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Drugs and Prescriptions Targeted by Pharmacogenomics Testing (PGx)

The benefits of pharmacogenomics testing (PGx) encompass a wide variety of prescription medications and their interactions with known genotypes.

“The effect of genetics on how some drugs are metabolized has been known for years. Genetic variants of drug metabolizing enzymes have been identified that explain differences between individuals in drug concentrations and their corresponding pharmacodynamic, including safety effects,” wrote Willard H. Dere and Tamas S. Suto in a Clinical Cases in Mineral and Bone Metabolism article more than a decade ago.

Since then, PGx testing has gained favor with a groundbreaking report released by the British Pharmacological Society and the Royal College of Physicians this year forecasting that matching drugs to DNA can kickstart a new era of medicine.

“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,” says the Mayo Clinic.

Side effects to medication can be serious, sometimes even fatal, especially for older patients.

PGx Testing: The Right Medication at the Right Dose

The Mayo Clinic’s “Pharmacogenomics - Finding the Right Medicine for You” brochure says that PGx testing can determine:

  • How likely a medication is to work for you
  • The best dose of a medication
  • If you could have serious side effects from a medication

“A pharmacogenomic test may help to predict your response to one or a few medications. However, it cannot tell you how you will respond to all medications,” the Mayo Clinic says.

Results for PGx testing are typically available in one to two weeks, though some PGx gene panels can be returned in as little as three days, and gene targeted testing can be returned in 24 to 72 hours and gene targeted point of care testing can be returned in under 24 hours and can even be completed with 30 minutes.

5 Case Studies: How PGx Helps Prescribe Proper Drugs

The “Personalized Prescribing: Using Pharmacogenomics to Improve Patient Outcomes” report from the Royal College of Physicians and British Pharmacological Society joint working party presents real-world examples of how testing a patient’s genes can prevent them from being prescribed medication that could have harmful side effects.

One breakout case study in the report regards the medicine Abacavir and the genotype HLA-B*57:01:

  • A 33-year-old man with bilateral pneumonia is found to be HIV positive and agrees to commence antiretroviral therapy (ART)
  • He undergoes genetic testing, which shows that he does not carry the HLA allele HLA-B*57:01 and is commenced on abacavir/lamivudine/dolutegravir, which he tolerates
  • Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV replication
  • The HLA allele HLA-B*57:01 was found to be strongly associated with abacavir hypersensitivity syndrome (AHS) in 2002, and a pivotal randomized controlled trial demonstrated that immunologically confirmed AHS could be eliminated by avoiding abacavir in patients with the HLA-B*57:01 allele
  • Abacavir is thus contraindicated in patients who carry the HLA-B*57:01 allele and so screening for HLA-B*57:01 prior to prescribing abacavir has been part of routine clinical care
  • Prior to introducing pre-prescription HLA-B*57:01 testing, AHS occurred in approximately 5 to 7 percent of patients receiving abacavir
  • Genetic testing for HLA-B*57:01 has been shown to be cost-effective and reduce the incidence of AHS in real-world clinical practice

“The abacavir-HLA-B*57:01 association is often considered as a paragon of pharmacogenomics in clinical practice,” says the report.

The report also includes a study on the interaction of carbamazepine, which is used to treat forms of epilepsy, bipolar affective disorder and trigeminal neuralgia, and the genotype HLA-B*15:02, which has been associated with patients developing Stevens-Johnson syndrome when prescribed Carbamazepine.

A third case study in the report regards fluoropyrimidines, antimetabolite chemotherapy drugs used in gastrointestinal, breast and head and neck cancer treatments, and DPYD genetic variants, which can increase the risk of adverse reactions with fluoropyrimidines.

A fourth case study in the report concerns codeine, an analgesic pain reliever, and the gene CYP2D6, which metabolizes codeine in the liver to activate morphine. Patients with poor metabolizers of the CYP2D6 have demonstrated that they do not receive the pain relief provided by codeine as prescribed.

