Clopidogrel and genetic testing for drugs: Is it necessary?
When one of your friends, family or well-wishers suffer from a brain stroke due to bleeding, whom or what do you suspect ? It would be a mystery unless a doctor performs an autopsy on the patient. What if one can prevent brain stroke even while consuming blood thinning drugs such as Clopidogrel (by the way is a major cause of stroke due to bleeding ) beforehand ?
It is possible when the patient, even before taking clopidogrel, gets tested for drug efficacy with pharmacogenomics testing such as MedicaMap.
What is in the name?
Clopidogrel is a medication used to decrease one’s risk of heart and brain disease due to blood components known as platelets. Platelets stick with one another forming clumps which clog the arteries thereby reducing blood supply to vital organs such as heart and brain. It is mostly prescribed to patients who underwent stenting in the heart to prevent blockage. Clopidrogel comes as a tablet to take orally and its efficacy will last for five days.
Drug interaction: a matter of enzymes
Clopidogrel transforms into various compounds inside the body due to various enzymes. These enzymes are known as cytochrome P-450 (CYP). They are produced according to genes present in DNA. Now these enzyme producing genes are not the same in each individual. Different genes produce different enzymes. Some enzymes transform clopidogrel drugs in such a way that some individuals have reduced enzyme function and some have increased enzyme function leading to various levels of efficacy.
The following table shows genes associated with cytochrome P-450 (CYP) enzymes.
The numbers with stars are different variants of the same gene and are known as star alleles. DNA sequence variations in genes, alters proteins, which are notified as star alleles and is directly proportional to a person's drug response. Star alleles are discovered and analyzed in Medicamap, a go-to product for pharmacogenomics in India.
Personalising medicine: an emerging practice
In Pharmacogenomics, personalising medicine according to a person’s DNA is the key.
A sure shot way to make it happen is through Medicamap. It is a cutting-edge pharmacogenomic test, which analyses an individual's response to medicines, based on his/her genetic makeup. From tolerance to risk of adverse reactions, this unique genetic testing kit uses highly validated genetic markers to analyse an individual’s drug-response profile based on their genetic makeup for 100+ drugs across specialties.
How does it work?
As the first step, a blood sample of the patient is taken for DNA sequencing.It shows the types of alleles present in DNA for that particular enzyme. This combination of alleles makes drug metabolism different for different people.
The following table shows the drug absorption according to clopidogrel metabolism. So every patient is divided into different categories based on their ability of drug absorption, according to the DNA read of that particular drug. Some are categorized as EM extensive metabolizer, IM intermediate metabolizer, PM poor metabolizer and UM ultra-rapid metabolizer.
Patients who are categorized as extensive, intermediate and poor metabolizers have the efficacy of clopidogrel decreasing in order. Poor metabolizers need an increased number of doses/dosages to attain the same efficacy as extensive metabolizers. Majority of people are extensive metabolizers. Extensive metabolizers need a normal range of dose decreasing the adverse effects of clopidogrel.
Poor metabolizers are prone to the negative effects of drugs even at the normal range of dose/dosages. According to CPIC (Clinical Pharmacogenetics Implementation Consortium) guidelines, adverse effects include brain stroke, heart attack and stent blockages. CPIC provides evidence-based clinical practice guidelines for pharmacogenetics implementation, and assigns clinical actionability to gene/drug pairs. This research led FDA to add blackbox warning on drug labels for doctors to advise alternate drugs for poor and intermediate metabolizers.
Medicamap: A precise genetic testing
This is why a precise genetic testing is necessary.Medica Map detects poor and intermediate metabolyzers. It acts as a prescription testing for drug advice.
Genetic variation leads to different levels of drug metabolism leading to different dosages and different adverse effects. Hence,every patient consuming clopidogrel should undergo genetic testing before personalizing the drug’s dosage. Personalized medicine is the way to go !
1. Cytochrome P-450 Polymorphisms and Response to Clopidogrel (N Engl J Med 2009; 360:354-362)
3. CPIC guidelines : https://files.cpicpgx.org/data/guideline/publication/clopidogrel/2022/35034351.pdf
4. Clopidogrel Pharmacogenetics — Why the Wait? (https://www.nejm.org/doi/full/10.1056/NEJMe1911496)
5. Clopidogrel Pharmacogenetics : State-of-the-Art Review and the TAILOR-PCI Study (https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811)