While many drugs work very well for many people, no drug is safe and effective for everyone. Currently, physicians are largely limited to prescribing drugs according to standardized dosage guidelines, using trial and error to confirm whether an individual is receiving the right drug at the right dosage. When a medication causes harm at a standard dose, the patient is said to have suffered an adverse drug reaction (ADR).
ADRs are ranked as the fifth leading cause of death in the USA. ADRs can be mild or serious; some patients develop severe, irreversible and even lethal ADRs. In Canada, there are 200,000 severe ADRs recorded annually, accounting for the deaths of more than 10,000 Canadians and costing our health system $14-18 billion.
An individual’s susceptibility to an ADR is often determined by their genetic make-up, since genes play an important role in modulating the action and biotransformation of drugs. The normal genetic variations found in each person can result in a medication having no therapeutic benefit in some patients, or causing an ADR in others.
For example, codeine is converted by the body into morphine to deliver a painkilling effect. However, approximately 10% of people carry gene variants that reduce enzyme activity in the CYP2D6 gene. These individuals have a decreased ability to convert codeine into morphine, meaning that this drug is ineffective for them. More concerning, 1-2% of people have CYP2D6 gene duplications, which causes a faster and more powerful conversion of codeine into morphine. For these individuals – especially children – a standard, age-appropriate dose of codeine can result in toxicity, overdose and potentially death.