Cambridge, MA—Do so-called inactive ingredients really have no effect on patients who use them?

That question was raised in a study recently published by Science Translational Medicine.

Researchers from Brigham and Women’s Hospital (BWH) and Massachusetts Institute of Technology (MIT) and colleagues determined that 90% of all oral medications, including the most commonly prescribed drugs in the United States, whether prescription or OTC, contain at least one ingredient capable of causing an adverse reaction. The study points out that inactive ingredients are added to improve the taste, shelf life, absorption, and other characteristics of a pill.

Those ingredients include lactose, peanut oil, gluten, and chemical dyes, the study team reports.

“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,” explained corresponding author C. Giovanni Traverso, MB, PhD, a gastroenterologist in the Division of Gastroenterology at BWH 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.”

Researchers analyzed data on the inactive ingredients found in 42,052 oral medications that contained more than 354,597 inactive ingredients. Although inactive ingredients have been tested for safety at the population level, case reports suggest that inactive ingredients have the potential for causing adverse reactions in patients with allergies or intolerances.

“What is really striking about this data set is its complexity,” said coauthor Daniel Reker, PhD, a biochemical data scientist. “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.”

Identified were 38 inactive ingredients that have been pinpointed in the literature as causing allergic symptoms after oral exposure. The authors report that 92.8% of the medications they analyzed contained at least one of these inactive ingredients. Here is what they found:
• Approximately 45% of medications contained lactose
• Approximately 33% of medications contained a food dye
• About 0.08% of medications contained peanut oil; also, for specific drugs such as progesterone, there are few alternatives that do not contain this 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,” Traverso emphasized. “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.”

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