NAPLEX - Pharmacogenomics

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Author:
daku420
ID:
307991
Filename:
NAPLEX - Pharmacogenomics
Updated:
2015-09-17 20:19:42
Tags:
genomics
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NAPLEX
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  1. HLA-B*5701
    MUST BE TESTED

    If positive ⇒ DO NOT USE abacavir ⇒ Hypersensitivity to abacavir

    • Abacavir (Ziagen)
    • Abacavir+lamivudine (Epzicom)
    • Abacavir+lamivudine+zidovudine (Trizivir)
  2. CYP2C19
    MUST BE TESTED

    If positive ⇒ consider alternative Tx

    Clopidogrel (Plavix) → prodrug

    • Must be metabolized to be efficacious
    • PMs can have higher risk of stroke due to inactivity of clopidogrel
  3. HLA-B*1502
    MUST BE TESTED

    If positive ⇒ DO NOT USE in Asians

    • Carbamazepine
    • Oxcarbazepine

    risk of Toxic Epidermal Necrolysis (TEN), Steven-Johnson Syndrome (SJS)
  4. HER2/neu
    MUST BE TESTED

    Use if positive (test must be 2+ or 3+) ⇒ for breast and gastric cancer

    • Trastuzumab (Herceptin)
    • Adotrastuzumab (Kadcyla)
    • Lapatinib (Tykerb)
    • Pertuzumab (Perjeta)
  5. K-Ras
    MUST BE TESTED

    If positive ⇒ DO NOT USE:

    • Cetuximab (Erbitux)
    • Panitumumab (Vectibix)

    ineffective in K-Ras positive
  6. EGFR
    MUST BE TESTED

    Use if positive ⇒ NSCLC

    • Cetuximab (Erbitux)
    • Erlotinib (Tarceva)
    • Afatinib (Gilotrif)
  7. CD117
    aka KIT, C-Kit

    MUST BE TESTED

    Use if positive ⇒ for Gastrointestinal stromal tumors (GIST)

    Imatinib (Gleevec)
  8. CCR-5
    MUST BE TESTED

    Use if positive ⇒ HIV

    Maraviroc (Selzentry)

    Do not use in pt with dual/mixed or CxCR-4tropic-HIV 1
  9. BCR-ABL
    MUST BE TESTED

    Use if positive ⇒ for CML

    • Imatinib (Gleevec)
    • Dasatinib (Sprycel)
    • Nilotinib (Tasigna)
    • Bosutinib (Bosulif)
    • Ponatinib (Iclusig)
  10. CD-20 (B-cell) expression
    MUST BE TESTED

    Use if positive ⇒ Non- & Hodgkin's, CLL

    • Rituximab (Rituxan)
    • Ofatumumab (Arzerra)
  11. NS3 Q80K
    MUST BE TESTED

    If positive ⇒ DO NOT USE

    Simepreviir (Olysio)
  12. Anaplastic lymphoma kinase (ALK)
    MUST BE TESTED

    Use if positive ⇒ advanced benign or metastatic NSCLC

    • Crizotinib (Xalkori)
    • Certinib (Zykadia)
  13. BRAF V600E or 
    BRAF V600K (B-RAF)
    MUST BE TESTED

    Use if positive ⇒ unresectable or metastatic melanoma

    • Vermurafenib (Zelboraf)
    • Dabrafenib (Tafinlar)
    • Trametinib (Mekinist)
  14. TPMT
    MUST BE TESTED

    If positive ⇒ DO NOT USE

    • Azathioprine
    • Mercaptopurine

    ↑'ed risk of myelosuppression in TPMT deficient pts
  15. 5q deletion
    MUST BE TESTED

    Use if positive ⇒ for Myelodysplastic syndrome

    Lenalidomide (Revlimid)
  16. MS4A1 (CD-20 antigen)
    MUST BE TESTED

    Use if positive ⇒ for Non-Hodgkin lymphoma after RELAPSE

    Tositumomab - D/c'ed due to ↓'d usage
  17. TNFRSF8 (CD-30 antigen)
    MUST BE TESTED

    Use if positive ⇒ for Hodgkin lymphoma after failure of autologous stem cell transplant; Systemic anaplastic largew cell lymphoma after previous chemo failure

    Brentuximab vedotin (Adcetris)
  18. IL2RA (CD-25) antigen
    MUST BE TESTED

    Use if positive ⇒ Cutaneous T-cell lymphoma

    Denileukin diftitox (Ontak)
  19. HLA-B*5801
    Allopurinol (Zyloprim) ⇒ for Gout

    Testing should be considered

    In Korean, Han Chinese or Thai ancestry pts

    • If positive ⇒ DO NOT USE
    • If not tested ⇒ D/c after 1st appearance of skin rash

    Can become severe: SJS
  20. CYP2D6 - Codeine
    • Use caution with ultra-rapid metabolizers
    • codeine to morphine conversion by 2D6
    • ↑'d risk for morphine tox ↝ resp. depression
    • breastmilk - fetal risk of resp. depression
  21. CYP2C9 & VKORC1 - warfarin (Coumadin, Jantoven)
    • Use caution with dose selection
    • start low if not tested
  22. Dihydropyrimidine dehydrogenase (DPD)
    If positive ⇒ DO NOT USE 

    For Breast, colon, and pancreatic cancers

    • Capecitabine (Xeloda)
    • Fluorouracil (Adrucil)

    DPD deficiency can increased drug toxicity

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