The ‘inactive ingredients’ in your medicines may actually be active

Recall when you popped a paracetamol for a headache? If you bothered to read the packaging, you would find it contained 500mg of paracetamol as “active ingredient”. Then there’s the “inactive ingredient”-they don’t do anything for your headache, but they are put in to make the drug taste better, or stay longer, or a number […]

Recall when you popped a paracetamol for a headache? If you bothered to read the packaging, you would find it contained 500mg of paracetamol as “active ingredient”. Then there’s the “inactive ingredient”-they don’t do anything for your headache, but they are put in to make the drug taste better, or stay longer, or a number of other reasons.

Inactive ingredients have been a part of medications for ages. Even herbalists might throw in a dash of spice to make that bitter-tasting herbal drink easier to swallow.

Now new research suggests inactive ingredients may also cause adverse reactions.

A team of investigators from Brigham and Women’s Hospital and Massachusetts Institute of Technology has found more than 90% of all oral medications tested contained at least one ingredient that can cause allergic or gastrointestinal symptoms in sensitive individuals.

The study was done in the US and the findings published in the journal 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 corresponding author Dr Giovanni Traverso, 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.”

Traverso collaborated with biochemical data scientist Daniel Reker, PhD, internal medicine resident Steven Blum, MD, the Brigham’s executive director of Pharmacy John Fanikos, MBA, RPH, and others to analyze data on the inactive ingredients found in 42,052 oral medications that contained more than 354,597 inactive ingredients.

Inactive ingredients do not contribute to the therapeutic effects of drugs. They are tested for safety using population studies but case reports have suggested they may cause adverse reactions in people with allergies or are unable to tolerate certain substances.

“What is really striking about this data set is its complexity,” said Reker.

“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.”

The team found a total of 38 inactive ingredients that have been described in the literature to cause allergic symptoms after oral exposure. The authors report that 92.8 percent of the medications they analyzed contained at least one of these inactive ingredients.

Specifically, 45 in 100 medications contained lactose, and another 33 in 100 contained a food dye.

It is unclear what amount of an ingredient is necessary to trigger a reaction in sensitive individuals — the content of lactose in a medication, for instance, may be too low to cause a reaction in many patients, except for those with severe lactose intolerance or those taking many medications containing lactose.

“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 labelling medications that contain an ingredient that may cause an adverse reaction.”