mygeneRx Report mygeneRx Sample Report … · When the CYP3A4 inducer is discontinued, the dose should be reduced to the original level within 7-14 days. INFORMATIVE Sertraline Normal

mygeneRx ReportCurrent Patient MedicationsSertraline, Bupropion, Trazodone, Hypericum Perforatum, Venlafaxine, Bromazepam, Amitriptyline, Quetiapine

Amitriptyline Moderate Sensitivity to Amitriptyline (CYP2C19: Intermediate Metabolizer)

Amitriptyline should be used with caution in patients with reduced CYP2C19 activity. Consider a lower starting dose, andincrease dosing over several days until an optimal response is achieved.

ACTIONABLE

Bupropion Possibly Decreased Response to Bupropion (CYP2B6: Intermediate Metabolizer)Bupropion is metabolized to its active metabolite hydroxybupropion by CYP2B6. This metabolite contributes to thetherapeutic effects of bupropion when used as a smoking cessation agent or as an antidepressant. Individuals who areCYP2B6 intermediate metabolizers may or may not have lower blood levels of hydroxybupropion which may or may notresult in a reduced response to bupropion treatment. Bupropion can be prescribed at standard label-recommendeddosage with careful monitoring of the patient's response. Therapeutic monitoring of hydroxybupropion levels may beconsidered to guide dosing adjustment.

INFORMATIVE

Quetiapine Normal Response to QuetiapinePharmacogenetic guidance: Quetiapine is predominantly metabolized to several metabolites by CYP3A4. CYP3A5 andCYP2D6 are also responsible for quetiapine metabolism but their role in the overall metabolism of this drug is minorcompared to CYP3A4. N-desalkylquetiapine, a pharmacologically active metabolite (responsible of the antidepressanteffect) is further metabolized by CYP2D6 and CYP3A4. Preliminary studies have shown that genetic polymorphisms ofCYP3A4, CYP2D6 and CYP3A5 enzymes may be responsible in variable exposures to quetiapine and to its activemetabolite N-desalkylquetiapine. However, the clinical significance of these changes is not established yet and nogenetically guided drug selection or dosing recommendations are available. Quetiapine dose should be titrated based onthe clinical response and tolerability of the individual patient. Polypharmacy guidance: Quetiapine dose should bereduced to one sixth of original dose when co-medicated with a potent CYP3A4 inhibitor (e.g., ketoconazole,itraconazole, indinavir, ritonavir, nefazodone). When the CYP3A4 inhibitor is discontinued, the dose should be increasedby 6 fold. Quetiapine dose should be increased up to 5 fold of the original dose when used in combination with a chronictreatment (e.g. > 7-14 days) of a potent CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, St. John’s wort etc.).When the CYP3A4 inducer is discontinued, the dose should be reduced to the original level within 7-14 days.

INFORMATIVE

Sertraline Normal Sensitivity to Sertraline (CYP2C19: Intermediate Metabolizer)

Sertraline can be prescribed at standard label-recommended dosage and administration.

ACTIONABLE

Trazodone Normal Response to TrazodonePharmacogenetic guidance: Trazodone is metabolized to its active metabolite m-chlorophenylpiperazine by CYP3A4.This metabolite which may contribute to adverse events, is further metabolized by CYP2D6. The impact of geneticpolymorphisms of this enzyme on the clinical response to trazodone is not well documented. No genetically guided drugselection or dosing recommendations are available. Polypharmacy guidance: It is likely that CYP3A4 inhibitors may leadto substantial increases in trazodone plasma concentrations with the potential for adverse effects. If trazodone is usedwith a potent CYP3A4 inhibitor, the risk of cardiac arrhythmia may be increased. Therefore coadministration of trazodonewith drugs that are inhibit CYP3A4 should be approached with caution.

INFORMATIVE

Venlafaxine Normal Sensitivity to Venlafaxine (CYP2D6: Normal Metabolizer)

Venlafaxine can be prescribed at standard label-recommended dosage and administration. Careful titration isrecommended until a favorable response is achieved.

