Comprehensive pharmacogenomic reference for CYP enzymes, metabolizer phenotypes, and gene-drug interactions to support precision prescribing.
Little to no enzyme activity. Risk of toxicity with standard doses or no effect with prodrugs.
Reduced enzyme activity. May need dose adjustments for optimal response.
Expected enzyme activity. Standard dosing typically appropriate.
Increased enzyme activity. May need higher doses or risk toxicity with prodrugs.
Cytochrome P450 2D6
Metabolizes ~25% of clinically used drugs. Highly polymorphic with >100 known allelic variants. Activity ranges from absent to ultra-rapid.
PM: 5-10% Caucasians, 1-2% Asians. UM: 1-10% depending on ethnicity (higher in Middle East, North Africa).
Critical for opioids, antidepressants, antipsychotics, tamoxifen, and beta-blockers. CPIC guidelines available.
* Prodrugs requiring CYP2D6
Clinical Pearl: CYP2D6 cannot be induced. Drug interactions occur via inhibition (fluoxetine, paroxetine, bupropion are strong inhibitors).
Cytochrome P450 2C19
Key enzyme for PPIs, antidepressants, and antiplatelets. *17 allele causes increased function (ultrarapid phenotype).
PM: 2-5% Caucasians, 12-23% Asians. *17 (UM) more common in Europeans and Africans (~20-30%).
Critical for clopidogrel activation. FDA boxed warning for CYP2C19 poor metabolizers on clopidogrel.
* Prodrug - FDA boxed warning
Clinical Pearl: For clopidogrel PMs, consider ticagrelor or prasugrel (not CYP2C19 dependent). For PPIs, PMs may have better H. pylori eradication but UMs may need higher doses.
Cytochrome P450 2C9
Metabolizes ~15% of drugs. Key variants: *2 and *3 (reduced function). Critical for warfarin and NSAIDs.
*2/*3 variants: 35% Caucasians carry ≥1 reduced function allele. Less common in African and Asian populations.
Essential for warfarin dosing algorithms. Combined with VKORC1 for personalized anticoagulation.
★ CPIC dosing algorithm
Clinical Pearl: For warfarin, use validated algorithms combining CYP2C9 + VKORC1 + clinical factors (warfarindosing.org). PMs typically require 20-50% lower doses.
Cytochrome P450 3A4 & 3A5
Most abundant CYP enzyme. Metabolizes ~50% of drugs. Highly inducible and inhibitable. CYP3A5*3 causes reduced expression.
CYP3A5 expressers: 10-30% Caucasians, 50-70% African Americans, 25-40% Asians. Significant for tacrolimus.
Drug interactions are major concern (inhibitors/inducers). CYP3A5 genotype guides tacrolimus dosing in transplant.
★ CPIC guideline for CYP3A5
Clinical Pearl: Always check for CYP3A4 inhibitors (azoles, macrolides, grapefruit) and inducers (rifampin, carbamazepine, St. John's Wort). CYP3A5 expressers need ~1.5-2x tacrolimus dose.
Cytochrome P450 1A2
Metabolizes ~15% of drugs. Highly inducible by smoking and cruciferous vegetables. *1F allele associated with inducibility.
Less genetic variation than other CYPs. Environmental factors (smoking) often more impactful than genetics.
Critical for clozapine and theophylline. Smoking cessation can dramatically increase drug levels.
★ Monitor closely with smoking changes
Clinical Pearl: Smokers metabolize clozapine/olanzapine 1.5-2x faster. Upon smoking cessation, reduce clozapine dose by 30-50% immediately to avoid toxicity. Fluvoxamine is a potent CYP1A2 inhibitor.
Cytochrome P450 2B6
Highly polymorphic enzyme. *6 allele causes reduced function. Important for HIV and psychiatric medications.
*6 allele: 25-30% African Americans, 5-10% Caucasians. Significant impact on efavirenz pharmacokinetics.
Poor metabolizers have higher efavirenz levels and more CNS side effects. CPIC guideline available for efavirenz.
★ CPIC guideline available
Clinical Pearl: CYP2B6 poor metabolizers on efavirenz may benefit from reduced dose (400mg vs 600mg) or alternative antiretroviral. Monitor for neuropsychiatric side effects.