What is pharmacogenomics?
Pharmacogenomics is the study of how an individual’s entire genome influences their response to drugs. A pharmacogenomic test can identify variations in specific genes related to pharmacological outcomes, such as response or toxicity of certain drugs and idiosyncratic drug reactions.
Pharmacogenomic tests can be used to predict whether a drug is likely to be effective or decrease harmful effects for patients and can inform the choice and dose of a drug. Pharmacokinetics and pharmacodynamics heavily influence the efficacy and safety of drugs. Pharmacokinetics can be defined as what the body does to the drug and pharmacodynamics is what a drug does to the body. Genetic variation can alter the pharmacokinetics of a drug (eg. drug absorption, metabolism and excretion) or alter the pharmacodynamics of a drug (eg. binding of a drug to its receptor or other target).
Why primary care?
Primary care is the ideal setting for using pharmacogenomic testing as it is where 90 percent of healthcare is delivered, most prescriptions are written, where adverse drug reaction (ADR) rates are significant and where use of an electronic health record (eg. SystmOne) could potentially allow for easy storage and access to a patient’s genetic information.
In the UK, almost 60 percent of adults seen in primary care are prescribed at least one medication for which there are pharmacogenomic dosing guidelines, and approximately 20 percent of new prescriptions in primary care are for medications with pharmacogenomic dosing guidelines.
A recent study has shown that ‘pre-emptive’ pharmacogenomic testing reduced ADRs by 30 percent
However, in the UK pharmacogenomic testing is yet to be implemented in primary care. If pharmacogenomic testing were to be routinely used, it is estimated that around 20 percent of all new prescriptions in primary care might need a dose adjustment or drug switch.
Not every ADR is preventable by use of pharmacogenomic testing; however, testing may inform expected drug efficacy, enable interventions to reduce ADRs and inform monitoring plans. Indeed, a recent multi-centred, large-scale study (PREPARE) has shown that one model of ‘pre-emptive’ pharmacogenomic testing reduced ADRs by 30 percentin patient populations prescribed a drug with pharmacogenomic evidence.
Codeine: an example of pharmacogenomic testing for a commonly prescribed drug
Codeine is a commonly prescribed analgesic in primary care. It is considered a weak opioid with a potency around one-tenth that of morphine (ie. 60mg of codeine ≡ around 6mg of morphine).
Codeine is an inactive pro-drug with little or no analgesic effect until it is metabolised to morphine in the liver by the CYP2D6 enzyme.
As a result of variations in the CYP2D6 gene, individuals can be classified as slow, intermediate, normal or ultra-rapid metabolisers of drugs via this pathway. Most patients (77-97 percent) fall into the category of normal metabolisers, deriving a normal analgesic effect from morphine. However, poor metabolisers (up to 10 percent of the population) derive little or no analgesic benefit from codeine due to their inability to convert codeine to morphine. However, they may still experience ADRs.
The ultrarapid metabolisers, comprising 1-2 percent of patients, have increased CYP2D6 activity resulting in increased levels of morphine. Even low doses of codeine can potentially result in toxic levels of morphine in such patients. Knowledge of the CYP2D6 phenotype through a pharmacogenomic test could identify those patients whose response can range from inefficacy to potentially toxic effects.
What are the key benefits of pharmacogenomic testing in primary care?
- Dosing optimisation: Genetic variations can affect how quickly or slowly a patient metabolises drugs or the binding of a drug to target receptors. Pharmacogenomics can help determine the optimal dosage of a drug for an individual, thereby reducing the risk of underdosing or overdosing.
- Adverse drug reactions: Some patients may be at a higher risk of ADRs, including idiosyncratic drug reactions, due to genetic variations, eg. reaction to carbamazepine. Pharmacogenomics can identify these risks and help clinicians to avoid medications that may be problematic for patients.
- Chronic conditions management: Pharmacogenomics is especially valuable for chronic conditions managed through polypharmacy, such as diabetes, cardiovascular diseases and mental health disorders. Pharmacogenomics has the potential to be valuable in tailoring treatment plans for individual patients, thereby improving both effectiveness and patient compliance.
- Cost savings: While costs are associated with genetic testing, pharmacogenomics may ultimately lead to cost savings by reducing the trial-and-error approach to drug therapy. Patients could be less likely to experience ADRs or fail to respond to medications, which is a significant cost burden to the NHS.
- Informed decision-making: Clinicians can use pharmacogenomic information to inform their patients about the benefits and risks of medications. This shared decision-making process could improve patient satisfaction and adherence to treatment.
The opinions expressed in this article are those of the author. They do not purport to reflect the opinions or views of the UKCPA or its members. We encourage readers to follow links and references to primary research papers and guidance.
Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