ACTIONABLE

Medications outside the scope of the report: Recognized drugs: Bromazepam Unrecognized drugs: Hypericum Perforatum

PATIENT INFORMATION SPECIMEN DETAILS

SPECIMEN TYPE:

REPORT DATE:

NAME: DOB: SEX: ACC #:

ORDERED BY:

Genetic Test Results For ---Lab Director: Thenusha Naidoo | 204 Oxford Rd, Illovo, 2095 | www.dnalysis.co.za | +27 11 268 0268 Page 1 of 15

A medication has potentially reduced efficacy, increasedtoxicity or the patient has an increased risk for theindicated condition.

Guidelines exist for adjusting dosage, increased vigilance orthe patient has a moderate risk for the indicated condition.

The medication can be prescribed according to standardregimens or the patient's risk for the indicated condition isnot increased.

ACTIONABLE

Recommendations based upon publications by international pharmacogenetic expert groups, consortia or regulatory bodies (CPIC, DPWG, FDA. EMA). Recommendations are suitable for implementation in a clinical setting. Guidelines may change as knowledge arises.

INFORMATIVE

There are insufficient or contradictory findings documenting the impact of a given genetic polymorphism or drug interaction. Recommendations are informative and implementation in a clinical setting is optional.


Risk ManagementAntipsychotic-Induced Tardive Dyskinesia

Increased Risk of Antipsychotic-Induced Tardive DyskinesiaThe patient does not carry the Taq1A variant (homozygous for the A2 allele).

Closely monitor the patient for signs of tardive dyskinesia.

The genotype results predict that the patient has normal dopamine receptor DRD2 density and hypodopaminergic functioning. The patient hasincreased risk for tardive dyskinesia when treated with antipsychotics.

Antipsychotic-Induced HyperprolactinemiaNormal Risk of Antipsychotic-Induced HyperprolactinemiaThe patient does not carry the Taq1A variant (homozygous for the A2 allele).

Monitor the patients closely for any signs of hyperprolactinemia.

The genotype results predict that the patient has normal dopamine receptor DRD2 density and hypodopaminergic functioning. The patient hasnormal risk of hyperprolactinemia when treated with antipsychotics.

Antipsychotic-Induced Weight GainLow Risk of Antipsychotic-Induced Weight GainThe patient does not carry the Taq1A variant (homozygous for the A2 allele).

Monitor the patients closely for signs weight gain.

The genotype results predict that the patient has normal dopamine receptor DRD2 density and hypodopaminergic functioning. The patient has anormal risk for weight gain when treated with antipsychotics.

Hyperlipidemia/Atherosclerotic Cardiovascular DiseaseNo increased risk of hyperlipidemia/atherosclerotic vascular diseaseThe patient is negative for the APOE 388 T>C (Arg112Cys) and 526 C>T (Cys158Arg) mutations. The patient's genotype is wild-type, which is the mostcommon genotype in the general population (frequency: >60%).

No action is needed when a patient is normolipidemic.

A patient with wild-type genotype does not have a defect in the apolipoprotein E (APOE), which is an integral structure of lipoprotein particles thathave critical roles in blood lipid metabolism and transport. Defects in APOE can increase a person's risk for developing atherosclerosis andcardiovascular disease.

Hyperhomocysteinemia - DepressionNo Increased Risk of HyperhomocysteinemiaThe patient does not carry the MTHFR C677T variant. MTHFR enzyme activity is normal.

Patients diagnosed with depression : as lower folate levels are associated with poorer antidepressant response, and baseline levels of folate within thenormal range predict antidepressant response, testing for homocysteine levels and serum folate levels is recommended for this patient beforeprescribing methylfolate as an antidepressant-augmenting agent.

Patients diagnosed with depression often have low folate levels and homocysteine is a highly sensitive marker of folate status. Functional folatedeficiency is indicated by elevated homocysteine. With a normal MTHFR activity, this patient can process folate normally and is unlikely to haveelevated plasma levels of homocysteine.

ThrombophiliaNo Increased Risk of ThrombosisThe patient does not carry the Factor V Leiden G1691A mutation or Factor II G20210A mutation (wild-type).

Unless other genetic and/or circumstantial risk factors are present (e.g., smoking or obesity…), estrogen-containing contraceptive and hormonereplacement therapy can be used by the patient.

The patient's risk of thrombosis is not increased (average risk of clotting is about 1 in 1000 for anyone in a year). However, because this test cannotfind all of the inherited reasons for abnormal clotting, other factors may affect this risk assessment.


