Cytochrome P450 3A5 (CYP3A5) Genotyping

Medical Test

• 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

• 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.

A 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

A 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

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

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.

3-5 days.