Pharmacogenomics - NAPLEX

Intermediate metabolizer (IM). This genotype yields partial enzyme activity, often requiring dose adjustments to balance efficacy and safety.

Normal (extensive) metabolizer (NM/EM). Two functional alleles provide standard enzyme activity, aligning with population norms for drug metabolism.

Poor metabolizer (PM). Two loss-of-function alleles result in negligible enzyme activity, leading to drug accumulation and increased toxicity risk.

Avoid clopidogrel; use prasugrel or ticagrelor if appropriate. Poor metabolizers have impaired clopidogrel activation, increasing cardiovascular risk, so alternatives with different metabolism are preferred.

Poor metabolizer (two loss-of-function alleles). Two loss-of-function CYP2C19 alleles diminish prodrug activation to its active metabolite, compromising antiplatelet efficacy.

Companion diagnostic / testing required in labeling. FDA requires companion diagnostics when genetic testing is necessary to ensure drug safety and efficacy prior to prescribing.

CYP2C9. CYP2C9 variants reduce warfarin metabolism, increasing sensitivity and bleeding risk, thus guiding lower initial dosing.

Use drastic dose reduction or alternative therapy. Poor metabolizer status in TPMT or NUDT15 leads to thiopurine toxicity, mandating significant dose reductions or alternative treatments.

Clinical Pharmacogenetics Implementation Consortium. CPIC develops evidence-based guidelines to translate pharmacogenetic test results into actionable prescribing recommendations.

A named haplotype (set of variants) within a gene. Star allele nomenclature designates specific combinations of genetic variants that define functional haplotypes in pharmacogenes like CYPs.

Gene affecting drug targets or pathways, altering response. Pharmacodynamic genes modulate drug-receptor interactions or signaling pathways, influencing therapeutic efficacy and potential side effects.

Gene affecting ADME, altering drug concentrations. Pharmacokinetic genes influence drug absorption, distribution, metabolism, and excretion, thereby impacting plasma levels and therapeutic outcomes.

Use of genetic variation to guide drug choice and dosing. Pharmacogenomics applies genetic information to personalize medication therapy by optimizing efficacy and minimizing adverse effects.

Avoid carbamazepine (and often oxcarbazepine) if possible. Positive HLA-B*15:02 in treatment-naïve patients elevates SJS/TEN risk, prompting selection of alternative antiepileptics.

G6PD deficiency. G6PD deficiency impairs oxidative stress handling, leading to red blood cell hemolysis upon exposure to oxidizing agents like these drugs.

Avoid allopurinol; use an alternative urate-lowering therapy. HLA-B*58:01 positivity heightens SCAR risk, requiring alternative agents like febuxostat for gout management.

HLA-B58:01. HLA-B58:01 increases susceptibility to allopurinol-induced SCAR, particularly in high-risk ancestries, necessitating pre-treatment testing.

HLA-B15:02. HLA-B15:02 is linked to increased SJS/TEN risk in susceptible populations, warranting genetic screening before carbamazepine therapy.

Do not use abacavir. Positive HLA-B*57:01 status confers high risk of life-threatening hypersensitivity, contraindicating abacavir use per guidelines.

HLA-B57:01. HLA-B57:01 variant predisposes individuals to severe immune-mediated hypersensitivity, making screening essential before abacavir initiation.

Avoid codeine due to lack of effect; use alternative analgesic. Poor CYP2D6 metabolizers fail to convert codeine to morphine, resulting in inadequate analgesia and necessitating non-opioid options.

PharmGKB (Pharmacogenomics Knowledgebase). PharmGKB curates and annotates pharmacogenomic data, providing evidence levels to inform clinical decision-making for gene-drug interactions.

Ultrarapid metabolizer (UM). Gene duplications or gain-of-function variants enhance enzyme activity, accelerating drug metabolism and potentially reducing efficacy.