Hyperhomocysteinemia - ThrombosisNo Increased Risk of HyperhomocysteinemiaThe patient carries two MTHFR A1298C mutations (homozygous) and no MTHFR C677T mutation. MTHFR enzyme activity is reduced (60% of normalactivity).

The patient's MTHFR activity is slightly reduced.

The patient's reduced MTHFR activity is a not a risk factor for hyperhomocysteinemia. Unless other risk factors are present, the patient is not expectedto have an increased risk for venous thromboembolism (VTE).


DRUG CLASS STANDARD PRECAUTIONS USE WITH CAUTION CONSIDER ALTERNATIVES

Anticancer Agents

Cardiovascular

Diabetes

CATEGORY

Antifolates Methotrexate

Angiotensin II Receptor Antagonists

AzilsartanCandesartanEprosartanIrbesartanLosartan

OlmesartanTelmisartanValsartan

Antianginal Agents Ranolazine

AntiarrhythmicsFlecainideMexiletine

Propafenone

Anticoagulants

ApixabanDabigatran Etexilate

EdoxabanFondaparinuxRivaroxaban

Warfarin

AntiplateletsPrasugrelTicagrelorVorapaxar

Clopidogrel

Beta Blockers

CarvedilolLabetalol

MetoprololNebivolol

PropranololTimolol

Diuretics Torsemide

Statins

AtorvastatinLovastatin

PitavastatinPravastatinSimvastatin

FluvastatinRosuvastatin

Meglitinides NateglinideRepaglinide

Sulfonylureas

ChlorpropamideGlimepiride

GlipizideGlyburide

Tolbutamide

Potentially Impacted Medications



Gastrointestinal

Infections

Pain

CATEGORY

Antiemetics

DolasetronMetoclopramide

OndansetronPalonosetron

Proton Pump Inhibitors

DexlansoprazoleEsomeprazoleLansoprazoleOmeprazolePantoprazoleRabeprazole

Antifungals Voriconazole

Antimalarials Proguanil

Fibromyalgia Agents Milnacipran

Muscle Relaxants

CarisoprodolCyclobenzaprine

MetaxaloneMethocarbamol

Tizanidine

NSAIDs

CelecoxibDiclofenac

FlurbiprofenIbuprofen

IndomethacinKetoprofenKetorolac

MeloxicamNabumetone

NaproxenPiroxicamSulindac

Opioids

AlfentanilBuprenorphine

CodeineDihydrocodeine

FentanylHydrocodone

HydromorphoneLevorphanolMeperidineMorphine

OxycodoneOxymorphone

SufentanilTapentadolTramadol

Methadone

Antiaddictives BupropionNaltrexone

Anti-ADHD Agents

AmphetamineAtomoxetine

ClonidineDextroamphetamine

GuanfacineLisdexamfetamine

DexmethylphenidateMethylphenidate



Psychotropic

CATEGORY

Anticonvulsants

BrivaracetamCarbamazepineEslicarbazepineEthosuximide

EzogabineFelbamate

FosphenytoinGabapentinLacosamideLamotrigine

LevetiracetamOxcarbazepine

PerampanelPhenytoinPregabalinRufinamideTiagabine

TopiramateValproic Acid

Vigabatrin

PhenobarbitalPrimidone

Zonisamide

Antidementia AgentsDonepezil

GalantamineMemantine

Antidepressants

AmoxapineCitalopram

DesipramineDesvenlafaxine

DuloxetineEscitalopramFluoxetine

FluvoxamineLevomilnacipran

MaprotilineMirtazapineNefazodoneNortriptylineParoxetine

ProtriptylineSertraline

VenlafaxineVilazodoneVortioxetine

AmitriptylineClomipramine

DoxepinImipramine

Trimipramine



Rheumatology

Transplantation

Urologicals

CATEGORY

Antipsychotics

AripiprazoleAsenapine

BrexpiprazoleChlorpromazine

FluphenazineHaloperidolIloperidone

LoxapineLurasidone

PaliperidonePerphenazine

PimozideQuetiapineRisperidoneThioridazineThiothixeneTrazodone

TrifluoperazineZiprasidone

ClozapineOlanzapine

Tetrabenazine

BenzodiazepinesAlprazolamClonazepamDiazepam

ClobazamLorazepamOxazepam

Mood Stabilizers Lithium

Other Neurological Agents Dextromethorphan / Quinidine

Anti-Gout Agents Allopurinol

Immunomodulators ApremilastTofacitinib Leflunomide

Immunosupressants Tacrolimus

5-Alpha ReductaseInhibitors for BenignProstatic Hyperplasia

DutasterideFinasteride

Alpha-Blockers for Benign Prostatic

Hyperplasia

