Summary

• Pharmacogenomics (PGx) testing can help make sure your medication is safe for you to take and that it is being taken at the right dose to be effective.
• Each of us responds differently to medication depending on our genetic makeup.  
• Variations in our genes can affect how our bodies process medications.
• PGx testing looks for differences in your genes that could mean you need a different dose of your medication or need to change medications.
• It can be used before you are prescribed a medication, if your medication is not working as it should, or if is causing side effects

What is pharmacogenomics testing?

PGx is a new area of testing that can help your doctors make decisions about the medication you are being prescribed to ensure that it is safe and effective.

When your doctor prescribes medications, they choose the type and dose that usually works for most people with your condition. However, each of us responds differently to medications because of our genetic makeup.  

You inherit your genes from your parents. Genes are the instruction manuals that tell your body how to function, including how to process and use medications. You are born with your genetic makeup, and it does not change throughout your life.

We each have a unique set of genes which means our bodies process medications slightly differently. PGx testing can help your doctors understand how your body uses a medication because of your genes and find the right medication at the right dose.

Some medications can work effectively for most people but do not work well for others. If this is your situation, you may need to be prescribed a higher or lower dose or change to a different medication.

In rare cases, some medications although vital to treat serious illness, can cause harm to certain people.  

PGx testing looks for differences (called variants) in your genes in a sample of your blood or saliva to see how you will respond to the medication you are being prescribed. It will:

• show if the medication will work effectively for you,
• indicate how much of the medication you need to take for it to be effective but safe, and
• help predict if you could have a serious side effect if the medication is known to cause side effects.

A PGx test can look at one gene or several genes for specific changes that impact on the way a medication is broken down (metabolised) and used by your body. The test can be done:

• before you are prescribed a medication, 
• if a medication is not working well for you, or
• if you have any concerning side effects.

Why get tested?

PGx testing is new and around the world scientific research is adding to our knowledge about how we respond to many drugs. At present, PGx is available for a limited number of medications, but the list is expanding rapidly. Some common medications that are included in PGx testing are:

1. Allopurinol: Used to manage gout and certain types of kidney stones by reducing uric acid levels in the blood.
2. Clopidogrel: An antiplatelet medication that prevents blood clots in patients with heart disease, recent heart attack, or stroke.
3. Azathioprine: An immunosuppressant used to prevent organ transplant rejection and to treat autoimmune diseases.
4. Abacavir: An antiretroviral medication used in the treatment of HIV infection.
5. Carbamazepine: Used to treat epilepsy and bipolar disorder, it helps stabilise mood and reduce seizure frequency.

How PGx testing works

When you take a medication, your body needs to break it down and get it to the area where it is needed.

• The medication is absorbed into the bloodstream and transported to various tissues and organs.
• It is broken down mostly by the liver into small molecules called metabolites. The metabolites can be active (which means they help to treat your condition and make you better), inactive, or toxic.

Variations in your genes can affect how your body processes medications thereby influencing how effective they will be and the chance of side effects.

• To break down the drug into metabolites, your body makes enzymes. Variations in your genes affect the enzymes, resulting in faster or slower breakdown.
• Some metabolites need to attach to receptors on the surface of cells in order to work properly. Different receptors work with different metabolites. Your genes determine what type of receptors you have and how many and so affect how well metabolites can be taken up by your cells.

• Genetic variations also affect the transporter proteins that move metabolites into and out of cells. This affects how quickly a medication begins to work and how effectively it is removed from the body.

Your genes can affect how quickly your body breaks down a medication. If your body breaks it down too slowly it may mean the medication does not have time to act. You may need a higher dose or a different medication.

If the metabolites are removed too slowly from the cells in which they act, the medication can build up in your body and this can be serious. You may need a lower dose. 

Having the test

Sample

Blood.

Preparation

None.

Your results

A PGx pathology report typically includes several key sections that explain how your genetic makeup affects your response to a medication. It will include your genetic results, a clinical interpretation and prescribing recommendations. These reports are technical and you will need advice from your medical team in interpreting the results.

