Diseases (26)
Diagnostic Testing (1)

Note:

Therapy selection and management.

Disease Management Testing (24)

Note:

Therapy selection and monitoring.


Note:

Therapy selection and monitoring.


Note:

Long term therapy selection and guidance.


Note:

Therapy selection and monitoring.


Note:

Therapy selection and management.


Note:

Therapy selection and monitoring.


Note:

Therapy selection and management.


Note:

Therapy selection and management.


Note:

Long term therapy selection.


Note:

Therapy selection and monitoring.


Note:

Long term therapy selection and monitoring.


Note:

Therapy selection and guidance.


Note:

Therapy selection and management.


Note:

Therapy selection and monitoring.


Note:

Can aid in drug selection and monitoring.


Note:

Long term therapy selection.


Note:

Therapy selection and monitoring.


Note:

Therapy selection and management.


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Hyper tension therapy selection and dosing guidance.


Note:

Therapy selection and management.


Note:

Therapy selection and monitoring.


Note:

Therapy selection and monitoring.

Other Supportive/Alternative Tests (1)

Note:

Therapy selection and monitroing.

Overview

Cytochrome P450 (CYP) represents a large superfamily of enzymes catalyzing oxidation of organic substances. CYP enzymes are integral in metabolizing both endogenous and exogenous substances, which include intermediates of lipids and steroidal hormones, drugs and toxic chemicals.

CYP3A, a subfamily of CYP450, consists of 4 genes CYP3A4, CYP3A5, CYP3A7, and CYP3A43. The substrates of the CYP3A subfamily constitute half of the drugs that are metabolized oxidatively by the CYP superfamily. Together, they help facilitate the elimination of 37% of the 200 most frequently prescribed drugs in the U.S. In adults, CYP3A4 and CYP3A5 are metabolically active and constitute approximately 30% of CYP activity. CYP3A5 expression is highly polymorphic. To date, there are 25 allelic variants of CYP3A5 (alleles numbered *1–*9).

Alleles CYP3A5 *1 and CYP3A5 *3 are distributed widely across various geographical and ethnic groups. CYP3A5 *1 represents a functional CYP3A5 while CYP3A5 *3 represents the most common non-functional variant which results in an enzyme with no activity. The CYP3A5 *3B and *6 are also null alleles resulting also in no enzyme activity. The CYP3A5 alleles *2, *8 and *9 result in an enzyme that is partially active. Individuals with CYP3A5 *1/*1 and *1/*3 genotypes express CYP3A5 and hence metabolize the substrates more rapidly than CYP3A5 *3/*3 genotype and other non-expressers. Clinically important substrates include tacrolimus (immunosuppressive drug used in organ transplantation), midazolam, saquinavir (anti-retroviral drug), vincristine (mitotic inhibitor) and the statin group of drugs. The CYP3A5 enzyme activity influences the therapeutic dosing and dose-dependent adverse reactions of these substrates.

CYP3A5 variations have been associated with certain disease states including malignancies such as acute lymphoid leukemia and chronic myeloid leukemia.

Clinical Utility
  • Determining therapeutic strategy for therapeutics that are metabolized by the CYP3A5 gene product (antidepressant and other metabolized drugs)
  • Monitor and manage tacrolimus and statin drug therapy
  • Monitor and manage pain management drug therapy
  • As an aid in therapy of prostate cancer and leukemias

Interpretation
  • If genotype CYP3A5 *1/*1* or *1/*3 or *1 other alleles are detected, this would be reported as normal to intermediate metabolizer
  • If genotype CYP3A5 *3/*3 is detected, or if CYP3A5 *1* allele is NOT detected, this would be reported as a poor metabolizer

The following is a list of major therapeutic classes with drugs that are substantially metabolized by CYP3A.

Statins: atorvastatin, simvastatin, lovastatin.

Calcium channel blockers: nifedipine, verapamil, nicardipine, felodipine, nisoldipine.

Antiplatelets: clopidogrel, prasugrel, ticagrelor, cilostazol.

Antiarrhythmics: amiodarone, quinidine, disopyramide, lidocaine.

Example of angina treatments: ranolazine.

Angiotensin II Inhibitors: losartan.

Anticoagulants: rivaroxaban, apixaban.