AlfuzosinDoxazosinSilodosin

TamsulosinTerazosin

Antispasmodics for Overactive Bladder

DarifenacinFesoterodineMirabegronOxybutyninSolifenacinTolterodineTrospium

Phosphodiesterase Inhibitors for Erectile

Dysfunction

AvanafilSildenafilTadalafil

Vardenafil


Clopidogrel Reduced Response to Clopidogrel (CYP2C19: Intermediate Metabolizer)

Consider alternative therapy. Examples of alternative drugs: prasugrel (contraindicated in TIA/Stroke patients), ticagrelor,aspirin, aspirin plus dipyridamole.

ACTIONABLE

Allopurinol Decreased Response to Allopurinol (ABCG2: Intermediate Transporter Function)The patient carries one copy of rs2231142 A allele. Preliminary studies suggest that the patient's genotype may beassociated with a poor response to allopurinol for the treatment of gout. Carefully monitor the patient's responsivenessor consider an alternative therapy. This genotype result cannot be used to identify patients at risk for severe cutaneousadverse reactions.

INFORMATIVE

Amitriptyline Moderate Sensitivity to Amitriptyline (CYP2C19: Intermediate Metabolizer)

Amitriptyline should be used with caution in patients with reduced CYP2C19 activity. Consider a lower starting dose, andincrease dosing over several days until an optimal response is achieved.

ACTIONABLE

Bupropion Possibly Decreased Response to Bupropion (CYP2B6: Intermediate Metabolizer)Bupropion is metabolized to its active metabolite hydroxybupropion by CYP2B6. This metabolite contributes to thetherapeutic effects of bupropion when used as a smoking cessation agent or as an antidepressant. Individuals who areCYP2B6 intermediate metabolizers may or may not have lower blood levels of hydroxybupropion which may or may notresult in a reduced response to bupropion treatment. Bupropion can be prescribed at standard label-recommendeddosage with careful monitoring of the patient's response. Therapeutic monitoring of hydroxybupropion levels may beconsidered to guide dosing adjustment.

INFORMATIVE

Clobazam Possible Sensitivity to Clobazam (CYP2C19: Intermediate Metabolizer)In CYP2C19 intermediate metabolizers, plasma levels of the active metabolite N-desmethylclobazam were 2-fold higherthan those found in CYP2C19 normal metabolizers. The dose adjustment for intermediate metabolizers is not wellestablished, and therefore the recommendation for poor metabolizers is proposed. The starting dose should be 5mg/day, and dose titration should proceed slowly according to weight. Patients should be titrated initially to 10 mg /day(≤30 kg body weight) or 20 mg/day (>30 kg body weight). If necessary and based upon clinical response, an additionaltitration to the maximum doses 20 mg/day (≤30 kg body weight) or 40 mg/day (>30 kg body weight) may be started onday 21.

ACTIONABLE

Clomipramine Moderate Sensitivity to Clomipramine (CYP2C19: Intermediate Metabolizer)

Clomipramine should be used with caution in patients with reduced CYP2C19 activity. Consider a lower starting dose, andincrease dosing over several days until an optimal response is achieved.

ACTIONABLE

Clozapine Non-Response to Clozapine (CYP1A2: Normal Metabolizer - Higher Inducibility)Smokers have a high risk for non-response at standard doses and may require higher doses. There is an associationbetween high clozapine doses and the risk of seizures, and therefore careful monitoring is recommended during dosingadjustment. Smoking cessation will increase plasma drug levels, leading to adverse events. Therefore, therapeutic drugmonitoring accompanied by dose reduction is recommended in patients who have quit smoking.

