Dosing Recommendations

Drug-gene testing (also called pharmacogenomics or pharmacogenetics) characterize the study of how your genes affect your body’s response to different doses of various medications. The word “pharmacogenomics” is combined from the words pharmacology (the study of the uses and effects of medications) and genomics (the study of genes and their functions). Pharmacogenomic tests look for changes or variants in these genes that may determine whether a medication could be an effective treatment for you or whether you could have side effects to a specific medication. More than 85% of the population has one or more serious defects in the genes coding for drug-metabolizing enzymes. Recent research shows that genetic variation in the drug metabolizing system is the single most important factor affecting a patient’s response to drugs. Evidence continues to underscore how variations in human genetic makeup may help explain differences in individual responses to treatments for cancer, HIV/AIDS and depression, among other health conditions. To date, 138 drugs including codeine, proton pump inhibitors, abacavir (Ziagen, ViiV) and irinotecan now have genetic data in their FDA-approved product labeling.

PGx testing places individuals in one of four categories:

Normal Metabolizers (NM) represent the norm for metabolic capacity. Genotypes consistent with the NM phenotype include two active forms of the gene producing the drug metabolizing enzyme and therefore possess the full complement of drug metabolizing capacity. Generally, normal metabolizers can be administered drugs which are substrates of the enzyme following standard dosing practices.

Intermediate Metabolizers (IM) may require lower than average drug dosages for optimal therapeutic response for the majority of medications, prodrugs may require higher doses. In addition, multiple drug therapy should be monitored closely. Genotypes consistent with the IM phenotype are those with only one active form of the gene producing the drug metabolizing enzyme and therefore have reduced metabolic capacity.

Poor Metabolizers (PM) are at increased risk of drug-induced side effects due to diminished drug elimination or lack of therapeutic effect resulting from failure to generate the active form of the drug. Genotypes consistent with the PM phenotype are those with no active genes producing the drug metabolizing enzyme. These individuals have a deficiency in drug metabolism.

Ultra rapid Metabolizers (RM or UM) may require an increased dosage due to higher than normal rates of drug metabolism for the majority of medications, prodrugs may require lower doses. Simultaneously treating with medication that inhibits metabolism has also proven effective. Genotypes consistent with UM phenotype include three or more active genes producing the drug metabolizing enzyme and therefore have increased metabolic capacity.

Fully utilizing this type of genetic information will have profound implications for millions of patients. In 2013, U.S. pharmacies dispensed 738 million prescriptions whose uses may have been improved with PGx testing. We take genotype into account to eliminate the guesswork involved in prescribing the right medicine to the right patient at the right time. PGx information can also indicate which patients will be likely to experience adverse events with particular drugs — another application of particular interest to seniors, who often take multiple medications. PGx test results will show how each particular medication is metabolized in the liver, providing each referring physician with a laboratory analysis of many of the patient’s liver enzymes. Along with the analysis, ACLS offers a pharmacist’s report that analyzes the patient’s medication list and notes how it could be altered, based on information provided by the genomic test.

A variety of medical disciplines can benefit from studying how patients metabolize medications, including cardiovascular medicine, psychiatry and pain management. Best examples are for patients who use medications to treat heart conditions, including statins to lower cholesterol and blood thinners for the prevention of blood clots. They could benefit from PGx analysis aimed to determine dosing and avoid adverse events. People with certain genotypes have increased risk of life-threatening bleeds when introduced to the blood thinner warfarin or when dosages are changed. A dosing algorithm based on the patient’s genotype can potentially thwart this risk.

Research has shown that maintaining steady levels of opioids contributes to pain relief, but patients metabolize pain medications at different rates. Slow metabolizers of opioids may sustain dangerously high levels of opioids in the body, resulting in adverse events. Personalized knowledge of a patient’s metabolism patterns may assist in dosing. Additionally, PGx test results may assist pain physicians in demonstrating that a particular patient requires a higher medication dose to experience pain relief. For example, for an ultra-rapid metabolizer, typical doses may not control pain for high metabolizers, who run the risk of being labeled abusers.”