Personalizing Prescriptions with Pharmacogenetics

By: Toni Shears

When she was in pharmacy school earning her PharmD in 2014, Amy Pasternak encountered a professor who taught a class in personalized medicine. At the time, she believed she was learning the medical approach of the future. 

But in her residency the following year, Dr. Pasternak encountered pharmacogenetics — and realized that tailoring prescribed therapies to the patient’s unique genetic makeup was already in practice.

Today, as a Clinical Assistant Professor at the College of Pharmacy and a clinical pharmacist with Michigan Medicine, she leads the integration of pharmacogenetic information into patient care and prescribing practices throughout the medical center. She collaborates with different clinical teams to raise awareness of genetic variants associated with an atypical response to a particular medication.

“We want to make sure care teams know that there is a genetic marker that’s very important to a given medication from a safety or an efficacy perspective and make sure that all patients are tested for this genetic finding before we prescribe certain medications,” says Pasternak, a Clinical Assistant Professor of Pharmacy at the College.

When a patient has already been tested and the genetic marker is logged on the medical record, “we want to make sure we take the relevant intervention of personalizing treatment” – either avoiding the medication or adjusting the dosage to minimize adverse reactions, she says.

“One of the things I really enjoy about pharmacogenetics is it touches all areas of medicine. It’s not necessarily specific to one area, although I spend more time in oncology and transplantation,” she says. Psychiatry and cardiology are other areas where genetic variants pose a significant safety risk for certain drugs. “In those clinical groups, we have evidence that using genetic information can improve drug selection and positively impact patient response,” she says.

Demystifying Genetic Testing

As a clinical pharmacist, she sometimes provides pre- and post-test patient consultation. “We talk to them about the pros and cons of genetic testing, what the testing process is like, any medications they may have struggled with in the past, what type of medications they may need to treat their conditions in the future, and what complications they might see. Based on that, we can recommend appropriate laboratory tests that would help monitor those complications,” she explains.

“We also frequently counsel them about the cost of the testing process because, unfortunately, it’s not always covered by insurance. When the results are returned, we’ll often meet with the patient again to go through what those test results mean. 

“We highlight the findings that could impact current medication decisions, as well as key things to keep in mind for the future. If there is a significant safety risk for a medication, even if there’s no indication that the patient will receive that drug, we will still inform them. That way, if it is ever prescribed in the future, they are aware and it’s flagged in their chart.”  

Systemizing Genetic Testing

More often, Dr. Pasternak consults with care teams and informatics specialists, seeking ways to build details about pharmacogenetic risks into systems and processes so care teams are alerted to potential issues with a drug automatically. “The goal is to make this information accessible to every user in our system without having them go through intensive, specific genetic training,” she says. 

For medications that require genetic testing to prevent an adverse reaction, Dr. Pasternak has helped to implement flags and alerts in the medical record system that will prompt a search for test results when that drug is prescribed. If no genetic test is on file, the prescriber is notified to order the test. If the test is on file and the results indicate high risks with the drug, the prescriber is notified with recommendations for an alternative or information on how to proceed.

“We work with each individual clinical team to figure out which method and combination of flags, pop-up alerts, or automatic adjustments of the prescription in the background will be the most valuable to them in their existing workflows,” Dr. Pasternak explains. “We always try to provide the background check of the genetic result and if we find something where there’s an opportunity to make a personalized treatment decision, we notify the provider of that.”

Sifting Biodata for Links to Different Drug Responses

Dr. Pasternak also conducts research for genetically informed prescribing. She regularly taps into the Michigan Genomics Initiative’s (MGI) biodata — a research repository of DNA from more than 100,000 Michigan Medicine patients paired with their medical records — hunting for patterns in drug reactions that may be linked to a particular genotype. 

“Sometimes we have medications where we know there’s a lot of variability in patient response, but we don’t know why,” she says. “I have a couple of discovery projects where we’re looking at MGI to see if we can find a genetic marker related to the drug metabolism or something else that helps explain why we’re seeing these differences in patients’ responses.”

This type of analysis offers rich potential for enhancing clinical care. For example, she collaborated with Jeong Park, MS, PharmD, a Clinical Professor of Pharmacy at the College and a clinical pharmacist in the transplantation service, to analyze differences in patients’ responses to immunosuppression based on their genotype. They confirmed a genotype correlated with how a patient’s body will break down tacrolimus, one of the immunosuppressants they must take. 

Their results have not yet been published, but they leveraged this finding to make a case for genotyping kidney transplant patients to customize their post-transplant therapy. At their recommendation, Michigan Medicine has implemented genetic testing for every adult kidney transplant patient — an example of the real-world impact our clinical pharmacists are making.

This allows the care team to personalize the tacrolimus dosage based on genotype. Now, with that initiative in place, they can compare the outcomes for transplant patients with genotype-guided therapy to those who received standard care when clinicians did not have access to their genetic profile.

“We have a really unique opportunity to have a pre-post comparison of what impact the genetic testing is having in a large cohort, which is something few others have been able to do,” Dr. Pasternak says. It can be really challenging to do these prospective studies for pharmacogenetics, either for ethical issues or the small number of patients with specific variants.”

As ongoing research reveals more genetic differences in drug responses, Dr. Pasternak’s efforts to share this knowledge and build it into health information systems is vital. Flagging drugs that require genetic testing or automating recommendations for medications of dosing based on genetic testing — along with the welcome addition of Medicare and Medicaid coverage of pharmacogenetic testing in Michigan  —  moves personalized prescribing closer to becoming the standard of care. 

“We’ve really worked hard to start integrating genetic considerations into prescribing workflows so that our clinicians and patients don’t have to remember if they have had genetic testing years before. Testing or adjustments to the prescription will just be automatically recommended and provided to them at the point when a relevant interaction exists.”