New Approaches Could Cut Adverse Drug Events

Utilizing many of the skills learned in pharmacy school could help to personalize care and enhance medication delivery for patients, potentially leading to reductions in adverse drug events and health care costs, according to a presentation by Calvin H. Knowlton, BScPharm, MDiv, PhD, at the 2019 NCPA Annual Convention.

"Community pharmacists can increase patient safety and revenue by putting science back into their practice," said Knowlton, founder, CEO, and chair, of Tabula Rasa Healthcare, Inc. "This means not just looking at 1-to-1 drug interactions but the mechanism underneath. Knowing a patient’s medication risk aids in personalizing a medication care plan."

Adverse drug events are the third leading cause of death in the United States, behind heart disease and cancer. There are 173,000 deaths per year related to adverse drug events, with 73,000 related to opioids alone. Some of the causes of adverse drug events are cognitive and functional changes in patients taking drugs with anticholinergic and sedative properties. Moreover, therapies interfering with calcium or potassium channels can cause cardiac issues, particularly QTc prolongation.

However, in some cases, adverse drug events are the direct result of competitive inhibition brought on by polypharmacy or prescription cascades. Knowlton noted that patients taking 7 or more medications have an 82% chance of having an adverse drug event. "And this does not include over the counter medications," he added. In the United States, 39% of seniors are on 5 or more medications, opening up a huge potential for events.

When dealing with multiple medications, there are science-driven strategies that can help reduce the risk of adverse drug events, Knowlton said. A simple cheek swab can reveal genetic information on an individual's ability to metabolize medications, which, when coupled with pharmacokinetics, pharmacodynamics, and chronopharmacology, could help improve the quality of care.

There are 10 to 12 genes that encode the enzymes that metabolize most medications, with some of the leading enzymes being CYP2C9, CYP2D6, CYP2C19, CYP3A4, and CYP1A2. However, not every individual has the genetics to encode all of these enzymes, calling for greater use of pharmacogenomics. "If we don't do a cheek swab, we would assume that everyone has normal metabolism," Knowlton said, adding that making assumptions is never good practice.

Even if a patient has genetics to indicate normal drug metabolism, the drugs taken can cause phenoconversion to a state of nonfunctional metabolism. Moreover, many drugs are metabolized by the same enzymes, causing backups and inappropriate absorption. This can lead to an increase in the dose at the physician level, which opens the door for an overdose, if the patient were to stop taking the competitive medication. To avoid this, the treatment could be changed to one that is metabolized by a different enzyme or by altering the time of day the dose is taken, to avoid competitive inhibition.

If medications are attempting to use the same gene/enzyme, and all the treatments have a similar affinity coefficient, the medication with a higher dosage will occupy the gene/enzyme first, Knowlton said. In an example, he noted that both metoprolol and diphenhydramine have a high affinity for CYP2D6, if 1 is given at 25 mg and the other at 50 mg the higher dose would be dissolved and circulate at full strength while the lower would have a diminished effect.

"This is low hanging fruit, but the only people who know this are pharmacists," Knowlton said.

Medical training for nurses and physicians does not include pharmacokinetics, pharmacodynamics, pharmacogenomics, and chronopharmacology, he noted, only pharmacists receive this training, making them the experts.

Potential for Cost Savings

In 2016, $450 billion was spent on prescription medications, and another $528 billion to address adverse drug events. While polypharmacy and prescribing cascades have led to adverse drug events, Knowlton noted that pharmacy benefit managers (PBMs) are partially to blame as well, since most PBMs only allow 2 drugs per class, based solely on costs and not metabolic pathways. Moreover, he noted that the payment models in the pharmacy space and existing software tools are out of date.

The better use of medication and pharmacy-patient consultations could help change the cost story. In an analysis of 200,000 patients in a CMS project, medication risk score (MRS), generated by a Tabula Rasa software solution, was found to correlate with average total cost and aligned closely with hospitalization. The software tool utilizes pharmacogenomic data to indicate which enzymes are present, while also showing information on the effectiveness of treatment, based on genomics, and other therapies being used.

An MRS of 10 correlated with a hospitalization risk of 26%, while a score of 20 or 30 had hospitalization rates of 44% and 64%, respectively. Moreover, CMS reported there was a cost savings that exceeded the 2% threshold established by CMS.

The CMS project now has 2 years of outcomes information showing consistent savings with the decision support tool, which is being marketed under the name MedWise by Tabula Rasa. The software is not currently covered by CMS, but that could change as more data become available. It can be found on the athenahealth Marketplace.

This article was updated on October 28, 2019.

REFERENCE

Knowlton C. New Ways to Identify and Mitigate Adverse Drug Events and Get Paid for It. Presented at: NCPA 2019 Annual Convention & Expo; October 26, 2019; San Diego, CA.