Pharmacogenomics : Drug Intolerances and Genes
When you look in the dictionary under ”drug intolerances and genes” you will find my name.
I have written widely about the effects that adverse drug reactions have had on my health. Simplistically, I have drug allergies and I am a poor metabolizer of CYP2D6 which means medicines that utilize this gene are toxic for me.
But a new world of pharmacogenomics has changed all of that making essential medicines available to me.
Pharmacogenomics is the branch of medicine that predicts an individual’s response to medicines before they take them.
It takes the guesswork out of the right medicine in the right dose for the individual.
Whilst there are many factors to safe medicines, pharmacogenomics is often overlooked, and yet has a profound impact on medicine safety.
So this is why it matters.
One Size Does Not Fit All
Current Australian prescribing guidelines adopt a “one size fits all” model.
Yet, medical scientists, drug companies, and regulators have known for decades, that any given medicine, is only effective in 60 to 70% of people. Antidepressants and statins have significantly worse outcomes than this.
Dr. Allen Roses, of Glaxo Smith Kline, has even stated that:
“The vast majority of drugs – more than 90 percent – only work in 30 or 50 percent of the people,”
“I wouldn’t say that most drugs don’t work. I would say that most drugs work in 30 to 50 percent of people. Drugs out there on the market work, but they don’t work in everybody.”
Simplistically, despite a system that works on “averages,” there are not a lot of averages, such that the quality use of medicines needs the individual to be considered.
Current Australian prescribing practices do not consider the individual. One of the main ways to consider the individual is through pharmacogenomic testing.
When Medicine Acts Promiscuously
This law of average approach also has a number of other problems.
When a medicine does not act as intended it is common practice to simply increase the dosage or to add additional medicine. That is to guess.
This can be a risky strategy where:
- The dosage was too high not to low for the individual.
- The individual cannot use the medicine and an alternative medicine would work.
- Additional medicines interact (called poly-pharmacy). With every additional medicine the risk of this increases.
- It is difficult to simply stop the medicine.
All medicines have risks. Some medicines are very effective for some people. Some provide little benefit. In other cases, they may even cause severe harm.
For example, in June 2018, the Therapeutic Goods Administration issued a warning, that a significant number of medications cause severe adverse reactions including suicide, including a broad range of anti-depressants, attention deficit hyperactivity disorder medications, seasonal allergy medicines, smoking cessation medicines, and acne medicines. Could this be due to pharmacogenomics?
This is especially so in people whose genes affect the availability and detoxification of medicines.
Importantly, one study showed that patients who metabolize very slowly or too fast have 4 times more disability claims than those with normal pharmacogenomic test results.
This means that in some people the risk is not merely inconvenient but permanently disabling.
It seems to me to be barbaric to prefer to guess particularly for high-risk medicines including ones that cannot simply be withdrawn.
What if the right medicine and the right dosage was determined from the outset? What if the wrong medicine in the wrong dosage led to a permanent disability?
Pharmacogenomics: Considering the Individual
The quality use of medicine demands that the individual is taken into account. Pharmacogenomics considers the individual.
An individual’s genes (and particularly four key genes – CYP2D6, CYP2C19, CYP2C9, and CYP3A4) determine how an individual will respond to medicines.
These four genes process approximately 80% of all medicines.
They are highly variable between people including specific ethnic groups. Therefore drug response varies significantly.
Depending on the activity of these genes the medicine works, does not work, or causes severe adverse drug reactions if not long-term disability due to toxicity.
Around 10% of Caucasians are at severe risk of hospitalization, death, and disability if given the “average” dose of certain medicines. 40% need a higher or lower dose to get the desired effects.
In other ethnic groups including Asian, Pacific Islanders, and Africans, the risk is significantly higher. Approximately 70% (rather than 10%) are at risk if given the “average” dose. The pharmacogenomic makeup of descendants of aboriginal persons is currently subject to a detailed study.
The point is this is an inherited condition.
If your paternal or maternal family have a history of adverse medicine reactions then please consider getting tested.
But why stop there.
The test has a lifelong application, so what if all children were tested at birth so that throughout their life, they got the right medicine in the right dose? It seems a small price to pay.
Pharmacogenomic Testing
There are now several pathology companies providing genetic testing for how people react to drugs. Within Australia testing can be done via www.mydna.life. Within the USA it can be done via www.genesight.com. 23andMe does not test the complete sequence.
Once tested there are now official recommendations on medicine choice and dosages for any given test result.
The first one was developed by the Pharmacogenetic Working Group of the Royal Dutch Association for the Advancement of Pharmacy (DPWG) and this has been incorporated into the National Dutch electronic prescribing system and so are available to every pharmacist and doctor together with the patient’s prescription record.
The second set of recommendations is by the American group Clinical Pharmacogenetics Implementation Consortium (CPIC).
The guidelines and recommendations for both DPWG and CPIC can be accessed at https://www.pharmgkb.org/guidelines.
These guidelines are evidence-based and there are now a growing number of double blind-trials that show not only better health outcomes, but significant reductions in health costs, by using pharmacogenomics to inform decisions.
Conclusion
Pharmacogenomic tests have been shown to work by a growing body of scientific evidence and cost-benefit studies. There are official guidelines that can be used to guide the results of these tests.
The tests can be accessed through doctors, specially trained pharmacists and, online. In Australia, the test costs $99. I am campaigning to make this available on Medicare (that is free). Can you help me and sign my petition?
If you have a history of adverse reactions to medication, or a hypersensitivity disorder, then your genes may just hold the answer. They certainly did for me.
NB* This blog post was extensively updated in August 2018, from a blog post in 2014.
Additional Reading
http://www.who.int/patientsafety/medication-safety/medication-without-harm-brochure/en/
Australian Centre for Health Research, Improving the Quality Use of Medicines in Australia, Realising the Potential of Pharmacogenomics, October 2008.
Deloitte, 2007, Targeted Therapies: Navigating the Business Challenges of Personalised Medicine, Deloitte Centre for Health Solutions, p 6.
https://cpicpgx.org/guidelines/ and https://www.pharmgkb.org/guidelines
https://www.tga.gov.au/publication-issue/medicines-safety-update-volume-9-number-2-june-2018#a2
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