Pharmacogenomics

Question 1

Pharmacogenomics, or personalized medicine, examines…

Answer 1

inherited variations in genes that determine a patient’s response to a drug (~20-40% of the differences in drug metabolism are due to genetic factors)

Question 2

abacavir (Ziagen) + abacavir-containing drugs (e.g Triumeq, Epzicom)

Answer 2

Test HLA-B*5701 be starting. (If positive, do not use)

Question 3

allopurinol (Zyloprim, Aloprim)

Answer 3

HLA-B*5801. Consider testing high-risk individuals (ex. Korean patients with kidney impairment or those with Han Chinese or Thai ancestry. If positive, do not use.

Question 4

carbamazepine (Tegretol), oxcarbazepine (Trileptal), phenytoin (Dilantin), fosphenytoin (Cerebyx)

Answer 4

HLA-B*1502. Teat all Asian patients before starting carbamazepine; testing is suggested for oxcarbazepine and is optional for phenytoin and fosphenytoin.

Question 5

clopidogrel (Plavix) is a prodrug

Answer 5

Test CYP2C19. Patients with *2 or *3 alleles and poor metabolizers and have increased CV events. If positive for these alleles, consider alternative treatments.

Question 6

codeine is a prodrug and is metabolized to morphine via…

Answer 6

CYP2D6. If a patient is a known ultra-rapid (UR) metabolizer, do not use it due to toxicity. Infant deaths have occurred when nursing mothers who were UR metabolizers took codeine.

Question 7

warfarin (Coumadin, Jantoven)

Answer 7

Increased bleeding risk due to decreased function of alleles and haplotypes (CYP2C92 and 2C93) and VKORC1 G > A variant. If these alleles are present, start with a lower dose.

Question 8

Testing is strongly recommended for:

Answer 8

• abacavir and any combo products containing abacavir
• azathioprine
• carbamazepine
• cetuximab and other EGFR inhibitors
• trastuzumab and other HER2 inhibitors

Question 9

May consider testing, though not routinely done, for:

Answer 9

• allopurinol
• capecitabine and fluorouracil
• clopidogrel
• codeine
• phenytoin and fosphenytoin
• warfarin

Question 10

trastuzumab (Herceptin) and other HER2 inhibitors

Answer 10

HER2 negative status and those with weakly positive tumors do not respond well. If tumor is HER2 negative, avoid use.

Question 11

cetuximab (Erbitux)

Answer 11

Only patients who are KRAS mutation-negative should receive these drugs. If positive for KRAS, do not use due to poor response.

Question 12

azathioprine (Azasan, Imuran)

Answer 12

If thiopurine methyltransferase (TPMT) activity is low/absent, start at a very low dose or use an alternative tx. Low/absent TPMT activity increases the risk of severe, life-threatening myelosuppression,(decreased WBCs, RBCs, and platelets).

Question 13

capecitabine (Xeloda); fluorouracil

Answer 13

Dihydropyrimidine dehydrogenase (DPD) deficiency increases the risk of severe toxicity (diarrhea, neutropenia, neurotoxicity. If DPD is deficient, do not use.