PGx & Polypharmacy

Reducing Risk in Complex Patients

Polypharmacy increases the likelihood of adverse drug reactions, treatment failure and unnecessary hospital admissions. While drug–drug interactions are routinely checked in clinical systems, combined gene–drug interactions and drug–drug interactions remain largely invisible without pharmacogenetic testing.

PGx helps identify how an individual is likely to respond to medicines through pathways such as SLCO1B1, ABCG2, CYP2D6, CYP2C19, CYP3A4/5 and others. This is essential in older or medically complex patients, where reduced physiological reserve amplifies the impact of inappropriate therapy, drug accumulation or reduced drug activation.

Evidence suggests that 20–30% of potentially serious adverse drug events are linked to drug metabolism differences — many of which PGx can reveal before harm occurs. When combined with a prescribing platform capable of identifying both pharmacodynamic and pharmacokinetic interactions, PGx becomes a powerful tool for safer, more effective polypharmacy management.
 
Key Takeaways

• Polypharmacy patients are at heightened risk of hidden drug–drug and gene–drug interactions?
• PGx identifies metaboliser status for key CYP P450 pathways such as CYP2D6 and CYP2C19?
• Supports selection of medications with lower adverse interaction potential?
• Helps avoid toxicity, underdosing, or cumulative side effects?
• Improves clinical confidence in complex prescribing decisions

Clinical Example: Hidden Risk in an Elderly Polypharmacy Patient

A 78-year-old patient is prescribed amitriptyline for neuropathic pain, alongside metoprolol, tramadol and omeprazole. Despite adherence, the patient experiences fatigue, dizziness and inadequate pain relief.

PGx testing identifies the patient as a CYP2D6 poor metaboliser, significantly reducing the metabolism of amitriptyline and metoprolol, increasing plasma concentrations of both. The patient is also a CYP2C19 poor metaboliser, affecting omeprazole clearance and altering stomach pH — which in turn changes the absorption of several other medicines.

• When the prescribing platform evaluates the entire regimen, it flags:
• Elevated amitriptyline levels → risk of anticholinergic toxicity
• Reduced tramadol activation → inadequate analgesia
• Elevated metoprolol levels → bradycardia and fatigue risk
• Multiple metabolism bottlenecks due to overlapping CYP inhibition

A revised regimen using alternatives with reduced CYP2D6/CYP2C19 dependency leads to improved symptom control, reduced side effects and a more stable overall treatment response.

Frequently Asked Questions

Why is PGx especially important in older patients?

Reduced renal and hepatic function magnify the impact of metaboliser status, increasing the risk of drug accumulation.

Can PGx detect drug–drug interactions?

Indirectly — PGx shows how a patient metabolises drugs. When combined with a prescribing platform, gene–drug and drug–drug interactions become visible.

Which pathways matter most in polypharmacy?

CYP2D6, CYP2C19, CYP3A4/5, SLCO1B1 and UGT pathways contribute significantly to risk.

Does this replace standard interaction checkers?

No — it adds genetic context, improving the accuracy of existing interaction tools.

How quickly can PGx influence a prescribing decision?

Reports are typically available within 14 days and can guide both acute adjustments and long-term medication optimisation.