genedose genetic response report · ispm labs d/b/a capstone diagnostics 8601 dunwoody pl, ste 444...

ISPM Labs d/b/a Capstone Diagnostics8601 Dunwoody Pl, Ste 444 • Atlanta GA 30350 Phone: (678) 515-4524 • Fax: (470) 355-5462 Laboratory Director: John Hanson, PhDCLIA ID Number: 11D2073885http://www.capstonediagnostics.com

This report combines (i) an analysis of the patient’s DNA by ISPM Labs d/b/a Capstone Diagnostics, identifying relevant genetic variants that are informative

for medication efficacy, safety, and dosing, with (ii) an interpretation of the identified DNA variants by Coriell Life Sciences to bring you immediately

actionable clinical guidance regarding safer and more effective medications and dosages for the patient.

P atient: Doe, Jane

Date of Birth: Jan 01, 1990

Gender: F emale

Ph ysician: Dr . Example

Pr actice: Example Health Associates

Specimen type: Buccal swab

Sample ID: e x222

GeneDose Live

Individualized, additional therapeutic decision support

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

indications, demographics, and lifestyle indicators are

available at GeneDose Live via this secured URL:

https://alpha.genedose.com?token=prompt

GeneDose Key: ACAZPCM6PSample ID: ex222

Table of Contents

Genetic Summary Information

Pg. 1Genetic Summary

Pg. 3Current Regimen Risk Chart

Pg. 4Current Regimen Risk Detail (by severity)

Pg. 6Thrombosis Profile

Pg. 7ApoE Genotype Information

Pg. 8Medications Summary

Pg. 11Medication Report Details (by therapeutic class)

Pg. 26References

Pg. 27Patient Information Card

AppendixSNP Report

† When multiple activities are listed, check information in MedicationReport Details (Pg. 11) for specific medication of interest.Uncertain = No known diplotype/result (name) or activity for thiscombination of genetic variants; Uninterpretable Genotype.

Genetic Summary

Gene Result Activity †

ApoE ɛ3|ɛ3 See ApoE Genotype Info.

CYP2C19 *8|*8 Poor metabolizer

CYP2C9 *1|*1 Extensive metabolizer

CYP2D6 *1|*1x2 Ultrarapid metabolizer

CYP3A4 *1B|*1B Ultrarapid metabolizer

CYP3A5 *1A|*1A; or*1A|*1D; or

Extensive metabolizer

6P C|C n/a

Factor V Leiden Variant See thrombosis profile

HLA-B*1502 WT|WT WT

MTHFR (A1298C) Variant See thrombosis profile

MTHFR (C677T) Variant See thrombosis profile

Prothrombin (F2) Normal See thrombosis profile

K1 A|T Altered Activity

K C|C Normal Activity

T 2A

GeneDose Genetic Response Report

ex222 - Doe, Jane - Reported Mar 21, 2017 - DRAFT Powered by:

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.

of 26

ANKK1 *8|*8 Poor metabolizer

ATM *8|*8 Poor metabolizer

ABCB1 *1|*36 Altered Activity

CYP1A2 *8|*8 Uncertain

CYP2B6 *8|*8 Poor metabolizer

C|C Normal Activity

https://alpha.genedose.com/?token=ACAZPCM6P

Current Regimen Risk Chart

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

Genetic Drug interaction Anticholinergic burden LifestyleADR (Black box)

Epitol, Tegretol (Carbam…

Codeine

Zoloft (Sertraline)

BRIVIACT (Brivaracetam)

Folicet (Folic Acid)

Absorica, Accutane, Am…

0 5 10 15 20 25 30 35

This chart summarizes the various risk factors associated with each medication entered into GeneDose™ Live for Jane Doe. The length of each colored segment

represents the relative contribution of a risk category (detailed in the below legend) to the overall risk associated with the use of a medication. For further

information, consult the Current Regimen Risk Details Pg. 3 section.

For further assistance in choosing alternative medications to reduce this patient’s risk, use the modeling tool at https://alpha.genedose.com?token=prompt.






