Pharmacogenomics: A Guide to a New Laboratory Test to Predict Drug Responses and Improve Patient Outcomes

PATHCHAT Edition No. 63 (Version 2)
Updated: June 2022
Please contact your local Ampath pathologist for more information.

Authors:

• Dr. Jessica Trusler
• Dr. David Haarburger
• Dr. Carolyn Fedler

Introduction to Pharmacogenomics

✅ What is Pharmacogenomics?

• Pharmacogenomics studies genetic variations affecting drug response.
• It integrates genetic testing into clinical practice to optimize therapy.
• Advances in molecular technology allow simultaneous testing of multiple drug-metabolizing genes.

✅ Key Benefits of Pharmacogenomics:

• Improves drug efficacy and safety.
• Minimizes adverse drug reactions (ADRs).
• Personalizes drug selection and dosing.
• Enhances medication adherence by reducing side effects.

📌 Pharmacogenomics is transforming drug therapy by ensuring the right drug is prescribed at the right dose for each patient.

Historical Background & Early Applications

✅ Early Pharmacogenetic Discoveries:

• The concept of genetic variation in drug response was introduced in the 1940s.
• In 1959, the term pharmacogenetics was coined to describe inherited single-gene variations influencing drug metabolism.

✅ Thiopurine Methyltransferase (TPMT) Testing – A Landmark Example:

• TPMT enzyme activity influences response to thiopurine drugs (azathioprine, mercaptopurine, thioguanine).
• Key TPMT Variations:
  • 0.3% of people have no functional TPMT enzyme → Severe toxicity risk.
  • 10% have reduced TPMT activity → Higher ADR risk with standard doses.
  • 90% metabolize thiopurines normally.
• Current recommendation:
  • TPMT testing before initiating thiopurine therapy to avoid toxicity.
  • Ampath offers TPMT testing as a separate routine test.

📌 Pharmacogenomics has expanded beyond single-gene drug interactions to broader genetic panels guiding drug therapy.

Pharmacogenomics in Clinical Practice

✅ Common Drug-Gene Pairs Used in Therapy:

• CYP2C19 → Clopidogrel.
• CYP2C9/VKORC1 → Warfarin.
• CYP2D6 → Opioids, Tamoxifen.
• DPYD → Fluoropyrimidines (e.g., 5-FU, capecitabine).
• HLA-B*15:02 → Carbamazepine hypersensitivity.
• HLA-B*57:01 → Abacavir hypersensitivity.

📌 Pharmacogenomics can help reduce ADRs and improve drug response rates.

Ampath’s Pharmacogenomics Panel

✅ What Drugs Are Included?

• Ampath’s pharmacogenomics panel provides guidance on over 140 drugs across multiple clinical categories:
  • Cancer.
  • Cardiovascular disease.
  • Diabetes.
  • Gastrointestinal disorders.
  • Neurology.
  • Pain management.
  • Psychiatry.
  • Rheumatology.
  • Transplantation.
  • Urology.

✅ Why Is This Panel Important?

• Drug response varies widely among individuals (30–60% effectiveness).
• Adverse drug reactions (ADRs) contribute to:
  • 1.5 million ADR-related hospitalizations worldwide annually.
  • 6.5% of hospital admissions in the UK.
  • ADR-related deaths ranking as the 4th leading cause of in-hospital mortality in the USA.
• Annual costs of ADRs exceed $136 billion globally.
• Non-compliance due to side effects leads to one in three patients stopping medication.

📌 Pharmacogenomics helps predict drug response, reducing ADRs and hospitalizations.

Global Impact of Pharmacogenomics Testing

✅ Case Study: Pharmacogenomics Testing in the USA

• A study of 5,000 retired teachers in Kentucky taking an average of 12 medications showed:
  • 64% required immediate medication changes after testing.

✅ One Year After Medication Adjustments:

• 29% decrease in hospitalizations.
• 18% decrease in pharmacy costs.
• 24% decrease in slips and falls.

✅ Other Indirect Benefits:

• 17% reduction in healthcare plan spending after 6 months.
• 94% physician adherence to pharmacist medication review.
• 19.5% decrease in overall healthcare costs.

📌 Pharmacogenomics has a direct impact on patient outcomes and healthcare system costs.

How Pharmacogenomics Works

✅ Genetic Variations Impact Drug Metabolism:

• Enzyme mutations alter drug metabolism, leading to different responses.
• Four main classes of metabolizers have been identified:

✔ Poor Metabolizers (PMs):

• Very slow drug metabolism.
• Increased risk of drug accumulation → Toxicity.
• May require alternative drugs or lower doses.

✔ Intermediate Metabolizers (IMs):

• Reduced enzyme activity.
• Increased risk of side effects but milder than PMs.
• Dose adjustments or alternative medications may be needed.

✔ Normal Metabolizers (NMs):

• Standard drug metabolism.
• Drugs are effective and safe at standard doses.

✔ Ultra-Rapid Metabolizers (UMs):

• Very fast metabolism.
• Reduced drug effect or risk of excessive activation (in case of prodrugs like codeine).
• May require alternative therapy or higher doses.

📌 Genetic testing helps classify patients and optimize drug therapy accordingly.

Ampath’s Pharmacogenomics Test Details

✅ Genes Included in the Panel:

• Metabolism Genes:
  • COMT, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, SLCO1B1, VKORC1.
• Risk Prediction Genes:
  • Apolipoprotein E (ApoE), Factor II, Factor V Leiden, MTHFR.

✅ Sample Collection & Reporting:

• Sample: One EDTA tube (collected at any Ampath depot).
• Processing: Conducted at Ampath’s National Reference Laboratory (NRL).
• Turnaround Time: 14 days.
• Report Delivery: Secure electronic report accessible via email or Ampath’s patient portal.

📌 Patients can access a summary report or a detailed 55+ page comprehensive report online.

Key Takeaways for Clinicians

✅ Pharmacogenomics enhances drug therapy by predicting patient-specific responses.
✅ It improves medication adherence, reduces ADRs, and optimizes treatment efficacy.
✅ Ampath’s pharmacogenomics panel provides guidance for over 140 drugs across multiple medical specialties.
✅ Genetic testing helps identify poor, intermediate, normal, and ultra-rapid metabolizers, guiding dosing adjustments.
✅ Routine integration of pharmacogenomics can reduce hospitalizations and healthcare costs.

📌 For more information, contact Ampath Genetics at 012 678 1350/0645 or email geneticsclinic@ampath.co.za.