28Patient Information Card

AppendixSNP Report

Genetic Summary Information

† When multiple activities are listed, check information in Medication

Report Details (Pg. 15) for specific medication of interest.

Uncertain = No known diplotype/result (name) or activity for this

combination of genetic variants; Uninterpretable Genotype.

Genetic Summary

Gene Result Activity †

ApoE ɛ3|ɛ3 See ApoE Genotype Info.

CYP2C19 *1|*1 Extensive metabolizer


CYP2D6 *5|*41 Intermediate metabolizer

CYP3A4 *1A|*1A Extensive metabolizer

CYP3A5 *3|*3 Poor metabolizer

Factor V Leiden Normal See thrombosis profile

MTHFR (A1298C) Normal See thrombosis profile

MTHFR (C677T) Variant See thrombosis profile

Prothrombin (F2) Normal See thrombosis profile

SLCO1B1 *1|*1 Normal liver uptake

activity

VKORC1 *1|*1 Normal (with respect to

Warfarin)

GeneDose™ Genomic Response Report

1000.99999 - Doe, John - Reported Apr 11, 2016

The information contained in this report is intended to be interpreted by a licensed physician or other licensed healthcare professional. This report is

not intended to take the place of professional medical advice. Decisions regarding use of prescribed medications must be made only after consulting

with a licensed physician or other licensed healthcare professional, and should consider each patient's medical history and current treatment regimen.

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Current Regimen Risk Chart

This chart shows each medication input into GeneDose LIVE for John Doe. The longer a bar is in this chart, the more risky the medication may be.

0 to 5 - Few risks; 6 to 20 - Moderate risk; 20+ - Significant risk

Genetic Drug interaction Anticholinergic burdenLifestyle ADR (Black box) Beers criteria

DUTOPROL (Metoprolol…

Kazano (Alogliptin)

Adderall (Amphetamin…

Aspirin

Delone, Lasix (Furosem…

Coumadin, Jantoven (W…

BuSpar (Buspirone)

0 10025 50 75 125






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Current Regimen Risk Detail

Beers criteriaAnticholinergic burdenADRDrug InteractionLifestyleGeneticSevere Risks

Genetic warning for DUTOPROL (Metoprolol Succinate)

Individuals with intermediate metabolizer status have increased risk of adverse drug reactions. For heart failure (indication):

select alternative drug (e.g. bisoprolol, carvedilol) or reduce dose by 50%. For other indications: be alert to adverse drug

events (e.g. bradycardia, cold extremities) or select alternative drug (e.g. atenolol, bisoprolol).

Kazano (Alogliptin) has its pharmacodynamic parameters altered by DUTOPROL (Metoprolol Succinate)

• use combination with caution

• monitor blood glucose concentration and for changes in glycemic control

Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate

response. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease

and stroke.

American Geriatric Society guidelines

The following products appear on the American Geriatric Society's Beers Criteria for Potentially Inappropriate Medication

Use in Older Adults:

• Amphetamine Aspartate 7.5mg, Amphetamine Sulfate 7.5mg, Dextroamphetamine Saccharate 7.5mg, Dextroamphetamine Sulfate 7.5mg Oral

tablet

• Aspirin 325mg Oral tablet

• Buspirone Hydrochloride 10mg Oral tablet

• Furosemide 20mg Oral tablet

• Metoprolol Succinate 100mg, Hydrochlorothiazide 12.5mg Oral tablet, extended release

Strong regimen anticholinergic burden

The cumulative effect of taking multiple medicines with anticholinergic properties termed as anticholinergic burden can

adversely impact cognition, physical function and increase the risk of mortality.