Page 2 of 26


Current Regimen Risk Detail

Severe Risks

Strong regimen anticholinergic burden

Major Risks

Genetic warning for Zoloft (Sertraline)

Genetic warning for Codeine

BRIVIACT (Brivaracetam) has its effect decreased by, and increases effect of Epitol, Tegretol (Carbamazepine)

• monitor for signs of drug toxicity

• monitor for altered clinical response to drug therapy

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

• dosage reduction may be required

Moderate Risks

Epitol, Tegretol (Carbamazepine) may decrease concentration of Codeine

• use combination with caution

• monitor for altered clinical response to drug therapy

• adjust drug dosage

Epitol, Tegretol (Carbamazepine) reduces effect of Zoloft (Sertraline)


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.

Individuals with poor metabolizer status may have higher plasma concentrations and decreased clearance. Reduce dose by

50%.

For analgesia, select alternative drug (e.g. acetaminophen, NSAID, morphine; not tramadol or oxycodone). Be extra alert to

adverse drug events due to increased morphine plasma concentration.

Coadministration with carbamazepine may increase exposure to the active metabolite of carbamazepine, carbamazepine-

epoxide. A 26% decrease in the plasma concentration of brivaracetam has also been observed during co-administration.

Inducers of CYP3A4 such as carbamazepine, may induce the hepatic metabolism of opiate agonists, which may lead to opiate

withdrawal or inadequate pain control. Clinicians should be alert to changes in the effect of the opioid agonist.






Page 3 of 26

• monitor patient clinically

Minor Risks

Codeine has its effect reduced by Zoloft (Sertraline)


• monitor patient clinically

Sertraline is a substrate for CYP3A4 and CYP2C19. Drugs that induce hepatic isoenzymes, such as carbamazepine could

decrease sertraline plasma concentrations, potentially causing decreased effectiveness of sertraline.

The activity of codeine is due to its conversion to morphine via the cytochrome P450 CYP2D6 hepatic isoenzyme. The

analgesic activity of codeinemay be reduced when it is combined with drugs that inhibit CYP2D6, such as sertraline.






Page 4 of 26

Thrombosis Profile

Tested Genes (Alleles) Genotype Predicted Phenotype Clinical Guidance

Prothrombin (F2) Normal

Factor V Leiden Homozygous

variant

MTHFR (A1298C) Homozygous

variant

MTHFR (C677T) Homozygous

variant

Variant alleles detected. It is

important for individuals

possessing this allelic variant

to understand the clinical

risks and the genetic

implications of their result.

Patients should be

counseled by their physician

or genetic counselor

Individuals homozygous for the Factor V Leiden

mutation have an approximately 80-fold increased

risk of venous thrombosis as compared to

individuals without the mutation. Patients who

are homozygous for either MTHFR variant may

have a further increased risk for venous

thrombosis if they also possess the Factor V

Leiden 1691A allele.

General Description

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.

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.






Page 5 of 26

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.






Page 6 of 26

Medication Summary (more alternatives discoverable at GeneDose Live)Secured URL: https://alpha.genedose.com/?token=ACAZPCM6P

Cardiac

Therapeutic Class Standard Precautions Caution / Info Change recommended

Antiarrhythmics

Anticoagulants

Anticonvulsants

Antiplatelet Agents

Beta Blockers

Statins

Gastroenterology


Antidepressants

Immunosuppressants

Nonsteroidal Anti-

Inflamatory Drugs

(NSAIDs)

Proton Pump

Inhibitors (PPIs)

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Flecainide

Propafenone

Acenocoumarol Warfarin

Phenytoin

Ticagrelor Clopidogrel

Carvedilol Metoprolol

Simvastatin Atorvastatin

Mirtazapine Amitriptyline

Clomipramine

Desipramine

Doxepin

Nortriptyline

Trazodone

Azathioprine

Mercaptopurine

Thioguanine

Cyclosporine

Celecoxib

Dexlansoprazole

Esomeprazole

Lansoprazole

Omeprazole

Pantoprazole

Rabeprazole

Citalopram

Paroxetine






Page 7 of 26


Infectious Disease


Antifungals

Pain


Anticonvulsants

Antidepressants

Antipsychotics

Immunosuppressants

Muscle Relaxants

Nonsteroidal Anti-

Inflamatory Drugs

(NSAIDs)

