Hidden compounds in many medications can trigger allergies

An analysis of 42,000 pill recipes shows 93 percent have potentially problematic ingredients


TOUGH PILL TO SWALLOW  The inactive ingredients in many pills and capsules may trigger allergic reactions or intolerances in some patients.


For some patients, the so-called inactive ingredients in pills may be more active than previously thought.

Every pill contains a pharmaceutical drug with some therapeutic effect on the body, as well as a mixture of inactive compounds added to boost the medication’s effectiveness or simply to make the pill more palatable. Inactive ingredients are generally considered harmless. But many pills contain chemicals that can cause allergic reactions or digestive problems in some patients, according to an analysis of the chemical ingredient lists for thousands of pills.

Researchers searched a database that contained about 42,000 recipes for oral medications marketed in the United States. Of those, 92.8 percent contained at least one of 38 inactive ingredients that have triggered allergic reactions in patients, the researchers report online March 13 in Science Translational Medicine. And 55 percent of pills contained at least one of a class of sugars called FODMAPs, which can cause digestive problems in people with irritable bowel syndrome.  

Science News spoke with study coauthor Giovanni Traverso, a gastroenterologist and biomedical engineer at Brigham and Women’s Hospital in Boston and MIT, about what we do and don’t know about the risks posed by oft-overlooked inactive ingredients. His comments are edited for clarity and brevity.

Why are potential allergens and irritants so common in pills?

Once an inactive ingredient passes toxicity screening conducted by the U.S. Food and Drug Administration, it’s considered safe for the general population in approved levels. But as more people take medications that contain these chemicals, “we start to appreciate and uncover some of the potential side effects” for a minority of patients that weren’t revealed during the approval process, Traverso says.

Do healthcare providers consider inactive ingredients when prescribing medication?

In Traverso’s experience, no. “If I’m prescribing something for someone who’s experiencing reflux, I will type, ‘Omeprazole, 20 milligrams once or twice a day.’ I don’t prescribe, ‘Omeprazole, the version that doesn’t have this and doesn’t have that.’” There may be dozens of pills on the market that contain the same active ingredient, each with its own cocktail of inactive add-ons. “The healthcare provider doesn’t really know which formulation the patient is going to receive, because that’s generally governed by the pharmacy.”

Drug manufacturers are required to put warning labels on pills made with some chemicals, like peanut oil. But many allergens and other sources of intolerance fly under the radar, Traverso says. “A pharmacist isn’t likely asking the patient, ‘Do you have irritable bowel syndrome? Are you lactose intolerant?’” So neither the doctor nor the pharmacist may know if a patient is liable to suffer side effects from inactive ingredients in their medication.

How many people could react poorly to inactive ingredients?

We just don’t know, Traverso says. Pharmaceutical companies rarely disclose how much of each chemical is contained in their pills; the database that Traverso’s team examined specifies only whether a pill contains an ingredient or not.

Even if manufacturers did disclose all the levels of inactive ingredients in their products, it’s not entirely clear how many patients would experience negative side effects. “For some of these ingredients, we have a sense of how much is sufficient to elicit an intolerance or an allergy,” Traverso says. Gluten is one example. “But for some of these other sugars, we have less of a sense. Part of the future work is really trying to dive into this, and understand how much for an individual is too much … I suspect that there’s a lot of variation across the population.” Risk assessment is especially tricky for patients who take several different types of pills per day.

What could be done differently?

If healthcare providers had better access to all the information of what goes into different pills, doctors could better judge the patients’ risks of potential side effects, Traverso says. Doctors who assess a patient’s tolerance for inactive ingredients as a routine part of the prescription process, rather than focusing solely on active ingredients, could offer a more personalized treatment approach with fewer potential complications, he says. “Understanding who’s sitting in front of you, and matching that person to the optimal set of drug formulations that are going to help them is likely to benefit the patient.”

Previously the staff writer for physical sciences at Science News, Maria Temming is the assistant managing editor at Science News Explores. She has bachelor's degrees in physics and English, and a master's in science writing.

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