Genetically personalized Coumadin therapy (Warfarin)

Is personalized medicine (pharmacogenomics) the future of drug therapy?

Medication provides treatment for many diseases and affects our body’s physiological function in various ways, but they have one major downside – the difficulty of matching a drug to a specific patient. Most drugs are identical for all patients.

Drug dosage can be adjusted according to criteria such as sex, age, weight, and disease severity. However, these adjustments do not usually take each patient’s personal makeup into consideration. Each of us carries a unique genetic profile, our genes are coded to different proteins which may affect the way we break down drugs and react to drug therapy.

What is the solution to this problem? Pharmacogenomics, also known as personalized drug therapy, may provide answers to this challenge. Knowing which genes affect a patient’s reaction to a drug and testing these genes can help predetermine the effect of that drug on patients with greater accuracy.

Personalized medicine provides tools for effectively tailoring treatment to each patient, unlike the “trial and error” approach usually taken when choosing drug dosages. Drug personalization uses not only factors such as age and weight, but also each patient’s specific organ system function, and their personal genome.


Coumadin – a useful drug with various side effects

Warfarin, sold under the name Coumadin, is a common drug among older patients. Coumadin is an anticoagulant; it helps treat the formation of blood clots and is commonly referred to as a “blood thinner”.

Coumadin is prescribed in cases of a risk for thrombophilia (abnormal blood coagulation), especially for treating atrial fibrillation. 

Atrial fibrillation creates a risk for blood clots in the heart, these blood clots may reach the brain and cause a stroke. Coumadin therapy helps reduce the risk for strokes in patients with atrial fibrillation.

Despite Coumadin’s effectiveness, this drug is associated with various side effects. One of the major risks of Coumadin usage is uncontrolled bleeding, which may be life-threatening. In addition, it is difficult to monitor the levels of this drug in the blood, regular blood tests are required for adjusting drug dosage. Moreover, patients’ reaction to this drug vary greatly – while some patients require a low dosage, others only react to higher dosages.

The common method of prescribing Coumadin today is by starting with a low dosage and adjusting dosage according to blood test results, until reaching a stable coagulation ratio.


Personalized coumadin treatment

Research published in The New England Journal of Medicine tested the effect of genotype-guided dosing in Warfarin therapy. 

The trial involved 455 patients with venous thromboembolism or atrial fibrillation. All patients underwent genetic sequencing of genes linked to Warfarin metabolism in the liver (CYP enzymes).

Patients were randomly divided into two groups. Patients in the first group received a standard loading-dose of Coumadin, while patients in the second group received Coumadin dosages determined by pharmacogenetic-based tests. After an initial period, all patients received the standard dosage according to routine practice.

Research results indicated a substantial advantage for the genotype-guided group. This advantage was expressed in three main parameters. The time in the therapeutic INR range was 67.4% in the genetic-guided group, compared to 60.3% in the control group. These low percentages indicate how difficult adjusting drug dosage can prove.

In addition, the time patients took to reach the therapeutic ONR was 21 days in the genetic-guided group, compared to 29 days for patients in the control group. The number of cases of abnormal anticoagulation resulting from treatment (because of excessive dosage) was significantly lower in the genome-guided group.

Personalized medicine’s role in the future of drug therapy seems promising. In the near future, more patients may receive treatment after undergoing genetic testing of genes related to optimal dosage of drugs. This approach will lead to a more efficient treatment.

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