If you’ve looked at the ingredient list for a medication, you’ve probably seen that there are active ingredients - the part that has a biological function - and inactive ingredients - all the other stuff that forms the pill we ingest. Those inactive ingredients might aid in absorption or improve the shelf life, or just give the medication color or a better taste. Researchers have taken a close look at those so-called inactive ingredients and found that some of the most commonly prescribed medications in the US carry at least one ingredient that can cause a harmful side effect. At least 90 percent of oral medications contain something that can trigger gastrointestinal distress or allergic reactions, like gluten, dyes, lactose or peanut oil. The work has been reported in Science Translational Medicine.
“When you're a clinician, the last thing you want to do is prescribe a medication that could cause an adverse reaction or allergic reaction in a patient,” said the corresponding author of the study C. Giovanni Traverso, MB, BChir, Ph.D., a gastroenterologist in the Division of Gastroenterology at the Brigham and in the Department of Mechanical Engineering at MIT. “This project was inspired by a real-life incident where a patient with Celiac disease was prescribed a medication and the formulation of the pill they picked up from the pharmacy had gluten in it. We wanted to understand the problem and drill down to characterize the entire universe of inactive ingredients across thousands of drugs.”
In this study, the researchers assessed around 354,597 inactive ingredients, which are not supposed to have a direct effect, in 42,052 oral medicines. Previous work involving huge groups of people has indicated that these ingredients are biologically inactive, but there have been case reports, such as the one above, suggesting that these ingredients negatively impact some individuals with allergies or intolerances.
“What is really striking about this data set is its complexity,” said biochemical data scientist and the first author of the study Daniel Reker, Ph.D. “There are hundreds of different versions of pills or capsules that deliver the same medication using a different combination of inactive ingredients. This highlights how convoluted the possible choices of inactive ingredients are, but also suggests that there is a largely untapped opportunity today to specifically select the most appropriate version of a medication for a patient with unusual sensitivities.”
A literature search revealed that 38 inactive ingredients are thought to cause allergic symptoms in some people after they’ve been orally ingested. At least one of those 38 ingredients can be found in 92.8 percent of the medications the researchers assessed. Specifically, lactose can be found in 45 percent of drugs, food dye in 38 percent, and peanut oil in only 0.08 percent, but for a medication like progesterone, few versions don’t contain that inactive ingredient.
"While we call these ingredients inactive, in many cases, they are not. While the doses may be low, we don't know what the threshold is for individuals to react in the majority of instances," said Traverso. "This pushes us to think about precision care and about the role for regulation and legislation when it comes to labeling medications that contain an ingredient that may cause an adverse reaction."