Mixing 2 Common Drugs May Be Deadly for Diabetics

Pharmacists should keep an eye out for patients with diabetes taking pravastatin and paroxetine concomitantly, as this medication combination could be deadly.

Although pharmacists are already aware of common drug-drug interactions such as warfarin/diflunisal and methotrexate/probenecid, studies have shown that only 67% of serious drug interactions spark a correct warning from a pharmacy computer system with such alerts.

Discovering drug interactions is difficult partly because large clinical trials are often primarily focused on establishing the effects of a single drug. In many cases, the study cohort is too small to observe potential side effects of a medication in certain populations.

In light of this, the FDA heavily relies on pharmacists and other health care providers to consistently report adverse drug events (ADE) through its Adverse Event Reporting System (AERS).

Consistent reports allow the system’s algorithms to detect common drug interaction-related adverse events. On the other hand, AERS can fail to detect less frequent interactions when related ADE reporting is sporadic.

Teresa Rubio, PharmD, of the FDA’s Office on Health and Constituent Affairs, previously described to Pharmacy Times why reporting ADEs to the FDA is crucial.

The Chicago Tribune in conjunction with data scientists, pharmacologists, and cellular researchers at Columbia University Medical Center developed a separate algorithm based on an analysis of aggregate side effects that mined data from AERS to weed out dangerous drug combinations with diabetes-related effects.

Using the AERS and patient electronic health records, the research team found that 2 of the most commonly prescribed drugs in the United States—the cholesterol buster pravastatin and the antidepressant paroxetine—were associated with “significantly higher” blood glucose levels when administered together.

The number of patients who may be currently taking this medication combination is considerable. In 2009 alone, 15 million and 18 million prescriptions were written in the United States for paroxetine and pravastatin, respectively, the researchers found. To add to that, 30 million individuals worldwide are estimated to have depression, and 100 million individuals are estimated to have hypercholesterolemia.

Additionally, the US Centers for Disease Control and Prevention has estimated that more than 29 million individuals in the United States have diagnosed or undiagnosed diabetes. Another 86 million are estimated to have prediabetes, which increases the risk of developing type 2 diabetes, heart disease, and stroke.

Diabetics with unexplained, prolonged spikes in their blood sugar may eventually develop hyperglycemia and diabetic ketoacidosis. Although the overall mortality rate for the latter condition is less than 2%, prognosis worsens in older patients who have severe intercurrent illnesses, or if treatment is provided outside of an intensive care unit.

The study authors stressed “it is important to evaluate whether this effect extends to fasting blood glucose levels and whether it can potential push glucose-intolerant patients into frank [type 2 diabetes]. Further study is required to establish the clinical significance of these interactions and to indicate whether physicians should consider alternatives to combination treatment involving paroxetine and pravastatin in patients with diabetes.”

Notably, the current study findings did not suggest that these potentially deadly interactions could occur between any other statins and selective serotonin reuptake inhibitors.

In general, pharmacists should be proactive when it comes to potential medication interactions.

“It’s a common mistake we make in health care, that we’re extremely reactive. We wait for something to happen, then we respond to it,” Natasha Nicol, PharmD, FASHP, director of global patient safety affairs at Cardinal Health, previously told Pharmacy Times. “We often focus on the harmful event itself, and not what led up to it.”