Overlooked Ingredients In Medicines Can Sometimes Trigger Side Effects

If you have a bad reaction to a medicine, it might not be the drug itself, but what are called "inactive ingredients" in the pill or capsule.

An article published Wednesday in Science Translational Medicine surveys this field and finds ingredients that are potentially troublesome for some people are ubiquitous.

For example, a few years ago study co-author Giovanni Traverso, a gastroenterologist at Harvard-affiliated Brigham and Women's Hospital, came across a patient with a severe gluten intolerance called celiac disease. The person was having trouble with a medication that apparently contained gluten as an inactive ingredient — potentially making the condition worse, not better.

Traverso, who is also a biomedical engineer with an appointment at MIT, started exploring this topic with some colleagues by weighing pills in the hospital pharmacy. They concluded that, on average, about 75 percent of a pill or capsule is made up of inactive ingredients – that is, material other than the chemical or chemicals that determine the therapeutic effect of a drug.

In their article, the scientists say drug companies have more than a thousand of these inactive constituents to choose from. "In some instances there can be up to 35 of them in a single pill," Traverso says in an interview.

Traverso says these inactive ingredients are essential to stabilize medications and sometimes to help the body absorb the active ingredients. "I don't want to malign inactive ingredients in any way," he says. "I think inactive ingredients are very helpful."

But they can include materials such as gluten and lactose, and dyes that can trigger allergies.

In general, the amounts in a given pill aren't concerning. But many people take multiple medicines, and if those drugs contain the same inactive ingredients, the doses can add up.

If you are lactose intolerant and take a pill that uses lactose as an inactive ingredient, "it's probably not going to manifest in any significant symptoms," he says. "But as the number of pills you're taking [increases], then certainly you might cross that threshold."

One challenge in understanding the scope of this problem is, it's often not clear how much of a particular substance is necessary to trigger an allergy or other reaction.

"It's something that might vary from one person to another," Traverso says. But for a lot of these ingredients, "we don't really know today."

The Food and Drug Administration regulates these drug ingredients. Among other actions, it has issued draft guidelines that would specify how companies should label drugs that contain gluten.

Dr. John Kelso, an allergist at the Scripps Clinic in San Diego, has reviewed the issue of allergens in medications. He says reactions are actually quite uncommon. In fact, it's usually a false alarm.

For example, after many years worrying about the traces of egg protein in flu vaccines, health officials now say that people with egg allergies are not at risk from the shot.

Overreaction to this worry can actually backfire. "Oftentimes the medications are being withheld from patients who say they're allergic to eggs or soy or something else that may be in the medication," Kelso says, "but it is actually not a problem."

Penicillin, though an active ingredient, is a prime example of overreaction.

"We realized lately that approximately 95 percent of patients who are labeled penicillin-allergic are not," he says, "either because they never were or because they had an allergy that waned with the passage of time." An allergist can test people to see if they're actually allergic to this useful and inexpensive antibiotic.

For people who are concerned about the inactive ingredients, Traverso says it is possible to track down that information. Look through the fine print in the instructions (referred to as a package insert) that come with your medication, "and eventually you will find it," he says.

The National Library of Medicine also has an online database, called Pillbox, with this information.

Different manufacturers of the same medicine often use different inactive ingredients, so if one drug might be causing trouble, it's worth considering a switch to the same product produced by a different manufacturer, Traverso says.

He and his colleagues have a patent pending on an algorithm that is designed to make this sleuthing easier. They're thinking about developing a consumer app or some software to help doctors and pharmacists review all the drugs they are taking, so they can alert their patients to potentially troublesome inactive ingredients.

You can reach NPR Science Correspondent Richard Harris at rharris@npr.org.

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