Disclaimer: The following information is for education only and not to be taken as medical advice!
How Pharmacogenetics can improve medication efficacy and safety in Hyperemesis Gravidarum
The practice of prescribing medicine based on a person’s DNA to ease or potentially cure disease states, commonly known as pharmacogenetics, started decades ago, yet current utilization is only touching the surface. The phrase “Personalized Medicine” is both a science and an art, has many synonyms and may have more than one meaning. Pharmacogenomics looks at the entire genome while pharmacogenetics, where I specialize, focuses on a segment of DNA. While personalized medicine also encompasses looking at a person’s genetic code for risk of certain disease states, as is the case in non-invasive prenatal testing (NIPT), many pharmacists are now specializing in interpreting these DNA variations to optimize medication management.
Pharmacists spend their careers applying the pharmacokinetics and pharmacodynamics of medications to guide medication safety. Pharmacogenetics takes this understanding to a patient specific level. The test is an easy cheek swab which gets sent to a lab. The results tell us which variation of an enzyme the patient has. The clinical interpretation of these results by a pharmacist with or without the support of translational software or artificial intelligence (AI), help guide the dosing and duration of a medication to improve efficacy and safety, allowing informed decisions to be made.
In some disease states, including oncology, psychiatry, cardiology and pain management, personalized medicine is leading the way to optimal therapy, yet it’s just about completely absent from maternal health care. In fact, Dr. James Alexander, a maternal fetal medicine specialist and Chairman to the OBGyn Department at the Kirk Kerkorian University of Nevada, Las Vegas, School Medicine, told me that the practice of obstetrics is decades behind that of oncology where it is now a standard of care to use personalized medicine when treating cancer patients.
As our genes do not change, you only need to have the test done once in your lifetime, and the results can be applied to medications you prescribed in the future. You can help improve medication safety by educating your provider and asking to have the test done. The simple test can even be done at home and mailed to the lab. It’s time to make it a standard of care in maternal health!
HG Medications with PGx Variations
Take a look at some of the medications with pharmacogenetic variations that support women suffering with Hyperemesis Gravidarum:
The Genes behind the Medications with PGx Variations
- CYP450 enzymes:
- Histamine-2 Receptor Antagonists (H2RAs) and Proton Pump Inhibitors (PPIs) are predominantly C219, but also 1A2 and 2D6
- Ondansetron (Zofran) and granisetron (Kytril, Sancuso) has many pathways within the CYP450 system
- Methylprednisolone, prednisolone and prednisone have ABCB1 gene transporters
- Ondansetron (Zofran) are also transported by the ABCB1 gene transporters
- MTHFR gene variations contribute to how much folic acid is absorbed, along with other vitamins. The CDC recently added a page to their website discussing the effects of MTHFR variations on folic acid. If you have a variation that is known to not be metabolized, speak to your doctor about taking a l-methyl folate supplement instead of folic acid.
- MMADHC is known to play a role in B12 metabolism. With this mutation, speak to your doctor about taking methylcobalamin instead of cyanocobalamin.
- Many more!
(*MTHFR and MMADHC does not have clinical evidence showing any direction connection to HG but may affect other conditions in the mother and baby)
Four Enzyme Variations
Enzymes are proteins that make chemical reactions happen. In the case of PGx, each of us will have one of four variations of the enzymes needed to metabolize medications. The enzymes literally break down the medication in the body so that the active ingredient can get to the site of action and result in the needed effect. On one end, in the ultrarapid metabolize, the medication will move too quickly through the body with less, if any, active ingredient available to work. On the other end, too much of the medication stays in the body often resulting in adverse effects. These four variations are called:
Looking at one medication and one variation, however, is only the beginning of putting the puzzle pieces together on choosing mediations to optimize the benefit while minimizing risk of adverse effects. We then look at much more including transporter variations and other drug-drug interactions. For example, if you are taking two medications with the same pathway, one may inhibit the other from metabolizing. Combine that with an understanding of the kinetics of the medication along with the patient’s other disease states, we come up with a clinical decision on the safest medication option and at which dose to start.
