PGx 2

A key reason HLA-associated severe cutaneous adverse reactions (SCARs) are challenging to manage is that

A. They are dose-dependent and predictable B. Their incidence is uniform across all ethnicities C. HLA allele frequencies vary by ancestry, affecting population risk D. They only occur with IV formulations

A pharmacist reviewing a DTC warfarin panel for VKORC1 and CYP2C9 should be most concerned that

A. The panel includes too many rare variants B. The panel may not be performed in a CLIA-certified lab and results may differ from clinical lab genotyping C. DTC testing always underestimates bleeding risk D. VKORC1 variants have no clinical relevance

The NAVAGATE-style algorithm for deciding on PGx testing emphasizes first asking

A. Is the test reimbursed? B. Is the drug necessary and are there alternatives? C. Does the patient request the test? D. Is the test FDA-approved?

Which of the following is a key role of pharmacists in pharmacogenomic-guided medication therapy management (MTM)? A. Performing DNA sequencing in the dispensing pharmacy B. Replacing genetic counselors for all hereditary cancer testing C. Integrating PGx results with drug-drug interactions and comorbidities to optimize therapy D. Writing FDA labeling updates for PGx drugs

C. Integrating PGx results with drug-drug interactions and comorbidities to optimize therapy

Which statement about pharmacogenetic testing for a drug-metabolizing enzyme is accurate? A. Genotyping must be repeated every 5 years B. Results are generally lifelong because germline DNA sequence is stable C. The genotype changes with each drug exposure D. Test results lose validity after age 65

B. Results are generally lifelong because germline DNA sequence is stable

Which testing technology produces the most data and allows discovery of novel variants, but is more costly and analytically complex? A. Single-gene targeted PCR B. Sanger sequencing of a single exon C. Next-generation sequencing or exome sequencing D. Urine metabolite phenotyping

C. Next-generation sequencing or exome sequencing

In pre-emptive PGx panel testing results are used to

A. Guide dosing for a single index drug only B. Populate the EHR so that multiple future prescriptions can be guided by a PGx decision-support system C. Replace all clinical chemistry testing D. Eliminate the need for clinical guidelines

When interpreting a CYP2C19 diplotype, a 1/2 genotype is generally classified as

A. Normal metabolizer B. Intermediate metabolizer C. Poor metabolizer D. Ultrarapid metabolizer

A CYP2C19 2/2 genotype would be predicted to confer which phenotype? A. Normal metabolizer B. Rapid metabolizer C. Poor metabolizer D. Ultrarapid metabolizer

C. Poor metabolizer

For CYP2C19 and clopidogrel, intermediate or poor metabolizers should generally

A. Receive a higher clopidogrel dose B. Avoid clopidogrel and use an alternative such as prasugrel or ticagrelor when appropriate C. Receive aspirin only D. Be switched to warfarin

A 55-year-old man with colon cancer is being considered for capecitabine. His genotype is DPYD 1/2A (one nonfunctional allele). What is the most appropriate recommendation? A. Use capecitabine at full standard dose B. Avoid fluoropyrimidines and select an alternative regimen C. Start capecitabine at a substantially reduced dose or use a non-fluoropyrimidine regimen D. Increase capecitabine dose to overcome reduced activation

C. Start capecitabine at a substantially reduced dose or use a non-fluoropyrimidine regimen

A 68-year-old woman with atrial fibrillation brings DTC warfarin genotyping showing VKORC1-1639 AA and CYP2C9 1/1. A CLIA-certified lab repeats testing and reports VKORC1-1639 AA and CYP2C9 1/2. Which is the best pharmacist response? A. Use only the DTC result since it was obtained first B. Prefer the CLIA lab result and use a validated dosing algorithm that incorporates VKORC1 and CYP2C9 C. Ignore both results and dose empirically D. Average the two CYP2C9 genotypes