A fifth case study in the report examines the interaction between clopidogrel and the drug-metabolizing enzyme CYP2C19. Clopidogrel is an antiplatelet drug indicated in patients with an acute coronary syndrome, percutaneous coronary intervention (PCI), transient ischemic attack (TIA), acute ischemic stroke and peripheral artery disease. Meta-analysis in clopidogrel-treated patients has highlighted the association between reduced-function variants in the gene CYP2C19, and increased risk of major adverse cardiovascular events, and in particular, stent thrombosis.

The Most Common Pharmacogenomic Testing Targets

The Clinical Pharmacogenetics Implementation Consortium (CPIC) lists 73 drugs where it provides genetic recommendations of known interactions.

A National Library of Medicine scholarly article in the Mental Health Clinician in 2018 lists a table of common pharmacogenomic testing targets and affected medication including:

  • CYP1A2: Clozapine
  • CYP2B6: Bupropion
  • CYP2C9: Doxepin
  • CYP2C19: Citalopram
  • CYP3A4/5: Lurasidone
  • CYP2D6: Fluoxetine
  • UGT1A4: Lamotrigine
  • UGT2B15: Lorazepam
  • COMT: Methylphenidate
  • DRD2: Haloperidol
  • ADRA2Ad: Guanfacine
  • MTHFR: Folic Acid
  • SLC6A2: Venlafaxine
  • SLC6A3: Bupropion
  • SLC6A4: Paroxetine
  • HTR2A: Quetiapine
  • HTR2C: Olanzapine
  • HLA-A*3101: Carbamazepine
  • HLA-B*1502: Carbamazepine

The article also says that there are 200 medications with pharmacogenomic information in the Food and Drug Administration labeling with some 40 neuropsychiatric medications including the following biomarker(s):

  • Amitriptyline: CYP2D6
  • Aripiprazole: CYP2D6, CYP3A4
  • Aripiprazole lauroxil: CYP2D6, CYP3A4
  • Atomoxetine: CYP2D6
  • Brexpiprazole: CYP2D6
  • Brivaracetam: CYP2C19
  • Carbamazepine: HLA-B*1502, HLA-A*3101
  • Citalopram: CYP2D6, CYP2C19
  • Clobazam: CYP2C19
  • Clomipramine: CYP2D6
  • Clozapine: CYP2D6
  • Desipramine: CYP2D6
  • Dextromethorphan/Quinidine: CYP2D6
  • Diazepam: CYP2C19
  • Doxepin: CYP2D6, CYP2C19
  • Duloxetine: CYP2D6
  • Escitalopram: CYP2D6, CYP2C19
  • Eteplirsen: DMD
  • Fluoxetine: CYP2D6
  • Fluvoxamine: CYP2D6
  • Galantamine: CYP2D6
  • Iloperidone: CYP2D6
  • Imipramine: CYP2D6
  • Lacosamide: CYP2C19
  • Modafinil: CYP2D6
  • Nefazodone: CYP2D6
  • Nortriptyline: CYP2D6
  • Oxcarbazepine: HLA-B*1502
  • Paroxetine: CYP2D6
  • Perphenazine: CYP2D6
  • Phenytoin: CYP2C9, HLA-B*1502
  • Protriptyline: CYP2D6
  • Risperidone: DYP2D6
  • Tetrabenazine: CYP2D6
  • Valproic Acid: POLG, ABL2, ASL, ASS1, NAGS, OTC
  • Venlafaxine: CYP2D6
  • Vortioxetine: CYP2D6

“Overall, pharmacogenomic testing can be beneficial to optimize treatment outcomes for patients by avoiding adverse effects and maximizing efficacy,” concluded the article.

Wise Diagnostic Systems is currently developing pharmacogenomics tests based on advanced molecular assay technologies. If we can assist you in any way, please reach out.