When Genes Point to the Right Medicine

Known as pharmacogenetics, this form of precision medicine enables doctors to prescribe codeine only after genetic testing shows the medication will be safe and effective for that person.

“Having sickle cell and trying not to have a pain crisis is always on your mind, 24/7,” says Justin, now 22. “When you do anything, the first thing you think is, ‘Do I have my medicine with me?’ More times than not, the codeine helped.”

Personalized care

St. Jude has long been a leader in pharmacogenetics, the study of how a person’s genes influence which medications and doses will work best or may cause dangerous complications. Research has shown that about half of all hospitalized patients each year may receive drugs that, because of the recipients’ genetic makeup, could lead to serious side effects.

For more than two decades, pharmacogenetics has guided the use of chemotherapy in St. Jude patients treated for leukemia. The hospital is one of only a handful of institutions to offer pharmacogenetics testing to patients as standard care.

Since 2011, all new St. Jude patients have been screened for variations in 230 genes, including one called CYP2D6. This gene plays a pivotal role in how patients respond to codeine. The screening tests also determine responses to other drugs. These include certain chemotherapy agents as well as medications for nausea, depression and infections.

Codeine’s widespread use in pediatric patients has been questioned in recent years. Nationwide, several children who received it for post-surgical pain relief died. These deaths were later linked to CYP2D6 variations. After a warning by the U.S. Food and Drug Administration, some hospitals suggested ending all codeine use in children. Several pediatric hospitals removed the medication from their list of approved drugs.

But St. Jude is using personalized medicine to identify patients most likely to benefit from the drug, while avoiding codeine use in patients who are likely to experience side effects. Clinicians make sure codeine is given only to children whose genes indicate it will likely be safe and effective. About 12 percent of the general population carries CYP2D6 variants that drastically alter how their bodies process codeine. 

A model for others

Why is codeine such an important pain relief option?

Over-the-counter ibuprofen is often not strong enough to alleviate sickle cell pain crises. Codeine alternatives include oxycodone, hydrocodone, fentanyl and morphine—expensive and tightly regulated drugs that doctors can’t prescribe over the phone.

“There are a lot of really good and practical reasons to keep codeine around,” explains Kristine Crews, PharmD, of St. Jude Pharmaceutical Sciences. “It’s inexpensive. It’s oral, so it doesn’t require an IV.

“Our sickle cell doctors felt strongly that codeine should remain a choice because we have a lot of experience with it,” she continues. “Access is greater because it can be called in to a pharmacy without necessarily a written prescription, and it works well in most patients. And with pharmacogenetic testing, we can know up front which patients should not receive codeine, keeping it an option for the majority of patients it is likely to help.”

Crews joined Jane Hankins, MD, of St. Jude Hematology, to head a research project—the most comprehensive of its kind. Published in the journal Pediatrics, the study tested 621 St. Jude sickle cell patients to determine their CYP2D6 status. About a third of the patients required significant pain relief during the study period.

Researchers found that in just over 7 percent of the patients, their bodies broke down codeine to such a great extent that even a small amount might result in a fatal overdose. Another 1.4 percent had the reverse problem. These patients inherited no working CYP2D6, so codeine could not be processed at all. That meant the drug was unlikely to help. 

Mutually fulfilling research

Medical alerts embedded into the St. Jude electronic medical record prevent any child with high-risk codeine status from receiving the drug. The model serves as a beacon to other health care systems on how pharmacogenetics can enhance drug therapy for any pediatric patient group coping with chronic pain.

“We wanted other people to realize they can safely get the drug to the patients who need it by using pharmacogenetics,” Crews says.

The results will last a lifetime.

“Your genetics don’t change,” Crews notes. “We tell patients to share the information with their doctors and providers outside of our system when they outgrow St. Jude.”

In related work, Kelly Caudle, PharmD, PhD, and James Hoffman, PharmD, of St. Jude Pharmaceutical Sciences, recently led a national panel working to establish a common vocabulary surrounding pharmacogenetics.

Published in Genetics in Medicine, the group agreed on standardized terminology to describe how gene variations affect function and clinical care. Their goal is for all institutions to use the same language to report test results. The aim is to expand the use of precision medicine.

Hankins and Crews feel gratified to help improve pain management in sickle cell patients, whose frequency of pain crises tends to increase as they get older.

“Pain crises are very difficult because they really interrupt the kids’ lives,” Hankins says. “They’re at school and the pain comes unannounced and they have to go home. It stops everything.

“Knowing I’m doing research that’s helping me treat them better is fulfilling to me and reassuring to them,” she continues. “It makes me feel I’m having an impact in moving the field forward.” 

From Promise, Autumn 2016