Polypharmacy and Safer Prescribing: Why It Matters and What’s Next

As the population ages and more people live with multiple long-term conditions, the use of multiple medicines — or polypharmacy — is becoming an everyday reality in healthcare. While often necessary, polypharmacy also carries risks, including adverse drug interactions, hospital admissions, and reduced quality of life. 

In our upcoming podcast series Safe Prescribing: Navigating CYP3A and Polypharmacy, developed by EL Healthcare Education in collaboration with the Royal Pharmaceutical Society, we sat down with Professor Lauren Walker, a clinical pharmacologist and researcher, Amira Shaikh, a pharmacist and lecturer in prescribing, and several experts by experience — patients who live with the realities of managing multiple medicines daily, to explore how prescribing professionals can improve medication safety through better understanding of CYP3A-mediated drug interactions. 

Here’s a closer look at what we discussed — and why it matters. 

What Causes Polypharmacy? 

Polypharmacy arises when a person needs multiple medications to manage co-existing conditions — such as diabetes, hypertension, and depression — or to manage side effects from other drugs. This is especially common in older adults but increasingly seen in younger populations due to earlier onset of chronic conditions. 

What’s often overlooked is how these complex medication regimens can interact. For example, CYP3A4, a key enzyme in the liver and gut, is responsible for metabolising nearly half of all prescribed drugs. When multiple CYP3A-influencing drugs are prescribed, interactions can quietly occur — affecting how medicines are broken down and potentially causing harm. 

The Impact: On Patients and the Health System 

Patients described the day-to-day realities of managing multiple medicines — from balancing doses to dealing with adverse effects and navigating communication gaps between healthcare providers. These stories reflect the wider impact polypharmacy has, not just on individual health, but on healthcare systems through avoidable hospitalisations and treatment failures. 

Spotting the Risks: Tools and Clinical Judgement 

Identifying CYP3A-mediated drug interactions isn’t always straightforward. In primary care,  recognising the enzyme-level mechanism behind an interaction, in a patient with polypharmacy can be challenging. In secondary care, alert fatigue and the pressures of managing acutely unwell patients can make subtle risks easier to miss. 

Our guests shared practical tools to help, such as: 

• Liverpool Drug Interaction Checker 

• Stockley’s Interactions 

• Specialist Pharmacy Services (SPS) 

• Local ICB formulary guidance 

  
  

These tools, combined with good clinical judgment and an understanding of the patient's context (acute vs. chronic use, therapeutic window, etc.), are essential to managing interactions safely. 

Communication Is Key 

One powerful theme across all episodes was the importance of shared decision-making. Patients want clear, tailored explanations — not complex enzyme names. Explaining, for instance, that "your body breaks this medicine down more slowly, so we’re starting with a lower dose to keep you safe" builds trust and promotes adherence. 

Both Professor Lauren Walker and Amira Shaikh emphasised the importance of using simple analogies, plain language, and visual aids to support understanding, especially in vulnerable or older patients. 

Looking Ahead: Pharmacogenomics and AI 

In our conversations, we looked to the future. We explored how pharmacogenomics — using a patient’s genetic information to guide prescribing — could one day become standard practice. Genetic variations in CYP3A can explain why some patients experience side effects or why certain drugs don’t work for them. Knowing this before prescribing means clinicians can avoid trial-and-error approaches. 

We also looked at the growing role of AI. Through initiatives like the DynAIRx programme, researchers are using machine learning to identify risky prescribing patterns and streamline polypharmacy management. AI won't replace clinical judgment, but it can summarise years of medical data, spot hidden risks, and free up time for more meaningful patient conversations. 

A Final Thought 

Polypharmacy isn’t going away — but with the right knowledge, tools, and partnerships, we can make it safer.