The vast majority of oral medication contains ingredients that can cause side effects in patients, new research suggests.
The culprits are so-called "inactive" ingredients: hundreds of thousands of different additives that help to come up with medicines, but are not the most important functional part of the medicine.
When a doctor gives you a prescription for a drug, the most important part of the drug is what the API is called: the active pharmaceutical ingredient, the chemical that is meant to make you healthy.
But the API is not the only thing in the drugs that people buy.
Up to 99 percent of a pill or tablet can consist of excipients: so-called inert fillers that help the drug differently in terms of appearance, consistency, color, taste or other physical properties.
Excipients, also called bulk substances, are often listed as & # 39; inactive ingredients & # 39; on medication packaging, but that term is a wrong name.
Unlike the API, excipients are not supposed to have any direct therapeutic effect, which is why they are defined as "inactive," but that does not necessarily mean that they are inactive or inert in other ways.
"Although we call these ingredients & # 39; inactive & # 39; in many cases, they are not & # 39;" says gastroenterologist Giovanni Traverso of MIT and Brigham and Women & # 39; s Hospital.
"Although the doses may be low, we do not know what the threshold is for people to respond in most cases."
Traverso was inspired to study inactive ingredients after being involved five years ago in a case in which a celiac patient reacted poorly to omeprazole, a medicine used to treat stomach ulcers.
The formulation taken by the patient contained ingredients derived from wheat products, including gluten. Those components could be the reason why the patient felt nauseous after taking the drug.
"That really brought me home, as far as we know about tablets and the possible adverse effects they may have," says Traverso.
In the new study, Traverso and fellow researchers analyzed the public database Pillbox, which contains information on more than 42,000 oral drugs marketed in the US, and more than 350,000 inactive ingredients used to make the drugs.
On average, tablets or capsules contain 8.8 inactive ingredients, but hundreds have 20 or more, the researchers say, and sometimes more than 30.
Approximately one third of the inactive ingredients only appear once in the database, while other are common components (such as magnesium stearate, which is found in 72 percent of the oral drugs).
Usually inactive ingredients account for more than 50 percent of a pill, but sometimes it is as much as 99 percent, the team says.
None of these statistics is necessarily problematic, but some of the data the team has found is more worrying.
Specifically, 38 of the inactive ingredients identified by the team have been reported to cause allergic symptoms in the past, and 92.8 percent of all oral medication in Pillbox contain at least one potential allergen, while 55 percent have at least one FODMAP sugar contains.
"For most patients, it doesn't matter if it contains a bit of lactose, a bit of fructose or some starch," explains one of the team members, biochemical data scientist Daniel Reker from MIT.
"However, there is a subpopulation of patients, currently of unknown size, who are extremely sensitive to this and develop symptoms caused by the inactive ingredients."
The problem is exacerbated by the fact that while inactive ingredients are usually mentioned on the package, their relative amount in the drug is not detailed.
Also, when doctors prescribe drugs to patients, they can only specify the dosage of API, not the formulation itself – and sometimes it is impossible to avoid certain inactive ingredients in multiple different formulations of a particular drug.
The risks can also be multiplied in terms of older patients, since older people often use different medications – potentially exposing them to a harmful accumulation of inactive ingredients that they may be sensitive to.
"A patient taking 10 prescription drugs would receive an average of 2.8 grams of non-active ingredients daily," the authors write.
"This is a significant amount of excipient material that is administered to patients every day and deserves further consideration."
In short, there are many reasons why the team says more attention should be paid in the future to these ingredients that have flown under the radar so far – as well as how they are regulated and given to patients.
"Accounting for effects of excipients makes advanced formulations possible for drugs that are difficult to obtain and can lead to personalized medicine for vulnerable subpopulations," the authors explain in their paper.
"Such an analysis will enable physicians to create conscious formulas that focus on the well-being of their patients."
It is worth pointing out that three of the authors are mentioned as co-inventors on a provisional patent application for a system that uses algorithms to quantify and describe inactive ingredients in drugs in detail.
On the one hand, this means that they may have a commercial interest in disclosing the risks of inactive ingredients, something that should be kept in mind.
But hopefully this also means that the problems they have identified are easier to navigate thanks to an app or website that can explain exactly what we are buying at the pharmacy.
"We were surprised by the results," Traverso told NBC News.
"It's about almost every pill and capsule, and it's something we don't usually think about."
The findings are reported in Science Translational medicine.