Column Author: Tracy Sandritter, PharmD, BCPPS | Clinical Specialist, Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation; Adjunct Professor, UMKC School of Pharmacy.
Alexa Pagano, MD| Assistant Professor of Pediatrics, Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation
Column Editor: Amita Amonker, MD, FAAP | Pediatric Hospitalist | Assistant Professor of Pediatrics, UMKC School of Medicine
Background: Have your patients asked about testing to see which medication will work best for them? Pharmacogenetic (PGx) testing is rising in popularity among patients and providers. While many parents are willing to use a medication for their child to treat illness, parents are often worried about potential side effects and don’t want to “experiment” with different medications without first knowing if that medication will work.
For some children, it can take a while to find the “just right” dose of a medication. PGx is a type of precision medicine that factors in a child’s unique genetic makeup to guide medication dosing. This information can help tailor their treatment to maximize benefit while minimizing risk.
One study of 802 medically complex children found that 68% were prescribed at least one medication with an established PGx association. In those who had PGx testing, 48% had genetic variants with established drug-gene guidelines for one or more of their current medications.1 In a 2022 systematic review, 71% of studies evaluating the cost of pharmacogenetic testing for drugs with evidence-based guidelines determined that PGx testing was cost-effective or cost-saving.2
It’s easy to see how this type of precision medicine is appealing for families, but what can PGx really tell us, and how is it being used today?
Pharmacogenomic Considerations: Many different genes relate to medication efficacy and safety. First, you need enough medication in the body to reach the intended drug target. Additionally, that medication must be a good fit at the intended target (receptor).
The receptors medications bind to are encoded by a patient’s DNA. Ideally, providers could look at a patient’s DNA and predict which medication within a drug class would fit most precisely into that patient’s receptor and thus be most effective. Unfortunately, it’s not that simple. Sometimes multiple receptors are involved in medication efficacy, such as the multiple receptors involved in serotonin signaling. Sometimes interactions at unintended receptors can lead to unforeseeable adverse reactions. Currently, there is not enough high-quality evidence to determine which medication will fit most precisely. Many studies have begun to evaluate the efficacy of medication based on PGx data at the receptor level, but the quality of evidence is low at this time. Some pharmacogenetic test panels include pharmacogenetic receptor data (e.g., serotonin receptors) in their results, but these data haven’t yet reached a stage where this information can be used clinically.
However, the other component that drives medication efficacy is having a sufficient amount of medication in the body. This component is driven by both the dose of the medication and how well the body metabolizes the medication. There are multiple types of enzymes in the liver that metabolize medications such as the cytochrome P450 system (CYPs) and UDP-UGTs. Knowing how fast or slow a patient metabolizes a medication can guide providers in determining the correct dosage. PGx testing can test some of the most common enzymes that metabolize medications. High-quality evidence guides dosing of medications based on pharmacogenetic results of many metabolizing enzymes.
If a patient is not responding to a medication, it might be due to ineffective medication fit at the drug target or too low a dose. Or in a patient with adverse effects, the side effects may be due to slow metabolism with dosages that are too high for that patient. PGx knowledge enables providers to rule out the variable metabolism when the patient is not responding to a medication (receptor interactions) or is having adverse effects.
Finally, HLA testing is available for some medications to assess risk of severe allergic reactions. This testing applies only to certain medications such as carbamazepine, abacavir and allopurinol.
Groups such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) as well as others examine the existing research and data on genes, variants and medications to develop evidence-based guidelines for medication-based PGx information.
PGx testing can be helpful in many subspecialties. Some examples include mental health (selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, atypical antipsychotics, mood stabilizers, atomoxetine), gastroenterology (proton pump inhibitors), cardiology (statins), oncology, pain management, transplant medicine (tacrolimus), and infectious diseases (HIV and HCV treatment, voriconazole).
Pharmacogenetic testing options: Many companies offer pharmacogenetic testing (e.g., Genesight, OneOme, RPRD). Not all companies are the same even though they may test for similar genes. Companies may not test for the same gene variants; thus, different companies may produce different results for the same gene in the same patient. Some companies include genes on their test results even if current evidence for use of that gene in precision medicine is lacking. Prices for testing can vary widely, from $200 to nearly $1000. Some companies will bill insurance and others won’t. It’s important for providers to consider these factors when choosing what company to use. Conveniently, most companies use DNA obtained from a buccal swab that patients can do themselves. Most companies will ship the test kit to the patient’s home, and patients mail their sample back to the company.
The GOLDILOKS® Clinic: We are a multidisciplinary team available to answer provider questions regarding pharmacogenetic testing, adverse drug reactions, failure to respond to therapy, and drug-drug interactions. We provide telehealth appointments, which increases access to patients.
References:
- Pan A, Scodellaro S, Khan T, et al. Pharmacogenetic profiling via genome sequencing in children with medical complexity. Pediatr Res. 2023;93(4):905-910.
- Morris SA, Alsaidi AT, Verbyla A, et al. Cost effectiveness of pharmacogenetic testing for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: a systematic review. Clin Pharmacol Ther. 2022;112(6):1318-1328.
