pharmacogenomics

Question 1

abacavir

Answer 1

Ziagen
combo drug Triumeq, Epzicom
HLA-B*5701 positive pts are at ↑ risk for hypersensitivity reaction.

test all pt prior to start, fatal hypersensitive reaction can occur

if positive, do not use

Question 2

Allopurinol

Answer 2

Zyloprim, Aloprim
HLA-B*5801
If positive, do not use
↑ risk for SJS, D/C at the first sign of an allergic reaction
test high- risk individuals, (Korean pt w/ renal impairment or those w/ Han Chinese or Thai ancestry)

Question 3

carbamazepine
oxcarbazepine
phenytoin
fosphenytoin

Answer 3

carbamazepine (tegretol)
oxcarbazepine (trileptal)
phenytoin (dilantin)
fosphenytoin (cerebyx)

HLA-B*1502
if positive, do not use, unless benefit outweigh risk- ↑ risk for SJS and TEN
TEST all Asian pts before starting carbamazepine. optional for others

Question 4

clopidogrel

Answer 4

plavix
CYP2C19
prodrug, pt with CYP2C19*2 or *3 are poor metabolize so consider alternative tx

Question 5

Codeine

Answer 5

CYP2D6
prodrug- converted to morphine. Ultra-rapid metabolizers are at ↑ risk of opioid overdose

do not use if pt is an ultra-rapid metabolizer and if someone is a poor metabolizer do not use cause lack of efficacy

keep in mind, infant death due to nursing mother ultra-rapid metabolizer.. passed morphine to kids

Question 6

Warfarin

Answer 6

coumadin, jantoven
CYP2C9*2 and *3, VKORC1 G>A
↑ bleed risk due to reduced function, start a lower dose.

Question 7

Trastuzumab
HER2 inhibitors

Answer 7

Herceptin
Her2 gene expression required for efficacy
if the tumor is Her2 gene negative, this drug is not effective

Question 8

Cetuximab
and other EGFR inhibitors

Answer 8

Erbitux
KRAS mutation-negative are wild-type should receive this medication.
if positive for KRAS mutation, do not use

not effect in pt w/ colorectal cancer who are positive for KRAS mutation

Question 9

Azathioprine

Answer 9

Azasan, Imuran
Thiopurine methyltransferase (TPMT)
low/absent TPMT activty ↑ the risk for severe life-threatening myelosuppression. intermediate at risk too but lower

if TPMT activity is low/absent start at a very low dose or use an alternative tx

Question 10

Capecitabine
fluorouracil

Answer 10

Xeloda
DPD (dihydropyrimidine dehydrogenase) deficiency ↑ risk of severe tox (diarrhea, neutropenia, neurotoxic), do not sue if DPD deficient

Question 11

positive or negative test require action

Answer 11

POSITIVE
- HLA-B positive means ↑ hypersensitivity risk
- KRAS mutation positive predicts poor response

NEGATIVE
- HER2 negative means poor response

Question 12

genomic testing required/strongly recommended
key drugs

Answer 12

• abacavir (including combo drug w/abacavir)
• azathioprine
• carbamazepine
• cetuximab and other EGFR inhibitors
• trastuzumab and other HER2 inhibitors