INFORMATIVE

Dexmethylphenidate

Decreased Response to Dexmethylphenidate (COMT: Intermediate COMT Activity)

The patient's genotype result predicts a less optimal response to dexmethylphenidate. Dosage should be individualizedaccording to the needs and response of the patient. Therapy should be initiated in small doses, with gradual weeklyincrements.

INFORMATIVE

Dosing Guidance


Doxepin Moderate Sensitivity to Doxepin (CYP2C19: Intermediate Metabolizer)

Doxepin should be used with caution in patients with reduced CYP2C19 activity. Consider a lower starting dose, andincrease dosing over several days until an optimal response is achieved.

ACTIONABLE

Fluvastatin Increased Myotoxicty/Hepatotoxicty Risk (ABCG2: Intermediate Transporter Function)Carriers of the ABCG2 421C>A variant are at greater risk of developing adverse events to fluvastatin therapy compared tononcarriers of this mutation. Increased fluvastatin plasma concentrations due to reduced ABCG2 transport activity mayoccur in these patients. Monitor the patient for treatment-related adverse effects, and adjust dose as needed. Othermyotoxicity/hepatotoxicity predisposing factors include advanced age (≥65), diabetes, hypothyroidism, renal or hepaticimpairments, high statin dose, CYP2C9 inhibitors, ABCG2 inhibitors, and female gender.

INFORMATIVE

Imipramine Moderate Sensitivity to Imipramine (CYP2C19: Intermediate Metabolizer)

Imipramine should be used with caution in patients with reduced CYP2C19 activity. Consider a lower starting dose, andincrease dosing over several days until an optimal response is achieved.

ACTIONABLE

Leflunomide Increased Sensitivity to Leflunomide (CYP2C19: Intermediate Metabolizer)Leflunomide is metabolized by CYP2C19 and CYP1A2 to its active metabolite teriflunomide. Preliminary studies indicatethat patients with decreased CYP2C19 activity have a higher risk of developing gastrointestinal side effects andhepatotoxicity. There is insufficient data to calculate dose adjustment. If leflunomide is prescribed at standard dosing,monitor closely the patient's response and be alert to increased side effects. Full blood cell count (CBC) and liver functionparameters should be checked no more than 6 months before beginning treatment, and every month for the initial 6months of therapy. Blood pressure should be checked before beginning treatment and periodically thereafter.

INFORMATIVE

Lorazepam Possible Altered Response to Lorazepam (UGT2B15: Poor Metabolizer)

Lorazepam clearance is reduced in this patient. However, there is insufficient evidence whether this change results in asignificant clinical effect. Consider monitoring the patient for increased sedation and adjust dosing accordingly.

INFORMATIVE

Methadone Possible Sensitivity to Methadone (CYP2B6: Intermediate Metabolizer)Based on currently available evidence, S-methadone plasma concentrations may increase, resulting in higher risk ofcardiac arrhythmias and QTc prolongation. Consider lower starting doses of methadone, and adjust dosing based on theclinical response.

INFORMATIVE

Methylphenidate Decreased Response to Methylphenidate (COMT: Intermediate COMT Activity)The patient's genotype result predicts a less optimal response to methylphenidate. Dosage should be individualizedaccording to the needs and response of the patient. Therapy should be initiated in small doses, with gradual weeklyincrements.

INFORMATIVE

Naltrexone Altered Response to Naltrexone (OPRM1: Normal OPRM1 Function)Treatment of alcohol dependence: the patient has the wild-type genotype for OPRM1 that is associated with a pooreroutcome with naltrexone therapy. Naltrexone-treated patients not carrying the 118A> G mutation are less likely torespond to this drug, and may have higher relapse rates than those who are carriers of this mutation.

INFORMATIVE

Olanzapine Non-Response to Olanzapine (CYP1A2: Normal Metabolizer - Higher Inducibility)There is little evidence regarding the impact of CYP1A2 genetic variants on olanzapine response. Smokers may be at riskfor non-response at standard doses. Careful monitoring is recommended during dosing adjustment. Smoking cessationmay increase plasma drug levels, leading to adverse events. Therefore, therapeutic drug monitoring accompanied bydose reduction may be needed in patients who have quit smoking.

