There’s a familiar bottle sitting in countless American medicine cabinets.

It claims to soothe aches, help you fall asleep, and take the edge off long, restless nights.

 

Its name is Tylenol PM. But according to one healthcare professional, those little blue pills deserve a second thought—especially when they’re used night after night.

Dr. Ethan Melillo, a pharmacist based in Rhode Island, doesn’t hold back. He’s openly said that Tylenol PM is one of the medications he strongly dislikes—an unusually blunt stance in medicine. His concern isn’t that the drug doesn’t work. It’s that people often misunderstand it, assuming it’s harmless simply because it’s familiar and sold over the counter.

Tylenol PM: A Risky Two-Ingredient Mix

Tylenol PM isn’t a single medication. It’s a combination of two drugs working together:

Acetaminophen, which reduces pain and fever

Diphenhydramine, an antihistamine that causes drowsiness

On the surface, it sounds convenient—relief from pain and help with sleep in one dose. But Dr. Melillo cautions that this convenience may hide real risks, particularly with frequent or long-term use.

Acetaminophen: Quietly Hard on the Liver

Acetaminophen—the same ingredient found in regular Tylenol—is one of the most widely used pain relievers in the U.S. It’s inexpensive, easy to find, and easier on the stomach than drugs like ibuprofen. However, it places a heavy burden on the liver.

When you take acetaminophen, your liver processes it. During that process, a small amount of a toxic byproduct called NAPQI is produced. Under normal circumstances, your body neutralizes this toxin using an antioxidant called glutathione, preventing harm.

The problem arises when that system is pushed too far—especially with repeated use, high doses, or mixing with alcohol—leaving the liver vulnerable.

But if you:

Take too much acetaminophen in one day,
Use it regularly over time, or
Have low levels of glutathione (which can happen if you drink alcohol frequently, are malnourished, or have certain health conditions),
…then your liver may not be able to keep up. That toxic byproduct, NAPQI, starts to build up. It binds to your liver’s cells, damaging them and, in severe cases, triggering liver failure.

Dr. Melillo says that 4,000 milligrams of acetaminophen per day is the max safe dose for most adults. That’s roughly eight Tylenol PM tablets in 24 hours. It’s surprisingly easy to cross that line—especially since acetaminophen hides in many other over-the-counter meds for cold, flu, or sinus congestion.

Why So Many Americans Face Hidden Risk

Experts estimate that roughly one in three Americans lives with some degree of liver disease—more than 100 million people in total. Many of them may be unknowingly putting further strain on their liver through everyday medications they assume are safe.

The concern grew serious enough that in 2011, the U.S. Food and Drug Administration (FDA) took action. Regulators urged drug manufacturers to cap the amount of acetaminophen in combination medications—such as Tylenol PM—at 325 milligrams per tablet.

The reason was clear: research showed that higher doses offered little added pain relief, yet significantly increased the risk of liver damage.

Despite this, Tylenol PM still delivers 500 milligrams of acetaminophen per pill.

Diphenhydramine: Sleep Now, Side Effects Later

The second active ingredient in Tylenol PM is diphenhydramine, better known as Benadryl. This antihistamine is what causes the sedating effect that helps people fall asleep. However, that drowsiness comes with trade-offs—especially when the drug is used regularly rather than occasionally.

While it may make sleep come easier in the short term, repeated use can carry cognitive and neurological consequences that many users never anticipate.

Diphenhydramine belongs to a class of drugs known as anticholinergics, meaning it interferes with the brain chemical acetylcholine. This chemical plays a critical role in memory, learning, and overall cognitive performance.

When acetylcholine is blocked too frequently or over long periods, problems can emerge. Research has found that individuals who used anticholinergic medications daily for three years or more faced a 54% greater risk of developing dementia compared with those who used them only occasionally.

Diphenhydramine can also cause a range of side effects, including:

Dry mouth

Lightheadedness or dizziness

Confusion, particularly in older adults