Beers criteriaAnticholinergic burdenADRDrug InteractionLifestyleGeneticMajor Risks

Aspirin with Alcohol

• avoid combination unless benefit outweighs potential risk

Concomitant ingestion of ethanol with salicylates, especially aspirin, ASA, increases the risk of developing gastric irritation

and GI mucosal bleeding. Ethanol and salicylates are mucosal irritants and aspirin decreases platelet aggregation. Routine

ingestion of ethanol and aspirin can cause significant GI bleeding, which may or may not be overt. Even occasional






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concomitant use of salicylates and ethanol should be avoided. Chronic alcoholism is often associated with

hypoprothrombinemia and this condition increases the risk of salicylate-induced bleeding. Patients should be warned

regarding the potential for increased risk of GI bleeding if alcohol-containing beverages are taken concurrently with

salicylates

Adderall (Amphetamine Aspartate) with Alcohol


Amphetamines do not change the pharmacokinetics of ethanol nor do they relieve cognitive impairment that results from

ethanol intoxication, even though subjective improvements in motor performance have been noted on concomitant ingestion

by patients. Ethanol containing beverages generally should be avoided.

BuSpar (Buspirone) with Alcohol


• warn against driving or operating machinery or performing other hazardous tasks until drug effects are known

• monitor for an increase in CNS/respiratory depression

Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS

depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS

depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use

of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower

dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.

DUTOPROL (Metoprolol Succinate) effectiveness may be reduced due to aggravation of underlying condition by Adderall(Amphetamine Aspartate)


• consider alternative drug therapy

• monitor for altered clinical response to drug therapy

• monitor blood pressure

Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive

agents. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.

Adderall (Amphetamine Aspartate) aggravate underlying condition, thus reducing effectiveness of Delone, Lasix(Furosemide)



• monitor heart rate

Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive

agents, such as loop diuretics.






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DUTOPROL (Metoprolol Succinate) may have a mutually antagonistic effect with Adderall (Amphetamine Aspartate)




Concurrent use of beta-blocking agents with sympathomimetics can result in mutual antagonism of desired therapeutic

effects of either agent and/or can cause unopposed alpha pharmacodynamic effects.

Coumadin, Jantoven (Warfarin) causes additive effects that may result in increased risk of bleeding with Aspirin


• monitor for evidence of bleeding

Co-use may increased the risk of bleeding.

Beers criteriaAnticholinergic burdenADRDrug InteractionLifestyleGeneticModerate Risks

Delone, Lasix (Furosemide) with Alcohol



Ethanol, since it also possesses diuretic properties, should be taken in small quantities in patients receiving loop diuretics. The

diuretic properties may be additive, leading to dehydration in some patients. In addition, ethanol has hypotensive properties

which can enhance the antihypertensive effects of diuretics.

Coumadin, Jantoven (Warfarin) with Alcohol

• monitor for evidence of bleeding

• monitor international normalized ratio (INR) or prothrombin time

In controlled studies of patients or healthy subjects anticoagulated with warfarin, small to moderate amounts of wine do not

alter INR values or warfarin levels. However, acute intoxication resulting from large amounts of ethanol may enhance the

hypoprothrombinemic response to oral anticoagulants due to inhibition of warfarin's metabolism.

DUTOPROL (Metoprolol Succinate) with Alcohol


Ethanol interacts with antihypertensive agents by potentiating their hypotensive effect.

Kazano (Alogliptin) with Alcohol








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Alcohol (ethanol) may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Alcohol

ingestion can decrease endogenous glucose production potentiating the risk of hypoglycemia. Alternatively, alcohol can

worsen glycemic control as it provides a source of additional calories. In addition, blood lactate concentrations and the lactate

to pyruvate ratio increase when metformin is coadministered with ethanol. Elevated lactic acid concentrations are associated

with increased morbidity rates. Ethanol should be avoided, if possible, in patients taking metformin. Many non-prescription

drug products may be formulated with ethanol; have patients scrutinize product labels prior to consumption. • Alcohol

(ethanol) may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Alcohol

ingestion can decrease endogenous glucose production potentiating the risk of hypoglycemia. Alternatively, alcohol can

worsen glycemic control as it provides a source of additional calories. Blood glucose concentrations should be closely

monitored and dosage adjustments of antidiabetic agents may be necessary if alcohol is consumed. Patients should be

encouraged to limit or moderate their intake of alcoholic beverages. Because of its effects on endogenous glucose production,

patients should be encouraged to avoid alcohol ingestion during the fasting state. Many non-prescription drug products may

be formulated with ethanol; have patients scrutinize product labels prior to consumption.

