II. Definition
- Genetic Polymorphism as it relates to medication response
III. Examples: Cytochrome P450 genetic variants
-
CYP2D6
Gene Variants
- Poor metabolizers (5-10%)
- No response (or reduced response) to Codeine, Tramadol
- Fluoxetine and Nortriptyline risk of toxicity
- Amitriptyline, Nortriptyline, Paroxetine risk of toxicity (reduce starting dose by 50%)
- Aripiprazole (Abilify) risk of toxicity (reduce starting dose)
- Atomoxetine (Strattera) risk of toxicity (reduce starting dose)
- Ultra-metabolizers (1-2%)
- Codeine risk of toxicity (deaths have occurred)
- Amitriptyline, Nortriptyline, Paroxetine with reduced response (consider other agents)
- Poor metabolizers (5-10%)
-
CYP2C19
Gene Variants
- Poor metabolizers (2-15%)
- Clopidogrel with reduced conversion to active form (higher risk for stent closure)
- Amitriptyline and Nortriptyline risk of toxicity (reduce starting dose by 50%)
- Citalopram, Escitalopram, Sertraline risk of toxicity (reduce starting dose by 50%)
- Ultra-Metabolizers
- Citalopram, Escitalopram, Sertraline with reduced effect (consider alternative agents)
- Poor metabolizers (2-15%)
-
CYP2C9
Gene Variants
- Poor metabolizers
- Reaching a steady-state INR on Coumadin requires >3 months
- Higher risk of toxicity and bleeding complications
- Reaching a steady-state INR on Coumadin requires >3 months
- Poor metabolizers
IV. Examples: HLA Variants
- HLA-B*1502
- Carbamazepine induced Stevens–Johnson syndrome risk in asian patients (test before use)
- HLA-B*5701
- Abacavir (HIV agent) induced Hypersensitivity risk in HLA-B*5701 positive patients
V. Examples: Miscellaneous genetic variants
- TPMT Deficiency
- Severe hematologic response to Azathioprine and Mercaptopurine
- ADRB2 Variant
- Asthma status worsens on Inhaled Beta Agonist (e.g. Albuterol)
VI. Efficacy
- Pharmacogenetic testing is indicated in specific cases
- Broader screening for pharmacogenetic variation is not yet supported by the Medical Literature in 2015
- No evidence of significant benefit in Antidepressant selection