INDIVIDUAL VARIATION IN METABOLISM OF SELECT DRUGS

• Mercaptopurine

  to patients with acute lymphoblastic leukemia.
• Mercaptopurine


  Genetic variation in thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) can interfere with the metabolism of the drug, leading to an increased severity in side effects and increased risk of myelosuppression and infection.
• Irinotecan

  Genetic testing is recommended for patients with colon cancer receiving _ as part of their treatment, protocol.
• Irinotecan

  Persons with variation in the UGTIAl gene may be unable to eliminate the drug, leading to severe diarrhea and severe neutropenia, resulting in life-threatening infections.
• Abacavir

  Between 6% and 10% of patients prescribed this drug for the treatment of human immunodeficiency virus (HIV) develop potentially fatal multiorgan hypersensitivity.
• Abacavir

  Genetic testing has identified the allele HLA-B*5701 in relation to hypersensitivity. The FDA now recommends genétic testing before initiating drug therapy or restarting the drug.
• Warfarin

  This drug is a vitamin K antagonist used for prophylaxis and treatment of venous thromboembolism and for persons with atrial fibrillation or heart valve replacement, among other uses.
• Warfarin

  Alterations in CYP2C9 and vitamin K epoxide reductase (VKOR) enzymes result in decreased clearance and increased blood levels, thereby increasing the risk for bleeding. Warfarin labeling contains dosing information based on CYP2C9 and VKORC1 genotypes.
• Clopidogrel

  Persons with genetic variation in the CYP2C19 enzyme, which is necessary to convert the prodrug _, an inhibitor of platelet aggregation, to the active metabolite, may be at risk for clot for-.mation due to failure to convert the prodrug to active drug.
• Opioids

  Codeine and tramadol are prodrugs that do not exhibit analgesic properties until converted to active drug by the CYP2D6 enzyme in the liver.
• CYP2D6 enzyme

  this enzyme has several polymorphisms that alter drug metabolism.
• Opioids

  Persons with two variant alleles are considered poor metabolizers and will not achieve pain relief with this.
• Opioids

  People of Asian, Caucasian, and Middle Eastern descent are most likely to have this variant. Persons with two wild-type alleles are designated ultrarapid metabolizers and are at risk for toxicity, sedation, and respiratory depression due to higher rates of conversion of codeine or tramadol to active drug.
• Mental health drugs

  Many drugs used to treat depression (eg., tricyclic antidepressants and selective serotonin reuptake inhibitors) and other psychiatric disorders (i.e., aripiprazole for use in bipolar disorder and schizophrenia, and atomoxetine for use in ADHD) are metabolized by the CYP 2D6 enzyme.
• CYP2D6 Enzyme

  This enzyme has 90 known variants that slow drug metabolism, potentially leading to toxic drug concentrations.
• Carbamazepine

  Persons with the human leukocyte antigen (HLA) B*1502 variant should avoid using carbamazepine due to increased risk of developing Stevens-Johnson syndrome or toxic epidermal necrolysis.
• human leukocyte antigen (HLA) B*1502 variant

  Persons of Asian descent are most likely to carry this genetic variant.