Cytochrome P450 3A4 and 3A5 (CYP3A4/3A5) are drug-metabolizing enzymes involved in the metabolism of several clinically important drugs, including the immunosuppressant tacrolimus. The CYP3A4 and CYP3A5 enzymes have a high degree of sequence similarity and metabolize largely the same set of drugs; genotype and metabolic activity for CYP3A4 and CYP3A5 may therefore be considered together when assessing possible effects on drug response. Individuals with some CYP3A4/3A5 alleles may experience a reduced therapeutic response to drugs that are metabolized by CYP3A4/3A5. CYP3A4/3A5 genotype information can be utilized to predict CYP3A4/3A5 metabolic phenotype, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by CYP3A4/3A5. For example, the CYP3A5*3 allele confers poor metabolic activity and has a high frequency in most populations, therefore CYP3A5*3/*3 homozygotes (poor metabolizers) predominate. Treatment with tacrolimus for a poor metabolizer typically requires standard dosing, while intermediate or rapid metabolizers typically require higher starting doses.

Variation in the CYP3A4/3A5 genes can result in normal (NM), intermediate (IM) and poor (PM) drug-metabolizing phenotypes. In general, relative to the *1 allele (normal function), the CYP3A4*22 allele has decreased function whilst CYP3A5 *3, *6 and *7 alleles have no function.

The exact effect of a particular genotype on individual drugs can vary. In addition to genotype, the metabolism of drugs may be influenced by additional factors that include enviromental, dietary and other medications; these factors and others should be considered prior to initialing a new therapy. All results must be interpreted in the context of other test results and clinical findings. Results do not rule out the possibilty of other variant alleles in CYP3A/3A5 or other vaiant alleles in other drug metabolism pathways. Patients should speak with their health care provider about the individual results of this test.

Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

Lavender (EDTA), 4mL

Immediately following collection, mix sample thoroughly by gentle inverting 8 - 10 times to prevent clotting

Lavender (EDTA), 4mL

Yellow ACD (A or B)

Immediately following collection, mix sample thoroughly by gentle inverting 8 - 10 times to prevent clotting

Yellow ACD (A or B)

Molecular Medicare billing request

Hospital clients submitting a reqeust for this assay on an outpatient with Medicare should complete and submit a Molecular Medical billing request along with the sample

• Complete and submit the form to notify us of the need for Allina Health Laboratory to bill insurance for Molecular testing performed
• All information requested is required in order for your request to be completed

Ambient (preferred) - 28 days

Refrigerated - 28 days

Frozen - 2 years

• Hemolysis
• Quantity not sufficient for analysis (QNS)
• Improper container

DNA analysis is performed by allele-specific real-time polymerase chain reactions (RT-PCR) to detect single-nucleotide polymorphisms (SNPs) and insertions within the CYP3A4/3A5 genes and to assign variant CYP3A4 *22 and CYP3A5 *3, *6, and *7 alleles. *1 denotes detection of the reference (wild-type) sequence at the assessed alleles. No other variants in this gene are detected by this assay.

Normal

Medical necessity

Hospital clients submitting a request for this assay on an outpatient with Medicare should complete and submit a Molecular Medical billing request form along with the sample.

• Complete and submit the form to notify us of the need for Allina Health Laboratory to bill insurance for Molecular testing performed
• All information requested is required in order for your request to be completed

Molecular Medicare billing request