INFORMATIVE


Oxazepam Possible Altered Response to Oxazepam (UGT2B15: Poor Metabolizer)

Oxazepam clearance is reduced in this patient. However, there is insufficient evidence whether this change results in asignificant clinical effect. Consider monitoring the patient for increased sedation and adjust dosing accordingly.

INFORMATIVE

Phenobarbital Possible Sensitivity to Phenobarbital (CYP2C19: Intermediate Metabolizer)CYP2C19 is partly involved in the metabolism of phenobarbital, and although CYP2C19 intermediate metabolizers have alower clearance of phenobarbital than normal metabolizers, no significant changes in clinical outcome has been reportedwith this antiepileptic drug. Therefore, phenobarbital can be prescribed at standard label-recommended dosage andadministration with a closer monitoring for adverse events.

INFORMATIVE

Primidone Possible Sensitivity to Primidone (CYP2C19: Intermediate Metabolizer)CYP2C19 is partly involved in the metabolism of primidone, and although CYP2C19 intermediate metabolizers have alower clearance of phenobarbital (active metabolite) than normal metabolizers, no significant changes in clinical outcomehas been reported with this antiepileptic drug. Therefore, primidone can be prescribed at standard label-recommendeddosage and administration with a closer monitoring for adverse events.

INFORMATIVE

Rosuvastatin Increased Myopathy Risk (SLCO1B1 521T>C TT ABCG2 421C>A AC)The patient carries a polymorphism in the ABCG2 gene that is associated with a higher rosuvastatin plasma exposure. Thismay result in improved lipid-lowering response but an increased risk of adverse events. The patient does not carry apolymorphism in the SLCO1B1 gene that is associated with an increased risk of myopathy. However, because this testcannot find all of the inherited or circumstantial reasons for myopathy, other factors may affect this risk assessment.Examples of such factors include: uncontrolled hypothyroidism, renal impairment, diabetes, and comedications withABCG2 or SLCO1B1 inhibitors. For patient age 20-60 or > 60 years , the maximum recommended dose range to reducethe risk of high statin exposure: 20 mg/day. Start with usual doses 10-20 mg/day or 5 mg/day in Asian patients.

INFORMATIVE

Tetrabenazine Normal Sensitivity to Tetrabenazine (CYP2D6: Normal Metabolizer)Individualization of dose with careful weekly titration is required. The first week’s starting dose is 12.5 mg daily; secondweek, 25 mg (12.5 mg twice daily); then slowly titrate at weekly intervals by 12.5 mg to a tolerated dose. The maximumdaily dose in CYP2D6 normal metabolizers is 100 mg, with a maximum single dose of 37.5 mg . If serious adverseevents occur, titration should be stopped and the dose of tetrabenazine should be reduced. If the adverse event(s) do notresolve, consider withdrawal of tetrabenazine.

ACTIONABLE

Tizanidine Possible Non-Response to Tizanidine (CYP1A2: Normal Metabolizer - Higher Inducibility)There is little evidence regarding the impact of CYP1A2 genetic variants on tizanidine response. Smokers may be at riskfor non-response and may require higher doses. There is an association between high tizanidine plasma concentrationsand the risk of hypotension and excessive sedation. Therefore, careful monitoring is recommended during dosingadjustment. Smoking cessation may increase plasma drug levels, leading to excessive hypotension and sedation. Carefulmonitoring accompanied by dose reduction may be needed in patients who have quit smoking.

INFORMATIVE

Trimipramine Moderate Sensitivity to Trimipramine (CYP2C19: Intermediate Metabolizer)

Trimipramine should be used with caution in patients with reduced CYP2C19 activity. Consider a lower starting dose, andincrease dosing over several days until an optimal response is achieved.

ACTIONABLE

Voriconazole Moderate Sensitivity to Voriconazole (CYP2C19: Intermediate Metabolizer)

Voriconazole should be used with caution in patients with reduced CYP2C19 activity. Monitor closely voriconazole plasmaconcentrations, and adjust the dose accordingly.

ACTIONABLE


Warfarin Moderate Sensitivity to Warfarin (CYP2C9 *1/*1 VKORC1 -1639G>A A/A)Initiation Therapy: a dose decrease may be required. Consider using the following warfarin dose range provided in theFDA-approved label: 3-4 mg/day. OR consider using a personalized dose calculated by a pharmacogenetic algorithm.The estimated time to reach steady state is 4-5 days.

