Dose Modification

Dose adjustment Chart

Best described PG cases

Medication

Potential characteristic

Enzyme/Protein

Potential therapeutic modification

Tricyclic Antidepressants

Impaired metabolism

CYP2D6 / CYP2C19

Reduce dose to 20 - 60% of standard dosages based on genotype

Warfarin and other coumadin derivatives

Impaired metabolism

CYP2C9/VKORC1

Reduce dose to 20 - 60% of standard dosages based on genotype and other physical characteristics. Multi-regression models are available to incorporate these variables.

Glipizide and other sulfonylureas

Impaired metabolism

CYP2C9

Reduce dose to 20 - 60% of standard dosages based on genotype

Phenytoin

Impaired metabolism

CYP2C9

Reduce dose to 20 - 60% of standard dosages based on genotype

Codeine

Impaired conversion to morphine

CYP2D6

Avoid in subjects with enzyme deficiency

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The information below can help you understand and apply the results of the DNA Prescription Drug Reaction Test currently offered by PGXL Laboratories.

Recent research shows that genetic variation in the drug metabolizing system is the single most important factor affecting a patient's response to drugs. The information PGXL Laboratories provides can help you determine the appropriateness and dosage of roughly a third of the most commonly prescribed drugs. To determine if medications are metabolized through these pathways, utilize the following database: Gentest's Human P450 Metabolism Database.

Testing places individuals in one of four categories:

  1. Extensive metabolizers (EM) represent the norm for metabolic capacity. Genotypes consistent with the EM phenotype include two active forms of the gene producing the drug metabolizing enzyme and therefore posses the full complement of drug metabolizing capacity. Generally, extensive metabolizers can be administered drugs which are substrates of the enzyme following standard dosing practices.
  2. Intermediate metabolizers (IM) may require lower than average drug dosages for optimal therapeutic response. In addition, multiple drug therapy should be monitored closely.
  3. 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.
  4. Ultra-extensive metabolizers (UM) may require an increased dosage due to higher than normal rates of drug metabolism. Simultaneously treating with medication that inhibits metabolization 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.

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The information presented on this site is intended as general health information and as an educational tool. It is not intended as medical advice. Only a physician, pharmacist, or other healthcare professional should advise a patient on medical issues and should do so using a medical history and other factors identified and documented as part of the health professional/patient relationship.