Genetic warning for Coumadin, Jantoven (Warfarin)

Individuals with this combination of alleles may benefit from an increased dose of Warfarin. The FDA table recommends a

therapeutic dose of 5-7 mg/day.

DUTOPROL (Metoprolol Succinate) may have their effect reduced by Aspirin



Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to

inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.

Kazano (Alogliptin) may increase risk of hypoglycemia with Aspirin



Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease

blood glucose concentrations. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents.

DUTOPROL (Metoprolol Succinate) may have an unpredictable effect with Aspirin


Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin

synthesis, which can lead to fluid retention and increased peripheral vascular resistance.

Kazano (Alogliptin) alters the pharmacodynamic parameters of DUTOPROL (Metoprolol Succinate)








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Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Because of this,

a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents.

Kazano (Alogliptin) has its effect increased by Adderall (Amphetamine Aspartate)



Amphetamines may potentiate the actions of some antidiabetic agents. As long as blood glucose is carefully monitored to

avoid hypoglycemia, it appears that amphetamines can be used concurrently.

DUTOPROL (Metoprolol Succinate) may have an additive effect with Delone, Lasix (Furosemide)

• monitor renal function


• monitor heart rate

• monitor serum potassium

• monitor serum electrolytes

Use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and

monitor the clinical response for the condition treated.

Kazano (Alogliptin) has its pharmacodynamic parameters altered by Aspirin



Large doses of salicylates may enhance hypoglycemia in diabetic patients. If these agents are administered or discontinued in

patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control.

Aspirin may reduce effect of Delone, Lasix (Furosemide)



• monitor patient clinically

Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of

renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored.




Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia.Diuretic-induced

hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists. Monitor

closely.






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Kazano (Alogliptin) effectiveness may be reduced due to aggravation of underlying condition by Adderall (AmphetamineAspartate)



Patients receiving alogliptin should be closely monitored for loss of diabetic control when therapy with sympathomimetic

agents is instituted.





Beta-blockers can prolong hypoglycemia by interfering with the mobilization of glycogen stores or can promote

hyperglycemia. Also, beta-blockers can blunt some of the physiologic symptoms of hypoglycemia, such as tremors and

tachycardia.

Beers criteriaAnticholinergic burdenADRDrug InteractionLifestyleGeneticMinor Risks

Kazano (Alogliptin) has its effect reduced by Delone, Lasix (Furosemide)




Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced

hypokalemia.

DUTOPROL (Metoprolol Succinate) has an unpredictable effect with Coumadin, Jantoven (Warfarin)



Per the prescribing information for warfarin sodium (Coumadin), use of diuretics (e.g., hydrochlorothiazide) with warfarin

may increase or decrease PT/INR response. Monitor accordingly with drug initation, adjustment, or discontinuation.

Coumadin, Jantoven (Warfarin) has an unpredictable effect with Delone, Lasix (Furosemide)



Per the prescribing information for warfarin sodium (Coumadin), the use of diuretics (e.g., furosemide) with warfarin is

associated with increases and decreases in PT/INR response. Monitor accordingly with drug initation, adjustment, or

discontinuation.






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Kazano (Alogliptin) has its effect reduced by Delone, Lasix (Furosemide)



Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. Because of this, a potential

pharmacodynamic interaction exists between furosemide and all antidiabetic agents, including alogliptin.

BuSpar (Buspirone) may have its serum concentration increased by Aspirin


• monitor for signs of drug toxicity

In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23%

through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed.

DUTOPROL (Metoprolol Succinate) increases effect of Coumadin, Jantoven (Warfarin)



Concomitant use of beta-blockers and warfarin may result in elevations in PT/INR response; patients receiving warfarin

should be monitored for changes in the INR when beta-blockers are initiated or discontinued, or if the dosage is changed.






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Thrombosis Profile

Tested Genes (Alleles) Genotype Predicted Phenotype Clinical Guidance

Prothrombin (F2) Normal

Factor V Leiden Normal

MTHFR (A1298C) Normal

MTHFR (C677T) Homozygous

variant

Normal risk expected based on the

patient’s genotype.

The absence of these variant alleles of

Prothrombin (Factor II) and Factor V

Leiden suggests that the patient does not

have the elevated risk of thrombosis

associated with these genetic markers.