The following is a list of major inhibitors that compete with other drugs for a particular enzyme thus affecting the optimal level of metabolism of the substrate drug which in many cases affect the individual's response to that particular medication, e.g. making it ineffective.

Strong inhibitor is one that causes a > 5-fold increase in the plasma AUC values or more than 80% decrease in clearance. This include: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole,nefazodone, saquinavir, telithromycin

Moderate inhibitor is one that causes a > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance. This include: aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem

A Weak inhibitor is one that causes a > 1.25-fold but < 2-fold increase in the plasma AUC values or 20-50% decrease in clearance such as cimetidine, amiodarone, chloramphenicol, boceprevir, ciprofloxacin, delaviridine, diethyl, dithiocarbamate, fluvoxamine, gestodene, imatinib, mibefradil, mifepristone, norfloxacin, norfluoxetine, starfruit, telaprevir, voriconazole

Reference Ranges
CYP3A5 \*1/\*1 (Normal metabolizer)

Methodology

Allele Specific Primer Extension (ARMS) by Real-time Polymerase chain reaction (PCR), Next generation sequencing (NGS), Conventional Sequencing.

Specimen Collection

Acceptable specimens include buccal swab and peripheral blood (EDTA) or saliva. Buccal swabs can be collected by rubbing the inside of the cheeks with a swab (similar to a Q-tip and generally 4 swabs). The swabs are transported to the laboratory in a liquid medium (see manufacturer guidelines for details) or dry swab. Peripheral blood is collected through venipuncture. A minimum of 5-10 ml of whole blood is required. The specimen is collected in a lavender top (EDTA) tube.

Stability (Blood specimens):

  • Ambient: 5 days
  • Refrigerated: 7 days

Additional Testing

Therapeutic drug monitoring is the standard of care for monitoring patients on tacrolimus. Drug toxicity tests and clinical assessments are recommended for other drugs; other CYP enzymes such as CYP2D6, CYP2C19, and CYP2C9.

CPT
81231$174.81

ICD10
ICD CODE AND DESCRIPTIONLCD CODENCD CODE
C91 - Lymphoid leukemia
C91.0 - Acute lymphoblastic leukemia [ALL]
C91.9 - Lymphoid leukemia, unspecified
C95 - Leukemia of unspecified cell type
C95.0 - Acute leukemia of unspecified cell type
D68.9 - Coagulation defect, unspecified
D72.810 - Lymphocytopenia59609, 56199
D72.820 - Lymphocytosis (symptomatic)
E78 - Disorders of lipoprotein metabolism and other lipidemias
E78.0 - Pure hypercholesterolemia
E78.00 - Pure hypercholesterolemia, unspecified58812, 58801
E78.01 - Familial hypercholesterolemia58812, 58801
E78.1 - Pure hyperglyceridemia58812, 58801
E78.2 - Mixed hyperlipidemia58812, 58801
E78.4 - Other hyperlipidemia
E78.5 - Hyperlipidemia, unspecified
F06 - Other mental disorders due to known physiological condition
F06.4 - Anxiety disorder due to known physiological condition
F10.1 - Alcohol abuse
F12 - Cannabis related disorders
F12.25 - Cannabis dependence with psychotic disorder
F16 - Hallucinogen related disorders
F16.20 - Hallucinogen dependence, uncomplicated
F20 - Schizophrenia
F20.0 - Paranoid schizophrenia58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.1 - Disorganized schizophrenia58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.2 - Catatonic schizophrenia58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.3 - Undifferentiated schizophrenia58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.5 - Residual schizophrenia58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.8 - Other schizophrenia
F20.81 - Schizophreniform disorder58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.89 - Other schizophrenia58812, 58801, 58324, 58395, 57384, 58318, 57385
F20.9 - Schizophrenia, unspecified
F22 - Delusional disorders
F23 - Brief psychotic disorder
F25 - Schizoaffective disorders
F25.0 - Schizoaffective disorder, bipolar type
F25.1 - Schizoaffective disorder, depressive type
F28 - Other psychotic disorder not due to a substance or known physiological condition
F29 - Unspecified psychosis not due to a substance or known physiological condition
F30 - Manic episode
F30.10 - Manic episode without psychotic symptoms, unspecified
F31 - Bipolar disorder
F31.8 - Other bipolar disorders
F31.81 - Bipolar II disorder
F31.89 - Other bipolar disorder
F31.9 - Bipolar disorder, unspecified
F32 - Major depressive disorder, single episode
F32.0 - Major depressive disorder, single episode, mild
F32.1 - Major depressive disorder, single episode, moderate58812, 58801, 58324, 58395, 57384, 58318, 57385