B. Prefer the CLIA lab result and use a validated dosing algorithm that incorporates VKORC1 and CYP2C9

A 45-year-old East Asian man is to start carbamazepine for trigeminal neuralgia. No prior HLA testing is available. Which approach best aligns with PGx guidance? A. Start carbamazepine immediately; HLA testing is not useful B. Order HLA-B*15

02 testing and avoid carbamazepine if positive C. Order HLA-B*57

A 60-year-old woman is starting allopurinol for gout. She is of Han Chinese ancestry. What is the most appropriate PGx-guided action? A. Initiate standard allopurinol dosing without testing B. Test for HLA-B*58

01 and avoid allopurinol if positive C. Test for HLA-B*15

A 65-year-old man is a CYP2D6 ultrarapid metabolizer and is prescribed codeine for pain. Which outcome is most concerning? A. Inadequate analgesia B. Excessive morphine levels and opioid toxicity C. Risk of serotonin syndrome D. Idiosyncratic rash

B. Excessive morphine levels and opioid toxicity

A 65-year-old man with hyperlipidemia has SLCO1B1 decreased function and is on simvastatin 40 mg daily. Which adjustment is most consistent with PGx guidance? A. Continue simvastatin 40 mg without changes B. Increase the simvastatin dose C. Switch to a lower-risk statin (e.g., pravastatin or low-dose atorvastatin) or reduce simvastatin dose with CK monitoring D. Stop all statin therapy

C. Switch to a lower-risk statin (e.g., pravastatin or low-dose atorvastatin) or reduce simvastatin dose with CK monitoring

A patient is CYP2D6 poor metabolizer and is taking fluoxetine, a strong CYP2D6 inhibitor, plus tramadol. What is the primary PGx concept illustrated? A. Gene duplication B. Phenoconversion (phenocopying of poor metabolizer status) C. Linkage disequilibrium D. Drug inhibition effect

B. Phenoconversion (phenocopying of poor metabolizer status)

A 50-year-old woman with ER-positive breast cancer and reduced-function CYP2D6 genotype is to start tamoxifen. Which option is most appropriate to discuss with the oncology team? A. Proceed with tamoxifen without considering genotype B. Consider alternative endocrine therapy (e.g., aromatase inhibitor) depending on guideline and risk-benefit C. Increase tamoxifen dose above standard D. Avoid any endocrine therapy

B. Consider alternative endocrine therapy (e.g., aromatase inhibitor) depending on guideline and risk-benefit

A 62-year-old man with NSTEMI receives a drug-eluting stent and requires dual antiplatelet therapy. His CYP2C19 genotype is 2/2. Which maintenance antiplatelet regimen is most appropriate? A. Clopidogrel plus aspirin B. Prasugrel or ticagrelor plus aspirin (if no contraindications) C. Aspirin alone D. Warfarin plus aspirin

B. Prasugrel or ticagrelor plus aspirin (if no contraindications)

A patient's SSRI choice is being guided by CYP2D6 and CYP2C19 genotypes. For a CYP2C19 poor metabolizer, which SSRI would most likely require dose reduction or alternative selection according to guidelines? A. Sertraline B. Citalopram C. Bupropion D. Mirtazapine

B. Citalopram

VKORC1-1639 G>A is most strongly associated with

A. Trastuzumab therapy selection B. Imatinib therapy for CML C. Warfarin dose requirements D. Abacavir hypersensitivity

CYP2C9 genetic variants are primarily used to guide dosing for

A. Trastuzumab B. Imatinib C. Warfarin D. Tamoxifen

BRCA1 germline variants are used to predict

A. Clopidogrel resistance B. Warfarin sensitivity C. Hereditary breast/ovarian cancer risk and PARP inhibitor eligibility D. Statin-induced myopathy

BCR-ABL fusion is the molecular target for which drug? A. Cetuximab B. Imatinib C. Tamoxifen D. 5-Fluorouracil

B. Imatinib

HER2 (ERBB2) overexpression guides the selection of therapy with

A. Simvastatin B. Trastuzumab C. Codeine D. Allopurinol