General Description

Genetic analyses of three genes (four alleles) considered to increase the risk for venous thrombosis were performed using molecular genetic

techniques. The presence of the Prothrombin (Factor 2) gene allele 20210A and Factor V Leiden allele 1691A are risk factors for venous

thrombosis. This risk may be further increased by the use of estrogen therapy, oral contraceptives, pregnancy, and surgery.

Patients who are homozygous for MTHFR 677T or MTHFR 1298C may have a further increased risk for venous thrombosis if they also possess

the Factor V Leiden 1691A allele. However the MTHFR alleles alone do not predict a significant risk for venous thrombosis.

References and Useful Information:

• Factor V Leiden Working Group; ACMG Laboratory Quality Assurance Molecular Subcommittee of the ACMG Laboratory Quality Assurance

Committee AMERICAN COLLEGE OF MEDICAL GENETICS; Standards and Guidelines for Clinical Genetics Laboratories; 2006 Edition

◦ Middeldorp S, Henkens CM, Koopman MM, van Pampus ECM,Hamulyák K, van der Meer J, Prins MH, Büller HR. The incidence of venous

thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med 1998;128:15-20.

◦ Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral contraceptive users

who are carriers of factor V Leiden mutation. Lancet 1994;344:1453-1457.

◦ Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for factor V Leiden (activated

protein C resistance). Blood 1995;85(6):1504-1508.

◦ Reich LM, Bower M, Key NS. Role of the geneticist in testing and counseling for inherited thrombophilia. Genet Med 2003;5:133-143.

◦ Tosetto A, Rodeghiero F, Martinelli I, De Stefano V, Missiaglia E, Chiusolo P, Mannucci PM. Additional genetic risk factors for venous

thromboembolism in carriers of the factor V Leiden mutation. Br J Haematol 1998;103:871-876.

◦ De Stefano V, Martinelli I, Mannucci PM, Paciaroni K, Chiusolo P, Casorelli I, Rossi E, Leone G. The risk of recurrent deep venous thrombosis

among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999;341:801-806.

• M. Adams, P.D. Smith, D. Martin, J.R. Thompson, D. Lodwick, N.J. Samani. Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk

factor for myocardial infarction. QJM. 1996 Jun;89(6):437-44.






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ApoE Genotype Information†

Tested Genes (Alleles) Genotype Predicted Phenotype Clinical Guidance

ApoE (ɛ2, ɛ3, ɛ4) ɛ3|ɛ3 Often associated with normal lipid

metabolism.

Typical cardiovascular disease risk

expected.

General Description

Genetic analysis in the ApoE gene was performed using molecular genetic techniques. The genotype is based on genotyping results for this

patient at SNPs rs429358 and rs7412.

ApoE ɛ3 is the most common allele—found in about 60% of people. The presence of ɛ2 or ɛ4 alleles may be a risk factor for multiple conditions

including cardiovascular disease. ApoE ɛ2 carriers may be more likely to develop familial dysbetalipoproteinemia or type III

hyperlipoproteinemia.

† Predicted phenotype, clinical significance, relative risk, and interpretations reported for each genotype are associated with cardiovascular risk

only. The interpretations should not be used to determine the relative risk of other diseases. Other factors important to understanding total risk

should be considered.






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Medication Summary (more alternatives discoverable at GeneDose™ LIVE)Secured URL: https://app.genedose.com/?token=dXXHXXF54

Cardiac

Therapeutic Class Standard Precautions Caution / Info Change recommended

Antiarrhythmics Flecainide

Propafenone

Anticoagulants Acenocoumarol Warfarin

Anticonvulsants Phenytoin

Antiplatelet Agents Clopidogrel Ticagrelor

Beta Blockers Carvedilol Metoprolol

Statins Atorvastatin

Simvastatin

Gastroenterology


Antidepressants Mirtazapine

Trazodone

Amitriptyline

Clomipramine

Desipramine

Doxepin

Nortriptyline

Immunosuppressants Cyclosporine

Nonsteroidal Anti-

Inflamatory Drugs

(NSAIDs)

Celecoxib

Proton Pump

Inhibitors (PPIs)