Additional ICD10
ICD CODE AND DESCRIPTIONLCD CODENCD CODE
C91.0 - Acute lymphoblastic leukemia [ALL]
C91.00 - Acute lymphoblastic leukemia not having achieved remission59609, 56199, 58812, 58801
C91.01 - Acute lymphoblastic leukemia, in remission59609, 56199, 58812, 58801
C91.02 - Acute lymphoblastic leukemia, in relapse59609, 56199, 58812, 58801
C91.1 - Chronic lymphocytic leukemia of B-cell type
C91.10 - Chronic lymphocytic leukemia of B-cell type not having achieved remission59609, 56199
C91.11 - Chronic lymphocytic leukemia of B-cell type in remission59609, 56199
C91.12 - Chronic lymphocytic leukemia of B-cell type in relapse59609, 56199
C91.3 - Prolymphocytic leukemia of B-cell type
C91.30 - Prolymphocytic leukemia of B-cell type not having achieved remission59609, 56199
C91.31 - Prolymphocytic leukemia of B-cell type, in remission
C91.32 - Prolymphocytic leukemia of B-cell type, in relapse
C91.4 - Hairy cell leukemia
C91.40 - Hairy cell leukemia not having achieved remission59609, 56199
C91.41 - Hairy cell leukemia, in remission59609, 56199
C91.42 - Hairy cell leukemia, in relapse59609, 56199
C91.5 - Adult T-cell lymphoma/leukemia (HTLV-1-associated)
C91.50 - Adult T-cell lymphoma/leukemia (HTLV-1-associated) not having achieved remission59609, 56199
C91.51 - Adult T-cell lymphoma/leukemia (HTLV-1-associated), in remission
C91.52 - Adult T-cell lymphoma/leukemia (HTLV-1-associated), in relapse
C91.6 - Prolymphocytic leukemia of T-cell type
C91.60 - Prolymphocytic leukemia of T-cell type not having achieved remission59609, 56199
C91.61 - Prolymphocytic leukemia of T-cell type, in remission
C91.62 - Prolymphocytic leukemia of T-cell type, in relapse
C91.9 - Lymphoid leukemia, unspecified
C91.90 - Lymphoid leukemia, unspecified not having achieved remission
C91.91 - Lymphoid leukemia, unspecified, in remission
C91.92 - Lymphoid leukemia, unspecified, in relapse
C91.A - Mature B-cell leukemia Burkitt-type
C91.A0 - Mature B-cell leukemia Burkitt-type not having achieved remission59609, 56199
C91.A1 - Mature B-cell leukemia Burkitt-type, in remission
C91.A2 - Mature B-cell leukemia Burkitt-type, in relapse
C91.Z - Other lymphoid leukemia
C91.Z0 - Other lymphoid leukemia not having achieved remission59609, 56199
C91.Z1 - Other lymphoid leukemia, in remission
C91.Z2 - Other lymphoid leukemia, in relapse
C94.8 - Other specified leukemias
C95.0 - Acute leukemia of unspecified cell type
C95.00 - Acute leukemia of unspecified cell type not having achieved remission59609, 56199
C95.01 - Acute leukemia of unspecified cell type, in remission
C95.02 - Acute leukemia of unspecified cell type, in relapse59609, 56199
C95.1 - Chronic leukemia of unspecified cell type
C95.10 - Chronic leukemia of unspecified cell type not having achieved remission59609, 56199
C95.11 - Chronic leukemia of unspecified cell type, in remission59609, 56199
C95.12 - Chronic leukemia of unspecified cell type, in relapse59609, 56199
C95.9 - Leukemia, unspecified
C95.90 - Leukemia, unspecified not having achieved remission59609, 56199
C95.91 - Leukemia, unspecified, in remission59609, 56199
C95.92 - Leukemia, unspecified, in relapse59609, 56199
E78.0 - Pure hypercholesterolemia

References