Not so Inactive: Excipients in Medications

Not so Inactive: Excipients in Medications May Trigger Adverse Reactions in Some Patients – MPR – Cassandra Pardini, PharmD – Apr 2019

Despite all the strange reactions I and others have had when our pharmacy gives us a different manufacturer’s version of a familiar medicine, many medical professionals still claim that different “versions” of medication are “exactly the same”. By now, there’s evidence that this simply isn’t true.

I’ve previously posted about how generics are often not “the same” as brand name drugs, but there can also be differences between different manufacturers’ versions of the same generic drug.

For sensitive people, these differences can be critical.

An oral drug product contains both

  1. the active pharmaceutical ingredient (API) as well as
  2. a mixture of inactive ingredients, or excipients.

Inactive ingredients are used to alter the physical properties of a medication, while the API is intended to produce the desired pharmaceutical effect of the agent.

Excipients may be added to a medication to

  • improve absorption,
  • alter taste,
  • increase stability, or
  • render the medication tamper resistant.

Although there are thousands of known inactive ingredients that have been tested and have established safety at the population level, numerous case reports have been published suggesting some excipients may cause adverse reactions in some patients.

when analyzing the most frequently prescribed oral agents, it was found that the inactive ingredient portion of the medication typically accounted for 75 ± 26% of the total mass of the product.

This describes a surprisingly wide range from less than half (75 – 26 = 49%) to over 100% (75 + 26 = 101%).

This kind of variance is already a problem because it allows for so much variety in the generic versions.

information regarding the mass content of individual inactive ingredients contained in an agent is not typically accessible to patients or healthcare providers.

This is outrageous when normally, all food for human consumption must be labeled with every single ingredient, no matter how tiny a fraction is in the food.

When we are already not in the best of health (that’s why we’re taking the medication in the first place) such secrecy could be deadly. Medications should be required to list at least as much information as food.

In their review, the study authors also highlighted the complexity of the formulation landscape due to

  • the number of inactive ingredients contained in one oral drug product as well as
  • the diversity of available formulations of the same API

the investigators determined that the average oral drug product contains 8.8 excipients.

Although inactive ingredients enhance a drug product’s physical properties and have been deemed safe, clinical reports documenting adverse reactions caused by excipients have been increasing.

the team of investigators found that >90% of all oral medications contain at least one adverse reaction-associated inactive ingredient (ARAII) that can trigger an allergy or intolerance in sensitive patients

the study authors found that 38 inactive ingredients have been described as a trigger of allergic symptoms following oral exposure

Additionally, the study revealed that 92.8% of all oral agents possess at least 1 potential allergen.

only 28% of active ingredients have at least 1 available formulation that avoids all of these potential allergens, and only 12% of APIs are free of inactive ingredients that have been reported to cause allergic reactions.

the selection of a medication should include a review of the formulation in addition to the API in order to prevent any adverse reactions.

The study authors concluded,

“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.”

References (for those that want more information)
Reker D, Blum SM, Steiger C, et al. Inactive ingredients in oral medications. Sci. Transl. Med. 13 March 2019; 483. DOI: 10.1126/scitranslmed.aau6753.
Inactive ingredients in pills and capsules may cause allergic, adverse reactions [news release]. Eurekalert! Web site. March 13, 2019. Accessed March 20, 2019.

1 thought on “Not so Inactive: Excipients in Medications

  1. canarensis

    It’s also infuriating that, if they’re telling the truth, the manufacturers of drugs (even those in the States) don’t even know what the “inactive” ingredients are: I had some problems at one point & called the US makers of 2 or 3 of the meds I was on, trying to find out what the inactives were. They all insisted that there was no way to know, that they got the cheapest available out of a broad list of things that would work, & they had no way to know what they got b/c they got the inactive stuff from other countries & the suppliers just got batches of varying ingredients & didn’t know what was in ’em. Marvy.
    What a way to run a railroad.

    Liked by 1 person


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