Dexlansoprazole

Esomeprazole

Lansoprazole

Omeprazole

Pantoprazole

Rabeprazole

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Citalopram / Escitalopram Paroxetine






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Infectious Disease


Antifungals Ketoconazole

Voriconazole

Pain


Anticonvulsants Clobazam

Phenytoin

Antidepressants Duloxetine

Flupenthixol

Mirtazapine

Moclobemide

Trazodone

Amitriptyline

Clomipramine

Desipramine

Doxepin

Nortriptyline

Protriptyline

Venlafaxine

Vortioxetine

Antipsychotics Olanzapine

Immunosuppressants Cyclosporine Tacrolimus

Muscle Relaxants Carisoprodol

Nonsteroidal Anti-

Inflamatory Drugs

(NSAIDs)

Celecoxib

Diclofenac

Flurbiprofen

Meloxicam

Opioids Buprenorphine Codeine

Oxycodone

Tramadol

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Citalopram / Escitalopram

Sertraline

Fluoxetine

Paroxetine






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Psychotropic


Anti-ADHD Agents Atomoxetine

Anticonvulsants Clobazam

Phenytoin

Antidementia

Agents

Donepezil

Antidepressants Duloxetine

Flupenthixol

Mirtazapine

Moclobemide

Trazodone

Amitriptyline

Clomipramine

Desipramine

Doxepin

Nortriptyline

Protriptyline

Venlafaxine

Vortioxetine

Antipsychotics Clozapine

Haloperidol

Olanzapine

Quetiapine

Aripiprazole

Risperidone

Zuclopenthixol

Thioridazine

Anxiolytics Alprazolam

Buspirone

Clonazepam

Hypnotics Eszopiclone

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Citalopram / Escitalopram

Sertraline

Fluoxetine

Paroxetine

Other Drugs


Antidiabetics Glibenclamide

Gliclazide

Glimepiride

Saxagliptin

Tolbutamide

Cholinergic Agonists Cevimeline

Contraceptives Estrogen-containing oral

contraceptives

Immunosuppressants Sirolimus






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Legend Clinical Evidence Level

Typical response is expected Additional information available Strong

Change recommended Response is uncertain Moderate

Consider alternative therapy Emerging

Medication Report Details (by therapeutic class)

Drug Finding Recommendation Concern Evidence Reference

Anti-ADHD Agents

Atomoxetine

(Strattera)

CYP2D6: Intermediate

metabolizer. One allele

showing reduced activity and

one showing little or no

activity.

Typical response is expected; no additional

therapeutic recommendations.

8, 22

Antiarrhythmics

Flecainide

(Tambocor)





activity.

Individuals with intermediate metabolizer

status have the potential for decreased

elimination. Consider reducing dose by

25%; record ECG; monitor plasma

concentration.

ADR 8

Propafenone

(Rythmol)





activity.


status have decreased metabolism to less

active compounds; the resultant increased

plasma concentrations may increase the

risk proarrhythmia, exaggerated beta-

adrenergic blocking activity, and other

adverse events. Adjust dose in response to

plasma concentration and record ECG or

select alternative drug (e.g. sotalol,

disopyramide, quinidine, amiodarone).

ADR 8, 27

Anticoagulants

Acenocoumarol

(Sintrom, Acitrom)

CYP2C9: Extensive

metabolizer. Two alleles

showing normal activity.



8

Warfarin

(Coumadin)

Multigenic:

VKORC1, CYP2C9:

Two alleles showing normal

activity.; Extensive



Individuals with this combination of alleles

may benefit from an increased dose of

Warfarin. The FDA table recommends a

therapeutic dose of 5-7 mg/day.

74






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Anticonvulsants

Clobazam

(Onfi)

CYP2C19: Extensive





37

Phenytoin

(Dilantin)

CYP2C9: Extensive





8

Antidementia Agents

Donepezil CYP2D6: Intermediate




activity.



38






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Antidepressants

Amitriptyline

(Elavil)





activity.


status have reduced metabolism of

amitriptyline to less active compounds; the

resultant higher plasma concentrations will

increase the probability of side effects.

Consider reducing the recommended

starting dose by 25% and monitor plasma

concentration or select alternative drug

(e.g. citalopram, sertraline).

