Inactive Ingredients in 90 Percent of Drugs Can Have Unintended Consequences

"It is not something that most prescribers would immediately think about." 

People with allergies or food sensitivities are already used to keeping on top of every ingredient in the meals they eat. But not everyone may think to look for these triggering substances on the back of their typical prescription drug bottle.

In a paper published Wednesday in Science Translational Medicine, researchers at Brigham and Women’s Hospital and MIT report that 92.8 percent of oral prescription medications contain at least one inactive ingredient like lactose or chemical dyes that might cause allergic, or at least uncomfortable, reactions in some people. Study co-author Daniel Reker, Ph.D., a postdoctoral researcher at MIT, points out that the concentrations of these ingredients are so small that most people don’t have to worry. But for especially sensitive individuals, even the tiny amounts of an allergen found in a pill can be risky.

“We were shocked to see how omnipresent these critical inactive ingredients are in medications” he tells Inverse. “While the quantities of included ingredients might be too small to be relevant for a majority of the population, very sensitive patients might be heavily affected by such effects.”

What Inactive Ingredients Are Present in Medications?

Working with a team at Harvard Medical school consisting of Giovanni C. Traverso, Ph.D., and Steven Blum, Reker combed through data on the formulations of 42,052 different prescription medicines. They looked for the kinds of inactive ingredients that help the pills keep their shape, change taste, or alter color, but don’t confer any biological effects. Importantly, these substances are all legal, it’s just that some people react poorly to them.

Pills.
Reker and Traverso found that 92.8 percent of medications in their study contained one ingredient that might cause an allergic or adverse reaction in some patients. 

For instance, they report that 45 percent of these medications contained lactose — which can cause both allergic reactions and intolerances, though it’s unclear exactly how much lactose you need to ingest to trigger a reaction. They also note that 33 percent of medications contained chemical dyes that have been associated with adverse reactions.

But Reker points out that the bigger issue is that these medications also contain ingredients that can make patients with certain conditions even more uncomfortable than they already are. The team notes, for example, that 55 percent of the medications contained at least one sugar (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) which are known to increase discomfort in patients with irritable bowl syndrome.

“Patients suffering from irritable bowel syndrome might be sensitive to the inclusion of certain types of sugars in their medication,” he explains. “Patients with asthmatic conditions might react to specific colorants such as tartrazine. We are currently conducting a questionnaire among healthcare professionals to quantify how many prescribers are aware of such effects, but in our personal experience it is not something that most prescribers would immediately think about.”

Why It’s Worth Looking Into Alternative Pill Recipes

While these small amounts of allergens might not be a huge concern for most people, Reker notes that trace amounts of a substance can make a medication unusable for some patients. The problem is that when you need a certain medication for an illness, you’re caught between two conditions: the allergy, and your need for that drug.

For example, Reker and Traverso note that less than 1 percent of the medications in the study contained peanut oil. Out of that small number, though, 100 percent of progesterone formulations in their data contained peanut oil, as did 62.5 percent of valproic acid capsules (a drug used to treat epilepsy). When peanut oil is in the pills, FDA regulations require it to be marked on the bottle, but in some cases, this leaves few — or no —safe options for extremely sensitive individuals.

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Inactive ingredients in prescriptions medications usually control shape, color, or flavor and might cause some adverse events in certain patients. 

Fortunately, in the case of valproic acid, there’s a simple fix. Some companies will substitute peanut oil with corn oil, which turns drugs into viable alternatives for people with peanut allergies. Reker hopes this is an example other pills that contain lactose, for instance, may be able to replicate.

“There are many examples where alternative formulations without these critical ingredients are available today or are likely to be possible through formulation design,” he says.

The researchers hope that one day we will find new solutions that take these drug ingredients out of the process completely. They believe that, although these adverse events might only happen in a few people, drug companies and physicians owe it to their patients to invest in drug formulations that are accessible to every person.

“This really brought it home for us that we might have so far not put our best foot forward in terms of clinical, regulatory, and clinical workflows to ensure that we are providing the best treatment to all patients,” Reker says.