Opioids

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Psychotropic


Anti-ADHD Agents

Anticonvulsants

Voriconazole Ketoconazole

Carbamazepine

Phenytoin

Clobazam

Duloxetine

Flupenthixol

Mirtazapine

Moclobemide

Amitriptyline

Clomipramine

Desipramine

Doxepin

Nortriptyline

Protriptyline

Trazodone

Venlafaxine

Vortioxetine

Olanzapine

Azathioprine

Mercaptopurine

Cyclosporine

Tacrolimus

Carisoprodol

Celecoxib

Diclofenac

Flurbiprofen

Meloxicam

Oxycodone (CYP3A5) Buprenorphine

Codeine

Oxycodone

Tramadol

Citalopram

Fluoxetine

Paroxetine

Sertraline

Atomoxetine

Carbamazepine

Phenytoin

Clobazam






Page 8 of 26

Psychotropic


Antidementia

Agents

Antidepressants

Antipsychotics

Anxiolytics

Hypnotics

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Other Drugs


Anticoagulants

Antidiabetics

Cholinergic Agonists

Immunosuppressants

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

Donepezil

Duloxetine

Flupenthixol

Mirtazapine

Moclobemide

Amitriptyline

Clomipramine

Desipramine

Doxepin

Nortriptyline

Protriptyline

Trazodone

Venlafaxine

Vortioxetine

Aripiprazole

Clozapine

Olanzapine

Haloperidol

Quetiapine

Risperidone

Thioridazine

Zuclopenthixol

Alprazolam

Buspirone

Clonazepam

Eszopiclone

Citalopram

Fluoxetine

Paroxetine

Sertraline

Warfarin

Glibenclamide

Gliclazide

Glimepiride

Tolbutamide

Saxagliptin

Cevimeline

Sirolimus

Escitalopram






Page 9 of 26

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

Anti-ADHD Agents

Atomoxetine

(Strattera)

CYP2D6: Ultrarapid

metabolizer. One allele

showing normal

activity and one

duplicated allele

showing increased

activity.

Individuals with ultrarapid metabolizer status have

increased metabolism; the resultant lower plasma

concentrations may increase the probability of

pharmacotherapy failure. However, there is insufficient

evidence to allow calculation of dose adjustment. Be alert

to reduced efficacy or select alternative drug (e.g.,

methylphenidate, clonidine).

Efficacy

Antiarrhythmics

Flecainide

(Tambocor)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Individuals with ultrarapid metabolizer status have the

potential for increased elimination. Record ECG and

monitor plasma concentration or select alternative drug

(e.g. sotalol, disopyramide, quinidine, amiodarone).

Efficacy

Propafenone

(Rythmol)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism to less active compounds; the

resultant decreased plasma concentrations may increase

the risk of pharmacotherapeutic failure. Insufficient

evidence to allow calculation of dose adjustment. Adjust

dose in response to plasma concentration and record ECG

or select alternative drug (e.g. sotalol; disopyramide;

quinidine; amiodarone).

Efficacy






Page 10 of 26


Anticoagulants

Acenocoumarol

(Sintrom, Acitrom)

CYP2C9: Extensive

metabolizer. Two

alleles showing normal

activity.

Typical response is expected; no additional therapeutic

recommendations.

Warfarin

(Coumadin)

Multigenic:

VKORC1, CYP2C9:

Two alleles showing

normal activity.;

Extensive metabolizer.

Two alleles showing

normal activity.

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.

Warfarin

(Coumadin)

Multigenic:

CYP2C9, VKORC1,

CYP4F2:

Extensive metabolizer.

Two alleles showing

normal activity.; Two


activity.; Normal

function. Two alleles

with normal activity.

Individuals with this combination of alleles may benefit

from a standard therapeutic dose of warfarin. Consider a

regimen of 4.1-5.9 mg/day (29-41 mg/week).

ADR &

Efficacy

Anticonvulsants

Carbamazepine

(Tegretol)

HLA-B*1502:

Negative; Absence of

*15:02 alleles.


recommendations. Individuals with no variant alleles

detected are at "normal" or reduced risk of

carbamazepine-associated cutaneous adverse reactions.

