The goals of pharmacogenomics are to prevent adverse drug reactions and maximize drug effectiveness for individual patients. Pharmacogenomic studies are performed in populations of subjects treated with a specific drug to identify genetic variants that predict drug response and the occurrence of adverse reactions. Once identified and validated, a genetic variant is incorporated into a diagnostic test that will predict a patient’s response to a specific drug. Pharmacogenomics can improve the benefits and reduce the risks of medications by determining what patients are most likely to respond favourably to a specific medication and by predicting what individuals are at greater risk for an adverse drug reaction. This information can be used to adjust an individual’s dosage according to their likely response to treatment.


Is Pharmacogenomic Testing Used Currently in Clinical Practice?

Yes. Pharmacogenomics research has led to several genetic tests that provide clinical dosing recommendations.

Irinotecan, an anticancer drug, is associated with severe and potentially fatal diarrhea and neutropenia in 20-35 per cent of patients. A specific variant in the UGT1A1 gene reduces the inactivation of irinotecan metabolite and therefore increases the risk of the ADR. In 2004 the Irinotecan label was modified to indicate the role of UGT1A1*28 polymorphism and recommendations for lower starting doses in patients homozygous for the polymorphism.

Azathioprine has been used as a first-line therapy for cancer and autoimmune diseases for over 50 years. Variants in the thiopurine methyltransferase (TPMT) gene reduce the inactivation of azathioprine, leading to severe or fatal myelosuppression and infection in homozygous carriers of these variants (0.5-1 per cent of people). Azathioprine-induced toxicity can be avoided with TPMT genotyping and in 2003 the FDA revised the azathioprine label to inform clinicians about increased risk of severe myelosuppression for TPMT activity-deficient genotypes and to provide TPMT testing options.

Warfarin is the most commonly prescribed oral anticoagulant drug in the USA with an estimated 2-million people taking the drug. but the Finding the ideal patient dose is challenging; too high a dose may lead to serious risks of excessive bleeding and intracranial haemorrhage (affecting 5-35 per cent of patients), while a sub-therapeutic dose may lead to the dangerous formation of blood clots (affecting 1-8 per cent of patients). Variants in the CYP2C9 and VKORC1 genes account for 57-63 per cent of variance in warfarin dose, and in 2005 the FDA revised the warfarin label with recommendations for pharmacogenetic testing. The average cost per warfarin-induced bleeding event is $15,988, and warfarin pharmacogenetic testing would save an estimated $1.1 billion in U.S. health care spending each year, while preventing 17,000 strokes and 85,000 serious bleeding incidents.

Pharmacogenomics is also becoming more common in drug development. Currently there nearly 80 phase II and III clinical trials collecting genomic DNA samples for pharmacogenomic purposes.