Pharmacogenomics, Alison Vickery, Health, Australia

PHARMACOGENOMICS: DRUG INTOLERANCES AND GENES

August 07, 2018 10:00 pm

When you look in the dictionary under “drug intolerances and genes,” you will find my name.

I have written widely about adverse drug reactions‘ effects on my health. 

It started with being prescribed Metformin®, a medication for insulin resistance, resulting in my diagnosis of histamine intolerance.

Then a series of severe adverse reactions to medications saw me diagnosed with mast cell activation, chronic fatigue syndrome, sub-clinical Cushing’s Syndrome, and an acquired brain injury.

The mast-cell activation diagnosis was due to having less than 20% function of the CYP2D6 gene, with less than 20% function, meaning medicines that utilize this gene are toxic to me.

But a new world of pharmacogenomics has changed 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 correct dose for the individual.

While many factors can affect medicine safety, pharmacogenomics is often overlooked and profoundly impacts medicine safety.

So this is why it matters.

 

pharmacogenomics, drug intolerances, alison vickery, health, Australia

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 on the market work, but they don’t work in everybody.”

Simplistically, despite a system that works on “averages,” there are not many 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.

 

pharmacogenomics, drug intolerances, alison vickery, health, Australia

When Medicine Acts Promiscuously

This law of average approach also has several other problems.

When a medicine does not act as intended, increasing the dosage or adding additional medicine is standard practice. That is to guess.

Guessing can be a risky strategy where:

The dosage was too high, not too low for the individual.

The individual cannot use the medicine because they have too little function in that pathway, and alternative medicine would work.

Additional medicines interact (called poly-pharmacy). With every additional medicine, this risk increases, particularly over two medications.

It is difficult to stop the medicine.

Whenever a medicine does not act as designed, for example, pain killers do not address our pain, or anti-depressants make us even more depressed, we need to consider pharmacogenomics. 

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 warned that a significant number of medications cause severe adverse reactions, including suicide, including a broad range of antidepressants, attention deficit hyperactivity disorder medications, seasonal allergy medicines, smoking cessation medicines, and acne medicines.

Could this be due to pharmacogenomics? I hypothesize that this is especially so in people whose genes affect the availability and detoxification of medicines.

Notably, one study showed that patients who metabolize very slowly or fast have four times more disability claims than those with typical pharmacogenomic test results.

It seems to me to be barbaric to prefer to guess, particularly for high-risk medicines that cannot simply be withdrawn.

What if your doctor determined the right medicine and dosage from the outset? What if the wrong medicine in the wrong dosage led to a permanent disability?

histamine intolerance, masgt cell activation, medicines, Alison Vickery, Health, Australia

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 (mainly four essential 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 among 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.

The risk is significantly higher in other ethnic groups, including Asians, Pacific Islanders, and Africans. 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.

Please consider getting tested if your paternal or maternal family has a history of adverse medical reactions.

But why stop there?

The test has a lifelong application, so what if all children were tested at birth to get the right medicine in the correct dose throughout their life? It seems a small price to pay.

 

pharmacogenomics, drug intolerances, alison vickery, health, Australia

Pharmacogenomic Testing

Several pathology companies now provide genetic testing for how people react to drugs, including:

myDNA – this is who I used.

Genesight – in the USA. 

Importantly, 23andMe does not report the relevant genes due to regulatory limitations.  

Once you have your test results, you and your doctor must verify the genes used to process medication and select the most appropriate medication and dosage. 

Two key bodies have been working to develop pharmacogenomics recommendations. 

The pharmacogenetic Working Group of the Royal Dutch Association for the Advancement of Pharmacy (DPWG) has incorporated recommendations into the National Dutch electronic prescribing system. This system is being introduced in other European countries. 

The Clinical Pharmacogenetics Implementation Consortium (CPIC), whose recommendations are also being systematically reviewed and incorporated into America’s Food and Drug Administration’s guidelines.

The guidelines and recommendations for 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 showing better health outcomes and significant reductions in health costs, using pharmacogenomics to inform decisions.

 

Conclusion

A growing body of scientific evidence and cost-benefit studies have shown pharmacogenomic tests to work. We can use official guidelines to guide the results of these tests.

We can access the tests through doctors, specially trained pharmacists, and online. 

If you have a history of adverse reactions to medication, or a hypersensitivity disorder, then your genes may hold the answer. They certainly did for me.

 

To learn more about adverse reactions to medicines, check out my blog post,  The CYP450 Medication, Inflammation, and Histamine Connection.

Follow me on Instagram and Facebook to continue the conversation.

 

Additional Reading

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.

Australian Centre for Health Research, Improving the Quality Use of Medicines in Australia, Realising the Potential of Pharmacogenomics, October 2008.

https://acola.org.au/wp/pmed/

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

Winner JG, Carhart JM, Altar CA, Allen JD, Dechairo BM. A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med. 2013;16(89):219-27.

Singh AB. Improved Antidepressant Remission in Major Depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report. Clin Psychopharmacol Neurosci. 2015;13(2):150-6.

Perez V, Salvart A, Espadeler J, et. al. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder results of a randomized, double-blind clinical trial. BMC Psychiatry. 2017;17:250.

Elliott LS, Henderson JC, Neradilek MB, Moyer NA, Ashcraft KC, Thirumaran RK. Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial. PLoS One. 2017;12(2):e0170905.

Saldivar JS, Taylor D, Sugarman EA, Cullors A, Garces JA, Oades K, et al. Initial assessment of the benefits of implementing pharmacogenetics into the medical management of patients in a long-term care facility. Pharmacogenomics Pers Med. 2016;9:1-6.

Bradley P, Shiekh M, Mehra V, et al.: Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: a randomized clinical trial demonstrating clinical utility. J Psychiatr Res 2017; 96:100–10.