Clobazam

(Onfi)

CYP2C19: Poor

metabolizer. Two null

alleles showing

reduced activity.

Individuals with poor metabolizer status may be at an

increased risk of adverse drug reaction due to the

presence of higher concentrations of clobazam's active

metabolite. Consider reducing the initial dose. The FDA

approved labeling text for ONFI states that "For this

reason, the initial dose in patients known to be CYP2C19

poor metabolizers should be 5 mg/day. These patients

should be titrated initially to 10-20 mg/day, and may be

titrated further to a maximum daily dose of 40 mg if

tolerated."

ADR

Phenytoin

(Dilantin)

CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.






Page 11 of 26


Antidementia Agents

Donepezil CYP2D6: *1|*1x2 Typical response is expected; no additional therapeutic

recommendations.






Page 12 of 26


Antidepressants

Amitriptyline

(Elavil)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism of amitriptyline to less active

compounds; the resultant lower plasma concentrations will

increase the probability of pharmacotherapy failure. Select

an alternative drug or consider increasing the

recommended starting dose.

Efficacy

Clomipramine

(Anafranil)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.



resultant lower plasma concentrations may increase the

probability of pharmacotherapy failure. Select alternative

drug (e.g. citalopram; sertralin) or monitor (desmethyl)

clomipramine plasma concentration.

Efficacy

Desipramine

(Norpramin)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism of tricyclic antidepressants; the


probability of pharmacotherapy failure. Select an

alternative drug or consider increasing the recommended

starting dose.

Efficacy

Doxepin

(Deptran)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism to less active compounds. Lower

plasma concentrations will increase the probability of

pharmacotherapy failure. Select alternative drug

(citalopram, sertraline) or increase dose by 100%. Adjust

maintenance dose in response to (nor)doxepin plasma

concentration.

Efficacy

Duloxetine

(Cymbalta)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.

Flupenthixol CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.






Page 13 of 26


Imipramine

(Tofranil)

Multigenic:

CYP2C19, CYP2D6:

Poor metabolizer. Two

null alleles likely

showing little or no

activity. Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Multiple results from uncorrelated genes.

CYP2C19: Potential dosage adjustment or alternate drug

suggested CYP2D6: Consider alternative therapy

Mirtazapine CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.

Moclobemide CYP2C19: Poor


alleles likely showing

reduced activity.


recommendations.

Nortriptyline

(Pamelor)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism of tricyclics to less active

compounds when compared to extensive metabolizers; the

resultant lower plasma concentrations will increase

probability of pharmacotherapy failure. Consider

alternative therapy--select alternative drug (e.g.

citalopram, sertraline) or increase dose by 60% and

monitor nortriptyline 10-hydroxynortriptyline plasma

concentrations.

Efficacy

Protriptyline

(Vivactil)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism of tricyclic antidepressants; the


probability of pharmacotherapy failure. Select an

alternative drug or consider increasing the recommended

starting dose.

Efficacy

Trazodone

(Oleptro, Desyrel)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of trazodone; the resultant lower

plasma concentrations may increase the probability of

pharmacotherapy failure. Select an alternative drug or

monitor patient for a need to increase the dose.

Efficacy






Page 14 of 26


Venlafaxine

(Effexor)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Be alert to decreased venlafaxine and increased (O-

desmethyl) venlafaxine plasma concentration. Titrate dose

to a maximum of 150% of the normal dose or select

alternative drug (e.g. citalopram, sertraline).

Vortioxetine

(Brintellix)

CYP2D6: *1|*1x2 Individuals with ultrarapid metabolizer status have

increased clearance of vortioxetine; the resultant lower


pharmacotherapy failure. Consider increasing the dose.

Efficacy

Antidiabetics

Glibenclamide

(Glyburide)

CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.

Gliclazide CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.

Glimepiride CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.

Saxagliptin

(Onglyza)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of saxagliptin; the resultant lower



monitor patient for efficacy and adjust dose appropriately.

