Understanding When did the FDA approve acetaminophen?

October 12, 2025 •

3 min read

The US Food and Drug Administration (FDA) initially approved the drug acetaminophen in 1951, a crucial moment that marked the beginning of its widespread use as an analgesic and antipyretic. This initial approval laid the groundwork for the development of popular brands like Tylenol, which would later become available to the public over-the-counter.

Quick Summary

The active ingredient acetaminophen was initially approved by the FDA in 1951 for prescription use. Brand-name versions, like Children's Tylenol Elixir, received approval later, with over-the-counter access granted in 1960. Subsequent regulations have addressed safety concerns and potential overdose risks over the decades.

Key Points

Initial FDA Approval: The drug acetaminophen was first approved by the FDA in 1951 for prescription use, based on research showing it was a safer alternative to older analgesics.
Tylenol's Launch: McNeil Laboratories introduced the brand Tylenol in 1955, starting with a children's elixir available only by prescription.
Over-the-Counter Release: Tylenol was approved for non-prescription, over-the-counter (OTC) sale in 1960, making it widely accessible to the public.
Safety Profile: Compared to aspirin, acetaminophen was marketed as having less risk of gastrointestinal irritation and was safer for pediatric use, which contributed significantly to its popularity.
Ongoing Regulation: The FDA has continued to update regulations for acetaminophen over time, adding warnings about potential liver damage in 1998 and 2009, and limiting prescription doses in 2011.
Recent Labeling Changes: In 2025, the FDA initiated a label change process to include warnings about a possible association between prenatal exposure and neurodevelopmental disorders, though it remains the recommended OTC choice during pregnancy.

Acetaminophen's Emergence in Medicine

Acetaminophen, also known as paracetamol outside the United States, has a history that predates its formal FDA approval by decades. The compound was first synthesized in 1878, but it wasn't immediately recognized for its therapeutic potential. In the late 19th century, drugs like acetanilide and phenacetin were used for pain and fever, but they were later found to have serious side effects, including methemoglobinemia and renal toxicity. Researchers eventually identified acetaminophen as a safer alternative and a major metabolite of phenacetin, paving the way for its clinical development.

The Path to Initial FDA Approval in 1951

The formal journey to FDA approval began in the early 1950s after studies at Yale and New York University highlighted acetaminophen's efficacy and safety compared to its predecessors and to aspirin. This new research was presented to the medical community in 1951, the same year the active pharmaceutical ingredient received its initial approval from the U.S. Food and Drug Administration. This approval enabled the drug's use in prescription formulations, including an early intravenous version.

Introduction of the Tylenol Brand and OTC Status

While the drug was approved in 1951, its widespread availability came later through branded products. McNeil Laboratories introduced its own formulation, Children's Tylenol Elixir, as a prescription-only product in 1955. It was marketed to physicians and pediatricians as a safer alternative to aspirin, which had known risks of gastrointestinal irritation and Reye's syndrome in children. The brand name Tylenol was cleverly derived from the drug's chemical name, N-aceTYL-p-aminophENOL. Following its success, Tylenol gained approval for over-the-counter (OTC) sales, becoming available to the public without a prescription in 1960.

Evolution of FDA Regulations and Safety Warnings

Over the decades, the FDA has continued to monitor and regulate acetaminophen, addressing evolving safety concerns. While largely safe and effective when used as directed, overdose can lead to severe liver damage.

Key FDA regulatory milestones for acetaminophen include:

1998: The FDA made liver damage warnings for combination products containing acetaminophen and alcohol mandatory on all product labels.
2009: The agency began requiring additional warnings on product labels about the risks of severe liver damage if not taken as directed.
2011: The FDA requested that manufacturers of prescription combination products limit the maximum amount of acetaminophen to 325 mg per tablet or capsule.
2013: The FDA began requiring a warning on OTC product labels regarding severe skin reactions.
2025: The FDA announced it is initiating a process for a label change to reflect evidence suggesting a possible association between prenatal use and increased risk of neurodevelopmental disorders like autism and ADHD. However, the agency also stated that a causal link is not established, and it remains the safest OTC option during pregnancy.

Comparison: Acetaminophen vs. Aspirin


Feature	Acetaminophen (Tylenol)	Aspirin	Notes
Mechanism	Inhibits prostaglandin synthesis centrally; analgesic and antipyretic.	Inhibits cyclooxygenase enzymes (COX-1 & COX-2) both centrally and peripherally; analgesic, antipyretic, anti-inflammatory, and antiplatelet effects.	Acetaminophen lacks significant anti-inflammatory effects.
Stomach Irritation	Generally well-tolerated and less likely to cause stomach irritation.	Known to cause gastrointestinal side effects and irritation.	A key advantage for acetaminophen, especially for those with ulcers or sensitive stomachs.
Use in Children	Safe for use in children when dosed correctly.	Linked to Reye's syndrome in children with viral infections, making it unsafe for pediatric fever.	This safety profile in children drove early marketing and adoption of Tylenol.
Liver Toxicity	High doses can cause severe liver damage; overdose is a leading cause of acute liver failure.	Overdose can lead to various toxic effects, including salicylism, but liver failure risk differs from acetaminophen.	Crucial to stay within recommended daily limits for acetaminophen.

The enduring legacy of acetaminophen

Since its initial FDA approval in 1951, acetaminophen has become a cornerstone of both prescription and over-the-counter medicine for pain relief and fever reduction. Its journey from a less toxic alternative to older drugs to a household name is a testament to its effectiveness and perceived safety profile, particularly for use in children. As with many long-standing medications, continuous FDA oversight has led to revised labeling and dosage guidelines to ensure public safety as our understanding of its risks evolves, especially concerning the potential for liver toxicity and, more recently, prenatal exposure.

For more detailed information on FDA regulations and the history of drug regulation in the U.S., consult the FDA's official resources. Its availability and effectiveness ensure its continued place as a vital component of modern healthcare, provided it is used responsibly and with careful attention to dosage instructions.

Frequently Asked Questions

The drug acetaminophen, as an active ingredient, received its initial approval from the U.S. Food and Drug Administration (FDA) in 1951.

McNeil Laboratories introduced the brand Tylenol in 1955 as a prescription-only children's elixir.

The brand Tylenol was approved for over-the-counter (OTC) sales in 1960, five years after its initial introduction.

A key difference is that acetaminophen has no significant anti-inflammatory properties, unlike aspirin. It is also less likely to cause gastrointestinal irritation and is safe for use in children.

Yes, in 2025, the FDA initiated a process to add a warning label about a potential association between prenatal use and neurodevelopmental disorders like autism and ADHD, though they also stated it remains the safest OTC option for pregnant women.

The primary risk of taking too much acetaminophen is severe liver damage, which can be life-threatening and is a leading cause of acute liver failure.

Overdoses can happen because acetaminophen is included in over 600 products, including cold, flu, and allergy medications. It is important to check all medication labels to avoid taking multiple products containing the same ingredient.

Yes, generic acetaminophen contains the same active ingredient and is considered therapeutically equivalent to brand-name versions. The manufacturer does not have a patent on the drug itself.