How Your Genes Affect Your Reaction to Drugs

What patients need to know about pharmacogenomics

Doctor and patient discuss medication

Your doctor prescribes a medication. If you have a high risk of negative side effects, do you ask for something else instead? If you know the drug won’t work well for you, do you request more options?

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These questions aren’t just hypothetical. They’re at the heart of pharmacogenomics.

Pharmacogenomics is the study of how your genes affect your response to drugs. If you have certain genetic variations, some medications might be too risky for you to take. Others might offer few or no benefits. Yet others are just the right fit for you.

For perspective on this growing field, I turned to colleague and pharmacogenomics expert Kevin Hicks, PharmD, PhD. Below are a few things patients should know.

The fast metabolizer

Sometimes, patients actually process drugs too quickly.

Because of variations in a particular genes these “ultra-rapid metabolizers” transform drugs swiftly in their bodies. Unfortunately, this speedy process can lead to unexpected and exaggerated reactions.

Codeine provides the perfect example. When you take codeine, your body actually turns it into morphine to relieve pain. But if you have a certain variation of the gene CYP2D6, you may create morphine at a dangerously rapid pace.

The reaction is especially dangerous in children. Because of this, many pediatric hospitals have removed codeine as a treatment option for pain.

“Because of variations in particular genes, these ‘ultra-rapid metabolizers’ transform drugs swiftly in their bodies. Unfortunately, this speedy process can lead to unexpected and exaggerated reactions. ”

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Charis Eng, MD, PhD

Founding Chairwoman of the Genomic Medicine Institute

Side effects with few benefits

While some people metabolize drugs too quickly, others may have trouble processing them at all.

The CYP2D6 gene offers multiple examples again. In the case of codeine, some patients with a genetic variation don’t get much pain relief because their bodies don’t process the drug properly.

The same is true for antidepressants called selective serotonin reuptake inhibitors (SSRIs). If you have a certain CYP2D6 variation, you may not respond to a certain SSRI or be more likely to have a side effect.

Knowledge changes care

Knowing your genetic risk actually changes your care. That’s true for the examples above, as well as for a classic pharmacogene called G6PD, which doctors have known about since the 1950s. If you’re deficient in G6PD, you may have problems with several drugs.

G6PD deficiency typically causes no symptoms. But it does cause red blood cells, which carry oxygen, to be slightly more fragile. When exposed to certain drugs, such as some antimalarial drugs and sulfa antibiotics, red blood cells in people with G6PD deficiency break. This leads to jaundice and the inability to carry oxygen around the body.

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Because this effect is so well known, G6PD testing is usually performed before prescribing certain drugs. If you have a deficiency, doctors won’t prescribe some antimalarial drugs or sulfa antibiotics.

What does the box say?

The U.S. Food and Drug Administration (FDA) keeps a list of medications in which pharmacogenomics play a part.

However, fewer than 10 drugs rise to the level of a “boxed warning,” the FDA’s strongest warning. These include codeine (connected to CYP2D6) and the oncology drug rasburicase (connected to G6PD). Boxed warnings are more likely to trigger a test and raise awareness among doctors, pharmacists and patients.

So what’s a consumer to do? If you’re concerned about a prescription you receive, start by asking your doctors and your pharmacists questions. Does your new prescription carry a genetic risk? If so, is a test available? Are you a candidate?

Even if they don’t know the answers right away, health experts are a resource to help you find answers.

Our processes for helping doctors understand this complex, growing field aren’t perfect yet. But they’re getting better. For example, hospital systems such as the Cleveland Clinic have developed their own technology to make sure all doctors who touch your electronic health record see red flags for tests you’ve had and known medication risks. Cleveland Clinic also has an outpatient pharmacogenomics clinic.

Right now, electronic systems cover only a few medications. But with every new study — and with every new advance in genetic testing — the list grows stronger.

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Charis Eng, MD, PhD

Charis Eng, MD, PhD is founding chairwoman of the Genomic Medicine Institute and founding director of its Center for Personalized Genetic Healthcare. Dr. Eng is a global leader in cancer genetics and cancer genomic medicine.
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