Efficacy

Tolbutamide

(Orinase)

CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.






Page 15 of 26


Antifungals

Ketoconazole

(Nizoral)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of ketoconazole; the resultant lower


pharmacotherapy failure. Ketoconazole is not

recommended.

Efficacy

Voriconazole CYP2C19: Poor



reduced activity.

Individuals with poor metabolizer status may have higher

voriconazole exposure. Adjust the dose and monitor for

adverse events or lack of efficacy.

ADR &

Efficacy

Antiplatelet Agents

Clopidogrel

(Plavix)

CYP2C19: Poor

metabolizer. Two

alleles showing

reduced activity.

Individuals with poor metabolizer status are at an

increased risk of therapeutic failure due to reduced

activation of the prodrug and low plasma concentrations of

the active compound. Clopidogrel is not recommended.

Efficacy

Ticagrelor

(Brilinta)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.

Individuals with ultrarapid metabolizer status may be at an

increased risk of adverse drug reactions and decreased

efficacy due to reduced metabolism of the prodrug to the

active metabolite. Insufficient evidence to allow

calculation of dose adjustment. Consider alternative drug.

ADR &

Efficacy






Page 16 of 26


Antipsychotics

Aripiprazole

(Abilify)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.

Clozapine CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.

Haloperidol

(Haldol)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.




the probability of pharmacotherapy failure. Insufficient

evidence to allow calculation of dose adjustment. Monitor

and adjust maintenance dose in response to haloperidol

plasma concentration or select alternative drug (e.g.

pimozide; flupenthixol; fluphenazine; quetiapine;

olanzapine; clozapine).

Efficacy

Olanzapine

(Zalasta, Zyprexa)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.

Quetiapine

(Seroquel)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased clearance of quetiapin; the resultant lower



consider increasing the recommended starting dose.

Efficacy

Risperidone

(Risperdal)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Insufficient evidence to allow calculation of dose

adjustment. Select alternative drug (e.g. quetiapine,

olanzapine, clozapine) or be extra alert to decreased

response and titrate dose in response to clinical effect and

adverse drug events.






Page 17 of 26


Thioridazine CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Individuals with ultrarapid metabolizer status may be at

risk of reduced efficacy due to increased metabolism of

thioridazine. Select an alternative drug or consider

increasing the recommended starting dose.

Efficacy

Zuclopenthixol CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.




the probability of pharmacotherapy failure. Insufficient

evidence to allow calculation of dose adjustment. Be alert

to low zuclopenthixol plasma concentrations or select

alternative drug (e.g. flupenthixol, quetiapine, olanzapine,

clozapine).

Efficacy

Anxiolytics

Alprazolam

(Xanax, Niravam)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of alprazolam; the resultant lower

plasma levels may increase the probability of



Efficacy

Buspirone

(Buspar)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of buspirone; the resultant lower

plasma levels may increase the probability of



Efficacy

Clonazepam

(Klonopin)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of clonazepam; the resultant lower



monitor patient for efficacy and adjust dose appropriately.

Efficacy






Page 18 of 26


Beta Blockers

Carvedilol

(Coreg)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


recommendations.

Metoprolol

(Lopressor)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism when compared to extensive

metabolizers; the resultant lower plasma concentrations

may increase probability of pharmacotherapy failure. For

heart failure (indication): select alternative drug (e.g.

bisoprolol, carvedilol) or titrate dose to a maximum of

250% of the normal dose in response to efficacy and

adverse drug events. For other indications: select

alternative drug (e.g. atenolol, bisoprolol) or titrate dose to

a maximum of 250% of the normal dose in response to

efficacy and adverse drug events.

ADR &

Efficacy

Cholinergic Agonists

Cevimeline

(Evoxac)

CYP2D6: *1|*1x2 Individuals with ultrarapid metabolizer status have

increased clearance of cevimeline; the resultant lower


pharmacotherapy failure. Insufficient evidence to allow

calculation of dose adjustment. Consider alternative drug.

Efficacy

Hypnotics

Eszopiclone

(Lunesta)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of eszopiclone; the resultant lower

blood concentrations may increase the probability of

pharmacotherapy failure. Consider selecting an alternative

drug.

