Dosing Recommendations

Applying Genetic Results

Our partners at YouScript provide pharmacist-produced reports which tell you how to optimize medications now, and the YouScript analytics software can be used to quickly pick the safest and most effective medications going forward.  The information below can help you generally understand the impact of genetics determined by YouScript. YouScript, combined with DNA testing, spots individual genetic variants in the five most important drug metabolizing enzymes: CYP2D6, CYP2C9 (including VKORC1), CYP2C19, CYP3A4 and CYP3A5.

More than 85% of the population has one or more serious defects in the genes coding for these 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. To determine if medications are metabolized through these pathways, utilize the following drug list.

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.

Ultrarapid 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.