Practicing physicians make decisions throughout the day about how to treat a patient’s medical disorders based on experience and expertise. Prescription medications are often part of a comprehensive wellness program. Doctors know that certain medications are sometimes associated with side effects, or conversely, that a patient may not get any therapeutic benefit from a drug. Variations in patient responses to medications have been known for many years. To minimize the potential for adverse reactions, physicians may elect to begin a drug therapy program using a low-dose, trial and error method. Advances in molecular genetics and biochemistry have shown genetic variants can have an effect on the production and actions of drug metabolizing enzymes.
Pharmacogenetics and Drug Response
Pharmacogenetics examines the way genetic differences affect drug response. Research has demonstrated the correlation of certain genetic variants with the way specific drugs are metabolized. These differences can affect drug responses and drug interactions. Some are well documented, such as a high potential of developing a hypersensitivity reaction to abacavir by individuals who carry variant HLA-B*57:01. Genetic testing for this gene variant is now standard before prescribing abacavir.
Another example is warfarin, a commonly prescribed anticoagulant. Warfarin is associated with adverse drug reactions such as increased risk of bleeding in people with CYP2C9 and VKORC1 variants. The FDA has issued dosage guidelines and recommends genetic testing before prescribing warfarin.
The cytochrome P450 enzymes are responsible for the metabolism of more than 70 percent of all prescription drugs. CYP2D6 is associated with the metabolism of approximately 25 percent of commonly prescribed drugs. It has more than 100 known variants that affect metabolism of many classes of drugs including psychotropic medications, beta blockers and analgesics such as pro-drugs codeine and tramadol.
People who carry variants of CYP2D6 may be at risk for adverse side effects from opioids. Poor metabolizers may not get any pain relief from codeine or tramadol. Ultra-rapid metabolizers have a higher incidence of adverse effects and toxicity with codeine because it is rapidly converted to morphine.
Clinical Applications of Pharmacogenetics for Prescribers
Genetic testing provides important information about pharmacogenetics for physicians. Pharmacogenetics can help prescribers select an appropriate drug therapy that has the potential to reduce adverse reactions, predict optimal doses and determine efficacy. Standard dosing algorithms include age, sex, medical condition, weight and use of other drugs. Including a patient’s genotype in the algorithm can help determine optimal dosing for drugs that have known genetic associations.
Pharmacogenetic testing involves collecting DNA samples from a cheek swab to determine whether a patient has genetic variants that affect drug metabolism. Samples are analyzed by MD Labs using open array technology. MD Labs is certified by Clinical Laboratory Improvement Amendments (CLIA) for pharmacogenetic testing. The Rxight test examines 60 alleles on 18 genes that are involved with the metabolism of more than 200 prescription and over-the-counter drugs.
The test includes a Personalized Medication Review® that is explained to the patient by a pharmacist trained in pharmacogenetics. Patients can keep results of testing on file with the pharmacist, who will coordinate medication and dosing recommendations with the clinician. Because a person’s genetic characteristics do not change, the test does not need to be repeated.