Most medications (93%) contain some sort of potential allergen, according to results from a recent study published in Science Translational Medicine. And while this may not be problematic for most people, it may be for some.
“For most patients, it doesn't matter if there's a little bit of lactose, a little bit of fructose, or some starch in there. However, there is a subpopulation of patients, currently of unknown size, that will be extremely sensitive to those and develop symptoms triggered by the inactive ingredients,” said co-lead author Daniel Reker, Swiss National Science Foundation postdoctoral student, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA.
All medications include inactive ingredients, for various reasons. These can include enhanced stability or absorbability, or even for texture or color. But, according to a recent review, the oral solid formulations of the most frequently prescribed medications in the United States are comprised of 75% inactive ingredients. Among these, atorvastatin, for example, has an inactive ingredient mass of 770 mg. And while simvastatin had the lowest inactive ingredient content (50 mg), these ingredients accounted for a full 90% of its total mass.
“Right now, there is an imbalance in the amount of information and understanding out there with respect to the inactive components of medication,” said senior author Giovanni Traverso, MB, BChir, PhD, assistant professor, Department of Mechanical Engineering, MIT, and gastroenterologist, Brigham and Women's Hospital, Boston, MA. “I think there's a tremendous underappreciation of the potential impact that inactive ingredients may have.”
Dr. Traverso and colleagues searched medical journals for accounts of allergic reactions to inactive ingredients. They found that these studies failed to include patients with an intolerance to a specific ingredient, which means that the incidence of reactions may be even larger.
Then, to discover what inactive ingredients may be in prescription and nonprescription medications, they searched the National Library of Medicine’s database, Pillbox.
Reker, Dr. Traverso, and colleagues found the following:
- In most cases, over 50% of each pill was comprised of inactive ingredients, and—in some—over 99%.
- The average tablet/capsule contained 8.8 inactive ingredients.
- A full 93% of medications contain allergens, including lactose, dyes, and even peanut oil. Almost all had ingredients that may be intolerable to some, such as gluten.
- Over 50% of medications contain FODMAP sugars, which are known to trigger digestive problems in those with irritable bowel syndrome.
- Packaging contained no warning for these ingredients, other than peanut oil.
The top three inactive ingredients that may act as allergens or could be contaminated with allergens included lactose (found in 44.82% of solid oral dosage forms of medication), corn starch (found in 36.54%), and the polymer polyethylene glycol (found in 36.03%).
For example, they found that lactose was commonly included in a full 45% of all oral solid dosage forms, with lactose content of nearly 600 mg per pill. When considering that 75% of the world’s population is lactose intolerant, this finding has serious ramifications—especially for those taking multiple concurrent medications for multiple comorbidities, such as hypertension and hypercholesterolemia.
The same is true for gluten. In this study, 18% of manufacturers stated that their medications contain gluten. But of the 69% who claim they provide gluten-free products, only 17% could actually provide documentation to prove this. For individuals with celiac disease, who can suffer severe reactions from doses of gluten as low as 1.5 mg/d of chronic exposure, again, the ramifications are serious.
The authors are hopeful that their findings will raise awareness of the risks of inactive ingredients for some patients, and perhaps lead to more information about inactive ingredients required from pharmaceutical companies, alternative formulations for those with allergies or sensitivities, and more patient awareness.
Dr. Traverso, Reker, and colleagues are currently conducting a follow-up to their study, where they are polling healthcare providers to learn how widespread this problem is.
“There need to be more clinical trials and more data out there so that we can really dive deep into how many patients are affected and how we can help them,” Reker concluded.
Ultimately, they called for a greater awareness of the inclusion and impact of the inactive ingredients in medications.
“Recognizing that the inactive portion of a medication, which corresponds on average to two-thirds of the administered material, may be more ‘active’ than previously anticipated, we foresee potential implications for medical protocols, regulatory sciences, and pharmaceutical development of oral medications,” the authors concluded.
Watch for medications that contain albumin (produced from eggs), lactose, starches, sucrose or sugar, sulphites, tartrazine, and vegetable oils. In patients with allergies or sensitivities to any of these ingredients, consider prescribing other options.
This study was funded by the Swiss National Science Foundation, the Brigham & Women’s Department of Medicine Residency Program and Division of Gastroenterology, the Alexander von Humboldt Foundation Feodor Lynen Fellowship, the National Institutes of Health, and the MIT-IBM Watson AI Lab.