ACTIONABLE

Zonisamide Possible Sensitivity to Zonisamide (CYP2C19: Intermediate Metabolizer)CYP2C19 is partly involved in the metabolism of zonisamide, and although preliminary studies show that CYP2C19intermediate metabolizers have a slightly lower (15%) zonisamide clearance than normal metabolizers, no significantchange in the clinical outcome has been reported with this antiepileptic drug. Therefore, zonisamide can be prescribed atstandard label-recommended dosage and administration with a closer monitoring for adverse events.

INFORMATIVE


Test DetailsGene Genotype Phenotype Clinical ConsequencesCYP2C9 *1/*1 Normal Metabolizer Consistent with a typical CYP2C9 activity. This test did not identify risks for side

effects or loss of efficacy with drug substrates.

CYP2C19 *1/*2 Intermediate Metabolizer Consistent with a moderate deficiency in CYP2C19 activity. Potential risk for side effects or loss of efficacy with drug substrates.

CYP2D6 *1/*17 Normal Metabolizer Consistent with a typical CYP2D6 activity. This test did not identify risks for side effects or loss of efficacy with drug substrates.

CYP3A5 *3/*3 Poor Metabolizer Consistent with a poor CYP3A5 activity. This phenotype is the most common in the general population. Caution is advised when prescribing narrow therapeutic index drugs. Alternative drugs or dose adjustment may be required if CYP3A inhibitors or inducers are co-prescribed.

CYP3A4 *1/*1 Normal Metabolizer Consistent with a typical CYP3A4 activity. Caution is advised when prescribing narrow therapeutic index drugs. Alternative drugs or dose adjustment may be required if CYP3A inhibitors or inducers are co-prescribed.

VKORC1 -1639G>A A/A High Warfarin Sensitivity VKORC1 is the site of action of warfarin. The patient may require a substantial decrease in warfarin dose.

Apolipoprotein E ε3/ε3 No Increased Risk of Hyperlipidemia/Atherosclerotic Vascular Disease

No Increased Risk of Cardiovascular Disease

CYP2B6 *1/*6 Intermediate Metabolizer Consistent with a moderate deficiency in CYP2B6 activity. Potential risk for side effects or loss of efficacy with drug substrates.

CYP1A2 *1F/*1F Normal Metabolizer - Higher Inducibility

Consistent with a typical CYP1A2 activity in absence of inducing substances. Rapid Metabolism occurs in presence of inducers such as barbiturates, cruciferous vegetables, carbamazepine, rifampin and smoking.

SLCO1B1 521T>C TT Normal Transporter Function Consistent with a typical SLCO1B1 transporter function. The patient's risk for statin-induced myopathy is not increased.

COMT Val158Met AG Intermediate COMT Activity Consistent with a reduced catechol O-methyltransferase (COMT) function.

ANKK1/DRD2 DRD2:Taq1A GG Unaltered DRD2 function Consistent with a normal dopamine receptor D2 function.

OPRM1 A118G AA Normal OPRM1 Function Consistent with a normal OPRM1 receptor signaling efficiency induced by exogenous opioids. This is associated with a good analgesia following standard opioid doses and a poor response to naltrexone.

UGT2B15 *2/*2 Poor Metabolizer Consistent with a decreased UGT2B15 glucuronidation function. Potential risk for side effects with drug substrates.

ABCG2 421C>A AC Intermediate Transporter Function

Consistent with a decreased ABCG2 transporter function. The patient's risk for statin-induced adverse events is intermediate.

ADRA2A C-1291G G/G Homozygous for G Allele Carriers of the G allele of ADRA2A C-1291G variant, show greater reduction of inattentive symptoms when administered Methylphenidate or Dexmethylphenidate.

BDNF 434C>T C/T Heterozygous for rs6265 T Allele

Consistent with reduced activity-dependent secretion of BDNF from neurons and impaired BDNF signaling.