Take a look at my personal results for ondansetron (Zofran) and granisetron (Sancuso). According to the AI of my personal ondansetron results, the transporter variation I have can actually INCREASE my likelihood of nausea and vomiting. 😯 This is where human knowledge outdoes artificial intelligence!
Believe the patient!
Another reason having PGx results is powerful is seen in the following results of a mom who survived HG yet desperately wanted to have another child. During her first pregnancy, she was not believed when she said that ondansetron was not offering relief. Having the results in black and white offers validation and dismisses the notion that the it’s all in our head, as women have been told by doctors for centuries.
PGx and Comprehensive Medication Management (CMM)
According to the CDC, in 2019, 19.2% of the US population are on mental health medications and from 2015-2018, 10.7% are on pain medications, and these numbers have only increased since that time. Now imagine the women in these categories becoming pregnant and being taken over from HG. PGx is the perfect place to optimize their medications, yet I still am hearing obstetricians telling their patients that all the moms take sertraline for depression while pregnant or lexapro for post partum depression.
Recommendation: If you have had miscarriages without an explanation, I recommend asking about genetic testing for clotting disorders an MTHFR mutations. Your doctor can then prescribe a medication to prevent blood clots.
Why is there hesitation?
I believe there a few blocks to PGx becoming a standard of care:
- Provider belief in the science
Changing a standard of care takes decades. For some providers, they do not see a need for improvement in the way they prescribe medications. As in the depression example, many provider always prescribe the same medication for all their patients with the same diagnosis and are not open to believing there is a better method now available.
- Variation in lab methodology and lack of clinical interpretation by a certified doctor
I have heard from providers who said that they tried it and did not see any benefit. If this happened, it is likely due to variation in testing methods among the labs doing the test along with a lack of a comprehensive understanding on how to apply the results. For example, ondansetron has a major pathway and many minor pathways along with many drug-drug interactions. If a lab only looks at the major pathway without considering the other possibilities, the results many not be accurate, and the clinician may be unwilling to spend time utilizing PGx results in the future. Also, for this reason, I do not recommend paying for direct to consumer tests.
While a decade ago, the test was in the $1000s, out of the price range for most patients. Fortunately, today it is affordable for most patients, even when not covered by insurance.
Dr. Alexander would happily set up a study at his department at UNLV but unfortunately there is no funding to pay for the test or a consultant trained in interpreting the results. Once again, it is up to the patient to advocate for this test to be done prior to starting medications. If you are on mental health or pain medications already, insurance may cover the cost of the test, but the doctor who is prescribing the medications will need to be the one to order it. If you are interested and do not have insurance that covers it, I offer a self-pay version of a complete panel for $429.00.
Personalized Medicine is now experiencing a revolution!
The revolution to improve medication efficacy and patient safety through the science of pharmacogenetics has finally begun. With medication errors a top cause of death according to some studies, providers are now understanding the power behind pharmacogenetic results. What’s driving the change? Practitioners of oncology have embraced personalizing medicine, along with those in pain management as they try to curb the opioid epidemic and psychiatrists which has many medications have the same indications.
In addition to ease of testing through accessibility and affordability, the landscape in cardiology saw monumental change in 2021. At the same time that a study was published in the journal Nature supporting cardiologists use of pharmacogenetic testing for clopidogrel, warfarin and statins, the state of Hawaii won a lawsuit against the makers of Plavix because the companies knew the medication is not effective in Pacific Islanders yet promoted it equally there as it did in areas with other patient populations.
Now is the time for personalized medicine through the use of pharmacogenetics to become a standard of care in maternal health too!
For more information
✔️ Share this blog by Invitae, the lab I use, with your doctor: What is Pharmacogenomic PGX Testing and Why Would I Benefit?
✔️ For those in the UK, Super Pharmacy is partnering with your government to start a PGx program.
✔️If you had a PGx test done, please share your experience in my FB support group
Order your test now!
Contact me at info@HGPharmacist.com to partner with your doctor!