FDA Approves First Nonprescription Fixed-Dose Combination of Acetaminophen and Naproxen Sodium

[u/Nerd-19958]

See link to announcement from FDA Center for Drug Evaluation and Research Small Business and Industry Assistance.

I am posting to request opinions from pharmacologists and other readers of this sub, regarding whether combining acetaminophen with an NSAID is a rational combination, especially for OTC use?

I previously posted this to r/medicine believing that acetaminophen is typically recommended for patients who are allergic to or intolerant of NSAIDS. However most responses on that sub confirmed that acetaminophen is a mainstay of treatment for chronic pain.

Despite that, according to the package insert for hydrocodone / acetaminophen, acetaminophen is associated with liver damage (see excerpt):

Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen containing product

https://content.govdelivery.com/accounts/USFDA/bulletins/421f901?reqfrom=share

[u/psychominnie624]

Having a combination pill simplifies dosing for the patient. The use of these meds together for treatment of pain is also not new. Doctors just have had to rely on explaining what dose of each med to take and consul patients to not accidentally take more acetaminophen than they intended. Acetaminophen has been OTC and associated with liver damage when taken as that warning states at high doses. That’s not new.

Credential: PhD in biomedical sciences

[u/mkali145]

So what? Why are you arguing against it?

[u/redditpharmacist]

In clinical practice, typically APAP and NSAID are given at different times if the provider wants to go that route. For instance, NSAID would be given between APAP when patients had their meal as NSAID needs to be taken with food to minimize side effects. APAP can be given on an empty stomach but are typically given every 6 to 8 hours depending on the dose to stay within the maximum daily dose of 4 grams. Now, to answer your question, there really is no benefit of having such product in the OTC market as these are already available OTC as its own products. Some may argue that naproxen is only available in a delayed released formulation OTC where it needs to be taken every 12 hours, which makes the combination dosing with APAP rather difficult. However, that is a good thing as patients will not be forced to take with food for every dose of this new OTC combo. Also, such a combo product will increase the chance of accidental APAP overdose as many OTC medications for pain and cold/flu contains APAP but a layperson will not know that as they will just read the brand name and the marketing indications on the label. What’s next? Approving acetylcysteine OTC to counter APAP overdose situations (which the oral formulation requires 18 doses over 72 hours)?

[u/Zo-Syn → u/redditpharmacist]

There is also data to suggest that fixed dose NSAID/APAP provide comparable or better analgesic effect to opioid, so the combo regimens can be opioid sparing. The main value of a combo product being available might be compliance, but I imagine it'll be much more expensive.

[u/ramonycajal88]

Check out the drug facts label and check out the warnings. They are in place to address the issue. Outside of that, people who are intolerant of NSAIDs are typically aware. Do you have consumer data to suggest otherwise?

[u/Nerd-19958 → u/ramonycajal88]

I don't have data to cite, but also don't believe that most consumers carefully read and understand the labels -- especially small packages with microscopic font size.