Can You Take Tylenol PM With Alprazolam?

In our latest question and answer, the pharmacist discusses whether or not it is safe to take Tylenol PM with alprazolam (Xanax).

Apr 07, 2018

Paul asked

Can you take Tylenol PM and alprazolam together?


There are no major drug interactions between Tylenol PM and alprazolam and they can be taken together in certain situations. However, concurrent use of Tylenol PM and alprazolam should be done with caution, due to both medications being CNS (central nervous system) depressants.

Specifically, we are concerned about the diphenhydramine contained in Tylenol PM and alprazolam. As mentioned above, both are CNS depressants and can cause additive sedation when used together. Rarely, the combination could cause confusion and respiratory depression.

In most cases, Tylenol PM and alprazolam should be dosed apart from one another to avoid the additive sedative effects. For most individuals, it would be considered safe to take alprazolam during the day and take Tylenol PM only at night as a sleep aide.

For those who have been on a consistent dose of alprazolam for extended periods of time, it may be okay to take it with Tylenol PM at the same time, but you should speak with your doctor before doing so.

Tylenol PM

Tylenol PM is a combination product that contains:

  • Acetaminophen (brand name is Tylenol)
  • Diphenhydramine (the common brand name is Benadryl)

Tylenol PM is commonly used as a pain reliever and/or sleep aid. Acetaminophen is a centrally acting analgesic and antipyretic that is effective at relieving pain and reducing fever.

Diphenhydramine is a first generation antihistamine. Diphenhydramine can be used for several indications including:

  • Allergies or allergic reaction
  • Cold/flu symptoms
  • Sleep aid
  • Motion sickness

Side effects of diphenhydramine include drowsiness, confusion, dizziness, and dry mouth.


Alprazolam (brand name Xanax) is a benzodiazepine that is commonly used to treat anxiety. Alprazolam is also a CNS depressant and can have side effects including drowsiness/sedation, confusion, and dizziness.


There are no major drug interactions between Tylenol PM and alprazolam; however, alprazolam and diphenhydramine (from Tylenol PM) are both CNS depressants.

Concurrent use may increase the chance of side effects, such as increased drowsiness, sedation, or confusion. These agents should be used in combination with caution.

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