Sample Tamoxitest report

Interpretive Comments

Genelex offers improved detection rates using an extended Cytochrome P-450 Tag-ItTM 2D6 DNA mutation panel. This test identifies 17 small nucleotide variants and two gene rearrangements in PCR-multiplex format, providing increased sensitivity (93-97% of poor metabolite phenotypes) and quality performance. The 17 variants tested for in this assay represent the most prevalent and phenotypically relevant variations within the CYP2D6 gene.

For additional information see the CYP2D6 allele nomenclature database at http://www.cypalleles.ki.se/cyp2a6.htm 
b  For *4, no *4I designation exists
a  1661G>C, 2850C>T, and 4180G>C are found in a wide range of alleles

Testing places individuals in one of four categories:

• Normal metabolizers (NM) represent the norm for metabolic capacity. In general normal metabolizers can be administered drugs which are substrates of the CYP2D6 enzyme following standard dosing practices. Genotypes consistent with the normal metabolizer phenotype include two active CYP2D6 alleles or one active and one partially active CYP2D6 allele. Increased caution may be appropriate for individuals having one partially active allele.
  
  
• Intermediate metabolizers (IM) may require lower than average drug dose for optimal therapeutic response to medications with the exception of prodrugs. For the majority of drugs consider decreased dosage. For prodrugs, like tamoxifen, that require activation by CYP2D6, an alternative treatment or increased dose should be considered. Genotypes consistent with the intermediate metabolizer phenotype are those with one active and one inactive CYP2D6 allele, one inactive and one partially active CYP2D6 allele, or two partially active CYP2D6 alleles.
  
  
• Poor metabolizers (PM) are at increased risk of drug-induced side effects due to diminished drug elimination or for prodrugs, like tamoxifen, lack of therapeutic effect resulting from failure to generate the active form of the drug. Alternative treatment should be considered. Genotypes consistent with the poor metabolizer phenotype are those with no active CYP2D6 alleles.
  
  
• Ultra metabolizers (UM) exhibit higher than average rates of metabolism. Ultra metabolizers are at increased risk of therapeutic failure due to increased drug elimination and thus may require an increased dose of drugs that are inactivated by CYP2D6. For prodrugs, ultra metabolizers may also be at increased risk of drug-induced side effects due to increased exposure to active drug metabolites, in which case they may require lower than average doses. Genotypes consistent with ultra metabolizer phenotype include three or more active CYP2D6 alleles due to duplication of an active allele.
  
  

Co-administration of other drugs. Genotype results should be interpreted in context of the individual clinical situation. In all cases monitor for co-administration of CYP2D6 inhibitors which may convert patients to poor metabolizer status. Potential adverse outcomes included overdose toxicity or treatment failure particularly for prodrugs. For more information see GeneMedRx drug-drug and drug-gene interaction software and Cytochrome P450 Metabolism Inhibitor/Inducer Tables. Access GeneMedRx via the patient access code provided at www.GeneMedRx.com/DNAlogin.

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