Efficacy






Page 19 of 26


Immunosuppressants

Azathioprine

(Imuran)

TPMT: Extensive

metabolizer. Two


activity.

Individuals with extensive metabolizer status are expected

to have a typical response to thiopurines.

Cyclosporine

(Gengraf, Neoral)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of cyclosporine; the resultant lower



monitor circulating cyclosporine concentrations and adjust

dose appropriately.

Efficacy

Mercaptopurine

(Purinethol)

TPMT: Extensive

metabolizer. Two


activity.


to have a typical response to thiopurines.; no additional

therapeutic recommendations.

Sirolimus

(Rapamune)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.


increased metabolism of sirolimus; the resultant lower



monitor sirolimus trough concentrations and adjust dose

appropriately.

Efficacy

Tacrolimus

(Prograf, Hecoria)

CYP3A5: Two alleles

showing normal

activity.

Individuals with extensive metabolizer status have lower

dose-adjusted trough concentrations of tacrolimus; the

resultant decreased concentrations may increase the

probability of pharmacotherapy failure. Consider

increasing the recommended starting dose by 1.5 to 2

times (with a total starting dose not exceeding 0.3 mg/kg/

day). In liver transplant patients, donor genotype should be

considered as well as the recipient's.

Efficacy

Thioguanine

(6-TG, Tabloid, Lanvis)

TPMT: Extensive

metabolizer. Two


activity.


to have a typical response to thiopurines.

Muscle Relaxants

Carisoprodol

(Soma)

CYP2C19: Poor



reduced activity.

Individuals with poor metabolizer status may be at an

increased risk of adverse drug reactions due to reduced

carisoprodol metabolism. Carisoprodol should be

administered with caution.

ADR






Page 20 of 26


Non-drug

ApoE ApoE: Often

associated with normal

lipid metabolism.

Typical cardiovascular disease risk expected.

Nonsteroidal Anti-Inflamatory Drugs (NSAIDs)

Celecoxib

(Celebrex)

CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.

Diclofenac

(Cataflam)

CYP2C9:rs1057910:

Two alleles showing

normal activity.


recommendations.

Flurbiprofen

(Ocufen)

CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.

Meloxicam

(Mobic)

CYP2C9: Extensive

metabolizer. Two


activity.


recommendations.






Page 21 of 26


Opioids

Buprenorphine

(Butrans, Buprenex)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.

Individuals with ultrarapid metabolizer status may have

increased clearance of buprenorphine; the resultant lower


pharmacotherapy failure. It is recommended that patients

be monitored for signs and symptoms of opioid

withdrawal. Consider an alternative medication.

Efficacy

Codeine CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

For analgesia, select alternative drug (e.g. acetaminophen,

NSAID, morphine; not tramadol or oxycodone). Be extra

alert to adverse drug events due to increased morphine

plasma concentration.

ADR

Oxycodone

(Oxycontin)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Individuals with ultrarapid metabolizer status are at risk of

possible adverse drug reaction. Insufficient evidence to

allow calculation of dose adjustment. Select alternative

drug (not tramadol or codeine) or be alert to adverse drug

events (e.g. nausea; vomiting; constipation; respiratory

depression; confusion; urinary retention).

ADR

Oxycodone (CYP3A5)

(Oxycontin)

CYP3A5: Two alleles

showing normal

activity.


recommendations.

Tramadol

(Ultracet, Ultram)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.


increased metabolism to more active compounds; the

resultant increased plasma concentrations may increase

the probability of adverse drug reactions. Reduce dose by

30% and be alert to adverse drug events (e.g. nausea;

vomiting; constipation; respiratory depression; confusion;

urinary retention) or select alternative drug (e.g.

acetaminophen; NSAID; morphine - not oxycodone or

codeine).

ADR






Page 22 of 26


Proton Pump Inhibitors (PPIs)

Dexlansoprazole

(Kapidex, Dexilant)

CYP2C19: Poor


alleles showing

reduced activity.

Individuals with poor metabolizer status have decreased

metabolism to less active compounds; the resultant

increased concentrations may increase drug efficacy.

