Taking Benadryl With Tylenol PM

In our latest question and answer, the pharmacist discusses whether or not Tylenol PM can safely be taken with Benadryl.


I take Tylenol PM mostly every night but it doesn't always work. Can I add Benadryl on top of it for better effects?

Asked by Joseph On Aug 01, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Aug 01, 2022
Last updated Feb 23, 2024

Key points

  • Benadryl and Tylenol PM should not be taken together as both contain diphenhydramine.
  • Taking Benadryl and Tylenol PM together is considered a duplication of therapy, which comes with an increased risk of side effects.


It is not recommended to take Tylenol PM at the same time as Benadryl. Taking these medications together results in duplicate drug therapy of the medication diphenhydramine as both Tylenol PM and Benadryl contain it as an active ingredient. Doses of each should be separated by at least four to six hours.

Tylenol PM

Tylenol PM is a medication that contains:

The pain reliever component of this medication (acetaminophen) is useful for the treatment of mild to moderate pain. The mechanism of acetaminophen is not fully understood but is believed to inhibit prostaglandins which serve a role in inflammation and pain.

The antihistamine component (diphenhydramine) is useful for aiding in sleep or allergic rhinitis symptoms due to the anticholinergic effect that antihistamines exert on the body. This medication, if used as a sleep aid, is recommended to be taken about one hour before the desired hour of sleep.

Each dose (e.g. tablet, capsule) of Tylenol PM contains 500 mg of acetaminophen and 25 mg of diphenhydramine.


Unlike Tylenol PM, Benadryl only contains diphenhydramine which is a 1st generation antihistamine. First-generation antihistamines are known for their sedative effects and relatively short duration of action. The common uses of this medication are for allergy relief, insomnia, and the prevention or treatment of motion sickness. The same anticholinergic, sedating and drowsy side effects are expected with this medication as with Tylenol PM.

Each dose of Benadryl (e.g. tablet, capsule) contains 25 mg of diphenhydramine.

Taking Benadryl With Tylenol PM

The use of these medications together will result in an additive effect of toxicities and not in therapeutic benefit as both medications contain diphenhydramine in the active ingredients. Effects which may be intensified include:

  • Sedation
  • Drowsiness
  • Dry mouth
  • Dry eyes
  • Constipation

When taking either of these medications, it is recommended to take them at night time due to the potential to induce sleep. The use of heavy machinery or operating vehicles is also not recommended while using either of these medications.

Lastly, it is important to note that some sources indicate the dosage of Benadryl for the treatment of insomnia to be 50 mg, or two tablets. Therefore, if necessary, you can safely take one Benadryl tablet with Tylenol PM to equal a dose of 50 mg of diphenhydramine, but this would be the maximum dose. This also isn't generally recommended due to the risk of overdosing using multiple medications.

Final Words

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About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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