BlueCross BlueShield of Tennessee Medical Policy Manual

Cytochrome p450 Genotyping


Drug efficacy and toxicity vary substantially by individual.  Because drugs and doses are typically adjusted, if needed, by trial and error, clinical consequences may include a prolonged time to optimal therapy.  Pharmacogenomics is the study of how an individual’s genetic inheritance affects the body's response to drugs. It has been investigated as a tool in predicting therapeutic failures or severe adverse drug reactions.  Pharmacogenetics tests for DNA sequence variations in drug metabolizing enzymes, drug receptors, and drug transporters. Potentially the identification of significant polymorphisms could be used to improve efficacy and safety of drug choice and /or dosage.

The cytochrome P450 (CYP450) family is a major subset of all drug-metabolizing enzymes.  Several CYP450 enzymes are involved in the metabolism of a significant proportion of currently administered drugs.  CYP2D6 metabolizes approximately 25% of all clinically used medications (e.g., dextromethorphan, beta blockers, antiarrhythmics, antidepressants and morphine derivatives).  CYP450 enzyme genes can have distinct variations which can affect individual capability to metabolize specific drugs. CYP450 genotyping has been proposed as a way to direct early selection of the most effective drug or dose to avoid significant adverse events and speed the process of achieving a therapeutic dose.

Diagnostic genotyping tests for certain CYP450 enzymes are available.  Some tests are offered as in-house laboratory-developed test services, which do not require U.S. Food and Drug Administration (FDA) approval but which must meet Clinical Laboratory Improvement Act (CLIA) quality standards for high-complexity testing.  Several testing kits for CYP450 genotyping have been cleared by FDA.  These include the AmpliChip® (Roche Molecular Systems, Inc.), the xTAG® CYP2D6 kit (Luminex Molecular Diagnostics), the INFINITI CYP2C19 Assay (AutoGenomics Inc.), Verigene CYP2C19 Nucleic Acid Test (Nanosphere Inc.), the Spartan RX CYP2C19 test system (Spartan Bioscience), and the xTAG®CYP2C19 kit v3 (Luminex Molecular Diagnostics).


See also:  Genetic Testing for Warfarin Dose




Individuals with genetic variants of cytochrome P450 have a decreased ability to metabolize clopidogrel, but the impact on clinically meaningful outcomes is uncertain.  While genotyping appears in some studies to be helpful in identifying individuals at higher risk of treatment failure and may be useful in selected individuals, more information is needed to refine optimal use of testing and to better understand the relative merit of management options.

The evidence for cytochrome P450 genotyping in individuals with various clinical conditions undergoing or being considered for treatment with a drug metabolized by CYP450 enzymes is insufficient to determine the effects of the technology on health outcomes.


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