Individual is expected to respond well to PPI treatment; no

additional therapeutic recommendations.

Efficacy

Esomeprazole

(Nexium)

CYP2C19: Poor


alleles showing

reduced activity.






Efficacy

Lansoprazole

(Prevacid)

CYP2C19: Poor


alleles showing

reduced activity.






Efficacy

Omeprazole

(Prilosec, Zegerid)

CYP2C19: Poor


alleles showing

reduced activity.






Efficacy

Pantoprazole

(Protonix)

CYP2C19: Poor


alleles showing

reduced activity.






Efficacy

Rabeprazole

(Aciphex)

CYP2C19: Poor


alleles showing

reduced activity.






Efficacy






Page 23 of 26


Selective Serotonin Reuptake Inhibitors (SSRIs)

Citalopram

(Celexa)

CYP2C19: Poor



reduced activity.

Typical response is expected. However, individuals with

poor metabolizer status have increased bioavailability

increasing the probability of side effects.

ADR

Escitalopram

(Lexapro)

CYP2C19: Poor



reduced activity.

Typical response is expected. However, individuals with

poor metabolizer status have increased bioavailability

increasing the probability of side effects.

ADR

Fluoxetine

(Prozac)

CYP2D6: *1|*1x2 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

Paroxetine

(Paxil)

CYP2D6: Ultrarapid


showing normal

activity and one

duplicated allele

showing increased

activity.

Insufficient evidence to allow calculation of dose

adjustment. Consider selecting alternative drug (e.g.

citalopram, sertraline).

Efficacy

Sertraline

(Zoloft)

CYP2C19: Poor



reduced activity.

Individuals with poor metabolizer status may have higher

plasma concentrations and decreased clearance. Reduce

dose by 50%.

ADR

Statins

Atorvastatin

(Lipitor, Caduet)

CYP3A4: Ultra-rapid

metabolizer. Two

alleles showing

increased activity.

Individuals with ultrarapid metabolizer status eliminate

atorvastatin more rapidly than extensive/normal

metabolizers and may not respond well to a standard dose.

Increased dose may be needed.

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.






Page 24 of 26

Clinical Evidence Levels

• 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).

• 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.

• 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.

Strong

Moderate

Emerging

Reference Laboratory: Peachstate Health Management LLC d/b/a Aeon Clinical LaboratoriesLaboratory Certification: CLIA # 11D2031378Laboratory Director: Dr. Richard E. Mullins Ph.D., D.A.B.C.C.






Page 25 of 26

cboccardi

Rectangle

Patient Information Card

ISPM Labs d/b/a Capstone Diagnostics

http://www.capstonediagnostics.com

Patient: Doe, Jane

DOB: Sample ID: GeneDose Key:

1990-01-01 ex222 ACAZPCM6P

Pharmacogenomic Summary

ApoE ɛ3|ɛ3 See full GeneDose report

Factor V Leiden Variant See full GeneDose report

MTHFR (A1298C) Variant See full GeneDose report

MTHFR (C677T) Variant See full GeneDose report

Prothrombin (F2) Normal See full GeneDose report

CYP2C19 *8|*8 Poor metabolizer

CYP2C9 *1|*1 Extensive metabolizer

CYP2D6 *1|*1x2 Ultrarapid metabolizer

CYP3A4 *1B|*1B Ultrarapid metabolizer

CYP3A5*1A|*1A; or *1A|*1D; or

*1D|*1DExtensive metabolizer

CYP4F2 *1|*1 n/a

HLA-

B*1502WT|WT WT

SLCO1B1 *1|*1Normal liver uptake

activity

TPMT *1|*1 Extensive metabolizer

VKORC1 *1|*1Normal (with respect to

Warfarin)

Powered by: Coriell Life Sciences

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This card contains an abbreviated genetic summary.

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

This card shows information about your genetics that relate to

drug metabolism. Show to your doctors before being prescribed

new medications.

For additional support and guidance:

• Physicians can visit

https://alpha.genedose.com?token=prompt






Page 26 of 26


genedose genetic response report · ispm labs d/b/a capstone diagnostics 8601 dunwoody pl, ste 444...

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