You may be classified as a ‘poor’, ‘intermediate’, ‘extensive’ or ‘ultrarapid’ metaboliser of each medication depending. If you are classified as being a poor or ultrarapid metaboliser you will need a different dosage of your medication, or you may be more susceptible to side effects.

An example of pharmacogenomics testing.

You will be classified according to the way you metabolise medications. As an example, Thiopurine methyltransferase therapy (TPMT) is recommended according to metaboliser status:

• Poor Metabolisers: Have very low or absent TPMT activity, leading to slower metabolism of thiopurine drugs and increased risk of toxicity.
• Intermediate Metabolisers: Have reduced TPMT activity, requiring dose adjustments.
• Normal Metabolisers: Have typical TPMT activity and usually do not need dose adjustments.

Thiopurine methyltransferase (TPMT) is an enzyme that plays a key role in the metabolism of thiopurine medications. These medications are commonly used to supress your immune system (such as to treat an autoimmune disorder like Crohn’s Disease and rheumatoid arthritis) and for chemotherapy to treat cancer. They include azathioprine, 6-mercaptopurine, and 6-thioguanine.  

The activity of the TPMT enzyme varies according to a person’s genetic makeup. If you have a low or no TPMT activity you are at a higher risk of bone marrow suppression, other severe side effects and even death – although this is rare. Testing for TPMT activity with a PGx test before starting thiopurine therapy can help your medical team adjust the dosage or choose alternative treatments to reduce the risk of severe side effects.

Online or direct-to-consumer PGx testing

PGx testing is a complex area of science, and the results of testing are often difficult to understanding. Some companies, and especially companies online, might offer you PGx testing for medications where we don’t yet fully understand how your genetic makeup affects how your body processes that medication. This means the results you receive may not be accurate or truly reflect how your body processes that medication. You may be offered this testing without needing to see a doctor – this is called “direct-to-consumer” testing.

Is it important that you have PGx testing through a reputable medical provider and have someone explain the results of the testing to you. It is also important you only having testing done for those medications where we understand how a person’s genetic makeup affects how they process it. The best way to do this is to speak with your doctor about the PGx test you want to have.

Any more to know?

Countries around the world have developed guidelines to help doctors know which medications can be tested. Here in Australia, The Royal College of Pathologists of Australasia (RCPA) has developed guidance based on the work of a committee of experts in pathology, pharmacology, and genomics. Pharmacogenomic indications in Australia.

It provides a list of medications, each with the reasons why PGx testing can be useful, and the specific gene(s) to test. It also indicates availability of testing and provides references. Please note this information is written for medical professionals and is technical. If you have any questions about the medication you are taking and whether PGx testing would be useful for you it is important to discuss this with your doctor.

PGx tests are available through some, but not all, public and private pathology providers in Australia. The number of providers, the range of tests provided, the scope of each test and the availability of a Medicare rebate are subject to change. Rather than provide a test and interpretation for a specific gene and drug, a laboratory may analyse of a panel of genes (test many genes at once) and provide prescribing guidance for multiple medications.

Finally, it is important to remember that this area of medicine is changing all the time as new thing are discovered. Genetic variations are stable throughout your life, so a PGx test needs to be done only once. As our understanding of PGx grows, other medications that are influenced by these genetic variations may be identified in the future and the interpretation of your results may need to be reassessed.

If you are taking any regular medication, you should talk to your doctor regularly to make sure the medication you are taking is effective for you. 

PGx testing and family members

You share some of your genetic makeup with your family - we all inherit half our genes from our mother and half from our father, and we pass on half of our genes to any children we have.

How you process medications is inherited from your parents, but it can also be impacted by multiple genetic and other factors, and you may not share all these factors with family members.

You do not have to share your PGx test results with your family. However, if you choose to share your result, it is important to remember that your family members will need to have to have their own PGx test if they want to find out how they will process certain medication. They should not assume they will process medications in the same way as you. If they have questions or concerns for their own health, they should speak with their doctor. 

Questions to ask your doctor

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods, medications or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

More information

Pathology and diagnostic imaging reports can be added to your My Health Record.

You and your healthcare provider can now access your results whenever and wherever needed. Get further trustworthy health information and advice from healthdirect.

Clinical Pharmogenetics Implimentation Consortium.