ADR 8, 26

Clomipramine

(Anafranil)





activity.


status have reduced metabolism to less

active compounds; the resultant higher


probability of side effects. Insufficient

evidence to allow calculation of dose

adjustment. Monitor (desmethyl)

clomipramine plasma concentration.

ADR 8

Desipramine

(Norpramin)





activity.


status have reduced metabolism of tricyclic

antidepressants; the resultant higher


probability of side effects. Monitor plasma

concentration or select alternative drug.

ADR 26

Doxepin

(Deptran)





activity.


status have reduced metabolism to less

active compounds. Higher plasma

concentrations will increase the probability

of side effects. Reduce dose by 20%. Adjust

maintenance dose in response to

(nor)doxepin plasma concentration.

ADR 8

Duloxetine

(Cymbalta)





activity.



8, 25

Flupenthixol CYP2D6: Intermediate




activity.



8






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Imipramine

(Tofranil)

Multigenic:

CYP2C19, CYP2D6:

Extensive metabolizer. Two

alleles showing normal

activity. Intermediate




activity.

Multiple results from uncorrelated genes.

CYP2C19: Typical response is expected; no

additional therapeutic recommendations.

CYP2D6: Recommended dosage

adjustment and additional monitoring

suggested

8

Mirtazapine CYP2D6: Intermediate




activity.



8

Moclobemide CYP2C19: Extensive





8

Nortriptyline

(Pamelor)





activity.


status have reduced metabolism of

tricyclics to less active compounds when

compared to extensive metabolizers; the

resultant higher plasma concentrations will

increase the probability of side effects.

Consider reducing the dose by 40% and

monitor nortriptyline

10-hydroxynortriptyline plasma

concentrations.

ADR 8, 26

Protriptyline

(Vivactil)





activity.


status have reduced metabolism of tricyclic

antidepressants; the resultant higher


probability of side effects. Monitor plasma

concentration or select alternative drug.

ADR 52

Trazodone

(Oleptro, Desyrel)

CYP3A4: Extensive





67

Venlafaxine

(Effexor)





activity.

Insufficient evidence to allow calculation of

dose adjustment. Consider selecting

alternative drug (e.g. citalopram, sertraline)

or adjust dose to clinical response and

monitor (O-desmethyl) venlafaxine plasma

concentration.

8






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Vortioxetine

(Brintellix)





activity.


status may be at an increased risk of

adverse drug reactions due to reduced

metabolic clearance and high plasma

concentrations of the active compound.

Consider reducing the dose.

ADR 73

Antidiabetics

Glibenclamide

(Glyburide)

CYP2C9: Extensive





8

Gliclazide CYP2C9: Extensive





8

Glimepiride CYP2C9: Extensive





8

Saxagliptin

(Onglyza)

CYP3A4: Extensive





71

Tolbutamide

(Orinase)

CYP2C9: Extensive





8

Antifungals

Ketoconazole

(Nizoral)

CYP3A4: Extensive





72

Voriconazole CYP2C19: Extensive





8, 21

Antiplatelet Agents

Clopidogrel

(Plavix)

CYP2C19: Extensive





8

Ticagrelor

(Brilinta)

CYP3A4: Extensive





ADR &

Efficacy

51






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Antipsychotics

Aripiprazole

(Abilify)





activity.

Intermediate metabolizers are at uncertain

risk of adverse drug reaction. However,

note that for individuals with poor

metabolizer status it is recommended to

reduce the maximum dose to 10 mg/day

(67% of the maximum recommended daily

dose).

ADR 8, 58

Clozapine CYP2D6: Intermediate




activity.



8, 24

Haloperidol

(Haldol)





activity.



8

Olanzapine

(Zalasta, Zyprexa)





activity.



8

Quetiapine

(Seroquel)

CYP3A4: Extensive





61

Risperidone

(Risperdal)





activity.


dose adjustment. Consider selecting

alternative drug (e.g. quetiapine,

olanzapine, clozapine) or being extra alert

to adverse drug events and adjusting dose

to clinical response.

ADR 8, 28

Thioridazine CYP2D6: Intermediate




activity.


status are at an increased risk of serious

adverse drug reactions due to elevated

levels of thioridazine. Select alternative

drug.

