Pharmacogenomics

Question 1

Guidelines for PG testing

Answer 1

Clinical Pharmacogenetics Implementation Consortium (CPIC)

Question 2

Definition of allele

Answer 2

the specific form of a gene
wild-type: usually most common type of allele
homozygous gentotype: 2 identical alleles
heterozygous genotype: 2 different alleles

Question 3

Most common cause of individual variability in response to a drug

Answer 3

sing;e nucleotide polymorphism

Question 4

Which drug requires HLA-B*5701 testing in all pts before starting?

Answer 4

abacavir (Ziagen)
can lead to fatal hypersensitivity
Do not use if + test
Other drugs that contain abacavir:
Epzicom (abacavir + lamivudine)
Triumeq (abacavir + dolutegravir + lamivudine)
Trizivir (abacavir + zidovudine + lamivudine)

Question 5

Which drug requires HLA-B*5801 testing in all pts before starting?

Answer 5

Allopurinol (Zyloprim)

Can lead to increased risk of SJS

Question 6

Which drug requires HLA-B*1502 testing in all Asian pts before starting?

Answer 6

Carbamazepine (tegretol)
incr risk of SJS and toxic epidermal necrolysis (TEN)
Do not use unless benefit clearly outweighs risk
Phenytoin (Dilantin). Fosphenytoin (Cerebyx):
Testing not required, but should be considered

Question 7

What PG testing can be used for clopidogrel?

Answer 7

CYP2C19 genotype
Clopidogrel is a prodrug that is activated by 2C19
2C19*1 = fully functioning
*2/*3 = poor metabolizes
Consider alternative treatment

Question 8

What PG testing can be used for codeine?

Answer 8

CYP2D6 genotype
Codeine is metabolized to morphine via 2D6
Ultra-rapid metabolizers are at increased risk of toxicty
Poor metabolizers have lack of efficacy

Question 9

What PG testing can be used for warfarin?

Answer 9

CYP2C9 and VKORC1
2C9 2/3 = decreased metabolism
VROKC1 G > A = decreased metabolism

start with lower dose if these are present

Question 10

What PG testing can be used for Trastuzumab (Herceptin), adotrastuzumab (Kadcyla), Pertuzumab (Perjeta)?

Answer 10

HER2 gene expression

these meds only work if HER2 is expressed 2+ or 3+

Question 11

What PG testing can be used for Cetuximab (Erbitux), panitumumab (Vectibix)?

Answer 11

KRAS mutation
for colorectal cancer
If KRAS +, DO NOT USE

Question 12

What PG testing can be used for azathioprine?

Answer 12

Thiopurine methyltransferase (TPMT)
low or absent TPMT = incr risk of myelosuppression 

statrt at very low dose or use altn treatment

Question 13

What PG testing can be used for capecitabine (Xeloda), flurouracil (Adrucil)?

Answer 13

Dihydropyrimidine dehydrohenase (DPD) deficiency
can lead to incr toxicity with these drugs
do not use

Question 14

Drugs that require or strongly recommend PG testing before using:

Answer 14

Abacavir
Azathioprine
Carbamazepine 
Cetuximab, Panitumumab
HER2 inhibitors