Scientific Foundation of Pharmacogenetics

Pharmacogenetics (PGx) is the study of genetic differences or variations in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. PGx testing can be conducted via a non-invasive buccal swab test that is simple, fast, easy, and convenient. Awareness of the genetic variations of a patient with a response to certain drugs can help physicians decide which type of drug therapy may be appropriate and most effective for individual patients and can also help the physician avoid drugs that may cause adverse reactions. Several drugs can cause severe or life-threatening reactions in patients with certain genetic variations. Some patients may experience sub-therapeutic or ineffective responses with certain drugs due to genetic variations.

In the US there are over 2 million adverse drug reactions (ADR) hospitalizations annually, with 125,000 of those resulting in death. Adverse drug reactions are considered the fourth leading cause of death in the United States. ADR’s are reported to cost as much as $136 billion dollars annually. The more drugs a patient takes, the higher the risk is of an ADR. Patients taking over 11 drugs have a 96% chance of an ADR and the average Medicare patient is on 5-8 drugs.

Many US organizations including Johns Hopkins, Mayo Clinic, Duke Medical Centre, Stanford University, Vanderbilt University Medical Centre, Cleveland Clinic. St. Jude Children’s Research Hospital and many others have adopted pharmacogenetic testing.

Why Should a Physician Order PGx Testing?

Pharmacogenetics testing can be particularly useful in:

  • Patients demonstrating sensitivity or lack of symptom relief
  • Patients with chronic conditions and multiple prescriptions
  • Patients with a history of poor compliance
  • Patients with pharmacotherapy failure

Doctors will know the following information for their patient:

  • Gene, genotype, phenotype; drug interactions for a patient’s current medications, food and alcohol
  • Free consultation with a pharmacogenetics trained pharmacist

Who Should Physicians Test?

  • Any patient who requires a higher-than-standard dosage to achieve the desired result
  • Any patient who has had a severe adverse drug reaction
  • Any patient who has had unexpected or unexplained responses to medications
  • Any patient who has had multiple unsuccessful drug trials
  • Any patient who has health issues in multiple organ systems
  • Any patient who has had multiple drug types prescribed

All of the above-mentioned criteria indicate that a patient is at an increased risk for being an abnormal metabolizer, and could be in danger from adverse events and serious side effects from prescription drug use.

Drugs, the Conditions They Treat, and PGx Warnings

The table below is a compilation of medications that have clearly stated warning labels in regards to pharmacogenetic variations. These warnings appear in different sections of the labeling. For instance, numerous medications listed below are actually “Black Box Labeled”. For other medications, the pharmacogenetic warnings are present under the contraindications section or indications and usage. The drugs usages range widely from antidepressants and schizophrenia medications to drugs used to treat pain and acid reflux.

  Drug Name Use Enzyme
Amitriptyline Bulimia, PTSD CYP2D6 poor metabolizers
Aripiprazole Schizophrenia CYP2D6 poor metabolizers
Atomoxetine ADHD CYP2D6 poor metabolizers
Carisoprodol Musculoskeletal injuries CYP2C19 poor metabolizers
Carvedilol Heart Failure, Hypertension CYP2D6 poor metabolizers
Celecoxib Pain, Inflammation CYP2C19 poor metabolizers
Cevimeline Dry mouth due to Sjorgen’s disease CYP2D6 poor metabolizers
Citalopram (1)(2) Depression CYP2C19 poor metabolizers
Clobazam Epilepsy, Anxiety CYP2C19 poor metabolizers
Clomipramine Psychiatry CYP2D6 poor metabolizers
Clopidogrel Heart disease CYP2C9 intermediate or poor metabolizers
Clozapine Schizophrenia CYP2D6 poor metabolizers
Codeine Pain CYP2D6 ultra-rapid metabolizers
Desipramine Depression CYP2D6 poor metabolizers
Dexlansoprazole (1) GERD CYP2C19 poor metabolizers
Dexlansoprazole (2) GERD CYP1A2 genotypes
Dextromethorphan and Quinidine Cough Suppressant CYP2D6 poor metabolizers
Diazepam Anxiety, Acute alcohol withdrawal, Seizures CYP2C19 poor metabolizers
Doxepin Depression, Anxiety CYP2D6 poor metabolizers
Drospirenone and Ethinyl Estradiol Preventing pregnancy CYP2C19 poor metabolizers
Esomeprazole GERD CYP2C19 poor metabolizers
Fluoxetine Depression, OCD, Bulimia CYP2D6 poor metabolizers
Flurbiprofen Pain, Inflammation CYP2C19 poor metabolizers
Fluvoxamine Depression, Social phobia, OCD CYP2D6 poor metabolizers
Galantamine Alzheimer’s disease CYP2D6 poor metabolizers
Iloperidone Schizophrenia CYP2D6 poor metabolizers
Imipramine Depression CYP2D6 poor metabolizers
Lansoprazole Acid reflux CYP2C19 poor metabolizers
Nefazodone Depression CYP2D6 poor metabolizers
Nortriptyline Depression CYP2D6 poor metabolizers
Omeprazole Acid reflux, Stomach ulcers CYP2C19 poor metabolizers
Pantoprazole GERD CYP2C19 poor metabolizers
Paroxetine Depression, OCD, Anxiety, PTSD CYP2D6 poor metabolizers
Perphenazine Schizophrenia CYP2D6 poor metabolizers
Pimozide Tourette’s syndrome CYP2D6 poor metabolizers
Prasugrel Anticoagulant CYP2C19 poor metabolizers
Propafenone Cardiac arrhythmia CYP2D6 poor metabolizers
Propranolol Tremors, Angina, Hypertension, Heart rhythm disorders CYP2D6 poor metabolizers
Protriptyline Depression CYP2D6 poor metabolizers
Quinidine Cardiac arrhythmia CYP2D6 poor metabolizers
Rabeprazole GERD CYP2C19 poor metabolizers
Risperidone Schizophrenia CYP2D6 poor metabolizers
Tetrabenazine Huntington’s chorea CYP2D6 poor metabolizers
Thioridazine Schizophrenia CYP2D6 poor metabolizers
Ticagrelor Clot prevention CYP2C19 poor metabolizers
Tolterodine Overactive bladder, Urinary incontinence CYP2D6 poor metabolizers
Tramadol Pain CYP2D6 poor metabolizers
Trimipramine Depression CYP2D6 poor metabolizers
Venlafaxine Depression CYP2D6 poor metabolizers
Voriconazole Fungal infections CYP2C9 intermediate or poor metabolizers
Vortioxetine Depression CYP2D6 poor metabolizers
Warfarin Clot prevention CYP2C9 intermediate or poor metabolizers, VKORC1

Important Note for Physicians: If patients suffer with any of the conditions listed in this table, it can be assumed that medical necessity for PGx Testing may be validated if the physician is attempting to choose the safest and most effective medication.