ADR 35






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Zuclopenthixol CYP2D6: Intermediate




activity.

Individuals with poor metabolizer status

have decreased metabolism to less active

compounds; the resultant increased plasma

concentrations may increase the risk of

adverse drug reactions. Reduce the

standard dose by 25% or select an

alternative drug (flupenthixol, quetiapine,

olanzapine, clozapine).

ADR 8

Anxiolytics

Alprazolam

(Xanax, Niravam)

CYP3A4: Extensive





68

Buspirone

(Buspar)

CYP3A4: Extensive





69

Clonazepam

(Klonopin)

CYP3A4: Extensive





70

Beta Blockers

Carvedilol

(Coreg)





activity.



8, 23

Metoprolol

(Lopressor)





activity.


status have increased risk of adverse drug

reactions. For heart failure (indication):

select alternative drug (e.g. bisoprolol,

carvedilol) or reduce dose by 50%. For

other indications: be alert to adverse drug

events (e.g. bradycardia, cold extremities)

or select alternative drug (e.g. atenolol,

bisoprolol).

ADR 8






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Cholinergic Agonists

Cevimeline

(Evoxac)





activity.


status may be at an increased risk of

adverse drug reactions due to reduced

metabolic clearance and abnormally high

plasma concentrations of the active

compound. Insufficient evidence to allow

calculation of dose adjustment. Cevimeline

should be administered with caution.

ADR 60

Contraceptives

Estrogen-

containing oral

contraceptives

F5: Two wild-type alleles. Typical response is expected; no additional


8

Hypnotics

Eszopiclone

(Lunesta)

CYP3A4: Extensive





66

Immunosuppressants

Cyclosporine

(Gengraf, Neoral)

CYP3A4: Extensive





63

Sirolimus

(Rapamune)

CYP3A4: Extensive





64

Tacrolimus

(Prograf, Hecoria)

CYP3A5: *3|*3 Individuals with poor metabolizer status

have higher dose-adjusted trough

concentrations of tacrolimus; the resultant

increased concentrations may increase the

probability of pharmacotherapy success.

Consider initiating therapy with the

recommended starting dose. In liver

transplant patients, donor genotype should

be considered as well as the recipient's.

76

Muscle Relaxants

Carisoprodol

(Soma)

CYP2C19: Extensive





33, 78






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Non-drug

ApoE ApoE: Often associated with

normal lipid metabolism.

Typical cardiovascular disease risk

expected.

Nonsteroidal Anti-Inflamatory Drugs (NSAIDs)

Celecoxib

(Celebrex)

CYP2C9: Extensive





1, 19

Diclofenac

(Cataflam)

CYP2C9:rs1057910: Two

alleles showing normal

activity.



29

Flurbiprofen

(Ocufen)

CYP2C9: Extensive





30

Meloxicam

(Mobic)

CYP2C9: Extensive





32






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Opioids

Buprenorphine

(Butrans,

Buprenex)

CYP3A4: Extensive





62

Codeine CYP2D6: Intermediate




activity.

For analgesia, select alternative drug (e.g.

acetaminophen, NSAID, morphine; not

tramadol or oxycodone) or be alert to

symptoms of insufficient pain relief. For

cough, there are no data on the effect of

CYP2D6 genotype or phenotype on the

antitussive effect of codeine.

Efficacy 8

Oxycodone

(Oxycontin)





activity.


status are at risk of potentially reduced

efficacy; consider alternative therapy.


dose adjustment. Select alternative drug

(not tramadol or codeine) or be alert to

symptoms of insufficient pain relief.

Efficacy 8

Tramadol

(Ultracet, Ultram)





activity.


status have decreased metabolism to more

active compounds; the resultant decreased


probability of pharmacotherapy failure.

Consider dose increase. If response is still

inadequate; select alternative drug (not

oxycodone or codeine) or be alert to

symptoms of insufficient pain relief.

