How Tylenol Elixir Became an “Exceptionally Safe” Pain and Fever Reliever for Children (NDA 009927)
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By Dr. Donald Fox
When you pick up a bottle of children’s acetaminophen today, it’s easy to forget that this medicine had to prove itself—slowly, carefully, and in writing—to the U.S. government.
What you shared is a fascinating paper trail: internal FDA correspondence, clinical notes, and the 1972 Federal Register notice that all orbit around NDA 009927—McNeil Laboratories’ 1955 New Drug Application for Tylenol Elixir (N-acetyl-p-aminophenol, later known to everyone as acetaminophen). It shows us how a pediatric liquid pain reliever went from “new drug” to “widely accepted OTC medicine.”
Let’s walk through what’s in there.
1. The 1955 Moment: FDA Says Yes
On June 3, 1955, FDA acknowledged McNeil’s NDA 009927 for “Elixir Tylenol.” The company had sent in its application April 13, 1955, followed up with label revisions through May, and the agency finally wrote back that the application had been “filed on May 13, 1955” and was now effective. That’s FDA-speak for: you met the standards under Section 505; you can market this.
They even asked McNeil to send five copies of the final printed label and three finished market packages—because back then, physical labeling mattered as much as the formulation.
2. What Was the Drug?
The product was very specific:
Name: Tylenol Elixir
Active ingredient: N-acetyl-p-aminophenol (what we now call acetaminophen)
Strength: 120 mg per 5 cc (1 teaspoon)
Route: Oral
Indication: Analgesic (pain) and antipyretic (fever), especially for children
This made it different from aspirin products of the day—less gastric irritation, safer in pediatrics, and not salicylate-based.
3. The Pediatric Study That Carried Weight
One of the most important pieces in that packet is the clinical report by Donald A. Cornely, M.D., and Joseph A. Bler, M.D., Philadelphia—a pediatric series using liquid N-acetyl-p-aminophenol in infants and children with fevers, pain, and common infections.
Key points from that study:
141 total pediatric patients were treated
In the 20 patients who got only Tylenol (no antibiotics), 90% had a good-to-excellent antipyretic response
Analgesic effect was rated good in a majority of mixed-medication patients
Side effects? Almost none. 134 of 141 had no observed adverse effects
A second group of 20 hospitalized children received Tylenol for five weeks (with rest weeks in between) to check chronic toxicity—and labs (Hgb, WBC, clotting) stayed normal
That longish pediatric tolerance study was powerful. It let McNeil and later FDA writers say things like “exceptionally safe for use at any age”—a strong line for the era.
4. Why Tylenol Was Pitched as “Safer”
The documents keep contrasting acetaminophen with acetanilide, phenacetin, and salicylates. By the 1950s, medicine knew that some of those older antipyretics could cause methemoglobinemia, anemia, gastric irritation, or bleeding. The metabolism research (Lester, Greenberg, Brodie, etc.) showed that acetaminophen was actually the main, cleaner metabolite of those older drugs.
So the logic was:
Old drugs → sometimes toxic
Their main metabolite in humans → N-acetyl-p-aminophenol
So let’s just give the metabolite → cleaner, safer drug
And the 1952 Elkhart, Indiana “Symposium on N-Acetyl-p-aminophenol” (which the FDA file keeps citing) helped establish that this wasn’t a mystery chemical—it had been studied for absorption, metabolism, and low toxicity in humans.
5. The 1972 DESI Review: FDA Circles Back
Fast-forward to April 20, 1972. FDA publishes a big Federal Register notice listing OTC analgesic/antipyretic products—Tylenol Elixir (NDA 9-927) is on it.
What did the expert panels say?
Panel on Drugs for Relief of Pain:
Said acetaminophen is an effective analgesic
But… noted there were not always “specific, well-controlled and conclusive clinical studies” for every single condition listed on labels (like sinusitis, cervical adenitis, viral infections).
Translation: Yes, it works for pain and fever, but don’t get too creative on the label.
Panel on Neurological Drugs:
Said: don’t claim it treats vague things like “neuritis, neuralgia, radiculitis” unless you specify the disease. That’s why later labels got tighter.
But—and this is the big part—they did not say acetaminophen was ineffective. On the contrary, they accepted the core: oral acetaminophen is an effective analgesic and antipyretic.
6. Pediatric Advantages They Loved
The McNeil materials and the later summaries list the same selling points over and over:
Easy to administer – pleasant, cherry-flavored liquid
Flexible dosing – you can dose by age/weight
Well tolerated – little to no gastric irritation
No salicylate-type clotting issues – so useful where aspirin was a problem
Usually tolerated by aspirin-sensitive patients
That’s basically the modern children’s Tylenol positioning—already present in the 1955–1966 materials.
7. The Safety Letter of 1965
There’s even an internal-style note (Jan. 25, 1965) that states: Tylenol (acetaminophen) is a hydroxyacetanilide structurally related to phenacetin and acetanilide, but “appears to be the least toxic of the acetanilide group” and had been cleared for OTC in 1955—with labeling limits for young children and duration of use. That tracks with the conservative FDA posture of the time: safe, but keep it short and pediatric-guided.
Why This Matters
This packet shows that Tylenol didn’t become America’s go-to pain and fever medicine by accident. It was:
grounded in metabolism research (what does the body really turn these drugs into?)
supported by real-world pediatric use
labeled carefully
and later re-affirmed in the DESI era
And unlike some of its chemical cousins, it survived the 1960s–1970s safety re-evaluations.
Authored for publication by Dr. Donald Fox (Using historical FDA/NDA and DESI source material you provided.)
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