MTHFR 1298A>C CC677C>T CC

No Increased Risk of Hyperhomocysteinemia

<p>The patient's reduced MTHFR activity is a not a risk factor forhyperhomocysteinemia. Unless other risk factors are present, the patient is notexpected to have an increased risk for venous thromboembolism(VTE). </p>

Factor IIFactor V Leiden

20210G>A GG1691G>A GG

No Increased Risk of Thrombosis

<p>The patient's risk of thrombosis is not increased (average risk of clotting isabout 1 in 1000 for anyone in a year). However, because this test cannot find allof the inherited reasons for abnormal clotting, other factors may affect this riskassessment.</p>


Limitation: This test will not detect all the known alleles that result in altered or inactive tested genes. This test does not account for all individual variations in the individualtested. Absence of a detectable gene mutation does not rule out the possibility that a patient has different phenotypes due to the presence of an undetected polymorphismor due to other factors such as drug-drug interactions, comorbidities and lifestyle habits.

Methodology: Array based assays detect listed alleles, including all common and most rare variants with known clinical significance at analytical sensitivity and specificity>99%.

Disclaimer: The information presented on this report is provided as general educational health information. The Content is not intended to be a substitute for professionalmedical advice, diagnosis, or treatment. Only a physician, pharmacist or other healthcare professional should advise a patient on the use of the medicationsprescribed. DNAlysis Biotechnology developed this test and its performance characteristics. This test has not been cleared or approved by the U.S. Food and DrugAdministration. The pharmacogenetic report is one of multiple pieces of information that clinicians should consider in guiding their therapeutic choice for each patient. Itremains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to dose guidelines does not necessarily assure asuccessful medical outcome.

The pharmacogenetic assay involves non-FDA approved interpretational software and genotype-phenotype associations performed by Translational Software. A qualifieddesignee within DNAlysis Biotechnology uses Translational Software to generate and subsequently review the report.

Alleles Tested: ABCG2 421C>A; ADRA2A C-1291G; ANKK1/DRD2 DRD2:Taq1A; Apolipoprotein E ε2, ε4, (ε3 is reference); BDNF 434C>T; COMT Val158Met; CYP1A2 *1F, *1K; CYP2B6 *6, *9, *11, *18; CYP2C19 *2, *3, *4, *4B, *6, *7, *8, *9, *10, *17; CYP2C9 *2, *3, *4, *5, *6, *8, *11, *27; CYP2D6 *2, *3, *4, *4M, *6, *7,*8, *9, *10, *12, *14A, *14B, *17, *29, *35, *41; CYP3A4 *3, *12, *17, *22; CYP3A5 *3, *3C, *6, *7; Factor II 20210G>A; Factor V Leiden 1691G>A; MTHFR1298A>C, 677C>T; OPRM1 A118G; SLCO1B1 521T>C; UGT2B15 *2; VKORC1 -1639G>A


Patient Information CardThis is a summary genetic report for your patient to share with other healthcare providers. The card can be cut out along the dashed line and carried with the patient.

ABCG2 421C>A AC Intermediate Transporter Function

ADRA2A C-1291G G/G Homozygous for G AlleleANKK1/DRD2 DRD2:Taq1A GG Unaltered DRD2 function

Apolipoprotein E ε3/ε3No Increased Risk of Hyperlipidemia/Atherosclerotic Vascular Disease

BDNF 434C>T C/T Heterozygous for rs6265 T AlleleCOMT Val158Met AG Intermediate COMT Activity

CYP1A2 *1F/*1F Normal Metabolizer - Higher Inducibility

CYP2B6 *1/*6 Intermediate MetabolizerCYP2C19 *1/*2 Intermediate MetabolizerCYP2C9 *1/*1 Normal MetabolizerCYP2D6 *1/*17 Normal MetabolizerCYP3A4 *1/*1 Normal MetabolizerCYP3A5 *3/*3 Poor MetabolizerFactor II 20210G>A GG Normal Thrombosis RiskFactor V Leiden 1691G>A GG Normal Thrombosis RiskMTHFR 1298A>C CC Reduced MTHFR ActivityMTHFR 677C>T CC Normal MTHFR ActivityOPRM1 A118G AA Normal OPRM1 FunctionSLCO1B1 521T>C TT Normal Transporter FunctionUGT2B15 *2/*2 Poor MetabolizerVKORC1 -1639G>A A/A High Warfarin Sensitivity

Pharmacogenetic Test Summary

Name:

ACC #:DOB:

REPORT DETAILS

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Documents

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