Despite its promise, PGx use remains minimal in most clinical settings. The six most common laboratory tests performed to assess drug safety are listed below. Notice that none of these are 'classic' CYP450 PGx tests. Instead, they are more specific tests to determine the risk for a single side effect. In the early 2000s, PGx test demand was predicted to grow exponentially. However, over twenty years later, it is clear that PGx testing remains somewhat esoteric. The reasons for this are many. One reason is that there are just too many variables at play with drug metabolism (diet, co-medications, age, organ function, etc.) to rely on a simple PGx result. With so many variables, the cost of obtaining a PGx genotype on a patient becomes hard to justify. As genetic test prices continue to fall, this will present less of a barrier in the future. Another problem has been the lack of clinical studies showing that PGx improves patient morbidity and mortality. If PGx testing does not lead to better outcomes, it is hard for clinicians and patients to justify its cost. Some studies suggest, for example, that PGx testing may reduce hospital admissions (for those on warfarin). Still, few large, influential studies demonstrate that PGx testing provides added patient benefits.
The United States Medicare/Medicaid system has also been slow to reimburse for PGx testing. Thus, it has not been adopted by clinical laboratories or health systems.
There are some drugs, however, for which PGx testing is becoming more popular. Some of these drugs have such a high potential for severe, lethal toxicity that PGx testing or enzyme testing for these drugs has become the standard of care. Some examples of these drugs and the enzymes that are assessed before use include:
- UGT1A1: (UDP-glucuronosyl transferase 1A1) Assessed to identify patients at risk of adverse drug reactions to irinotecan, atazanavir, nilotinib, pazopanib, and belinostat.
- TPMT: (Thiopurine methyltransferase activity) Predicts potential for toxicity to thiopurine drugs 6-mercaptopurine, 6-thioguanine, and azathioprine.
- DPD: (Dihydropyrimidine dehydrogenase) Identifying individuals at increased risk of toxicity when considering 5-fluorouracil and capecitabine chemotherapy treatment.
- HLA-5801: 6–7% of Asians have a mutation in the HLA-5801 gene, which gives hypersensitivity to the drug allopurinol. Stevens-Johnson syndrome or toxic epidermal necrolysis can occur in susceptible patients. The presence of the HLA-B*58:01 allele is strongly associated with these adverse conditions.
- HLA allele B*1502: This is a marker for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. The FDA now recommends genotyping all Asians for the allele.
- HLA-B*57:01: Used to identify individuals with an increased risk of hypersensitivity reactions to abacavir (a drug used to treat HIV). The drug is not recommended in people positive for the allele.
Clopidogrel (Plavix) is another drug for which testing is sometimes conducted. Although CYP2C19 testing can be done to predict the patient's response, platelet testing is more common. Since clopidogrel is an anti-platelet drug, platelet function can be directly assessed to ensure that the patient can convert clopidogrel to its active metabolite to achieve the needed anti-platelet effect.