Efficacy 8






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Proton Pump Inhibitors (PPIs)

Dexlansoprazole

(Kapidex,

Dexilant)

CYP2C19: Extensive





11

Esomeprazole

(Nexium)

CYP2C19: Extensive





12

Lansoprazole

(Prevacid)

CYP2C19: Extensive





5

Omeprazole

(Prilosec, Zegerid)

CYP2C19: Extensive





4

Pantoprazole

(Protonix)

CYP2C19: Extensive





6

Rabeprazole

(Aciphex)

CYP2C19: Extensive





7






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Selective Serotonin Reuptake Inhibitors (SSRIs)

Citalopram /

Escitalopram

(Celexa, Lexapro)

CYP2C19: Extensive





8, 20

Fluoxetine

(Prozac)





activity.

Individuals taking fluoxetine should be alert

to concomitant use of drugs metabolized by

CYP2D6. For a more in-depth

recommendation for individuals taking

fluoxetine, please visit this individual's

GeneDose Live profile. Briefly, fluoxetine is

a potent inhibitor of CYP2D6 enzyme

pathway. Fluoxetine inhibits the activity of

CYP2D6, and may make individuals with

normal CYP2D6 metabolic activity

resemble a poor metabolizer.

Coadministration of fluoxetine with other

drugs that are metabolized by CYP2D6,

including certain antidepressants (e.g.

TCAs), antipsychotics (e.g. phenothiazines

and most atypicals), and antiarrhythmics

(e.g. propafenone, flecainide, and others)

should be approached with caution.

ADR &

Efficacy

39

Paroxetine

(Paxil)





activity.


status may have increased plasma

concentrations/ decreased clearance of

paroxetine. However, an association with

treatment response or severity of side

effects is not conclusive.

ADR 8

Sertraline

(Zoloft)

CYP2C19: Extensive





8

Statins

Atorvastatin

(Lipitor, Caduet)

CYP3A4: Extensive





54, 55

Simvastatin

(Zocor)

SLCO1B1: Normal liver

uptake activity.

Individuals with normal SLCO1B1 liver

uptake activity are expected to have a

typical response to a standard dose of

simvastatin.

3






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References

Available at GeneDose.com or by request.

Clinical Evidence Levels

Strong

• Includes gene-drug pairs approved by the Coriell Institute for Medical Research Pharmacogenomics Advisory Group.

• Includes gene-drug pairs supported by multiple studies documenting consistent effects of specific genetic variant(s) on clinical outcomes.

• Includes gene-drug pairs approved by the Dutch Pharmacogenetics Working Group (DPWG) and/or guidelines published in Clinical Pharmacology and

Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Moderate

• Includes gene-drug pairs supported by pharmacokinetic, pharmacodynamic, or molecular/cellular functional studies showing consistent effects of

genetic variant(s).

• Includes Drug product information (e.g. This interpretation is based on guidance available in the FDA (Food and Drug Administration) drug label for

ABILIFY® (10/2013).

• Includes gene-drug pairs for which potential clinical outcomes are inferred from similar gene-drug interactions approved by the Dutch

Pharmacogenetics Working Group (DPWG), and/or guidelines published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics

Implementation Consortium (CPIC), and/or pharmacogenomic reports and submission from the Coriell Institute for Medical Research.

Emerging

• Includes gene-drug pairs supported by published studies of the drug, related drug, or a probing compound of interest involving limited data and/or

inconsistent findings.






Page 27 of 28

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Patient Information Card

This card contains an abbreviated genetic summary.

It is not intended as a replacement for the complete GeneDose™ report.

Personalized Genetic Testing

www.pgenetic.com

Patient: Doe, John

DOB: Sample ID: GeneDose Key:

1955-01-01 1000.99999 N/A

Pharmacogenomic Summary

ApoE ɛ3|ɛ3 See full GeneDose report

Factor V Leiden Normal See full GeneDose report

MTHFR (A1298C) Normal See full GeneDose report

MTHFR (C677T) Variant See full GeneDose report

Prothrombin (F2) Normal See full GeneDose report



CYP2D6 *5|*41 Intermediate metabolizer

CYP3A4 *1A|*1A Extensive metabolizer

CYP3A5 *3|*3 Poor metabolizer

SLCO1B1 *1|*1 Normal liver uptake activity

VKORC1 *1|*1 Normal (with respect to Warfarin)

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