It is not safe to take ZzzQuil with NyQuil as both contain sedating "first generation" antihistamines. Using both together would be considered a therapeutic duplication and can increase the risk of side effects. ZzzQuil contains diphenhydramine, the same active ingredient in Benadryl. NyQuil contains doxylamine, also a sedating "first generation" antihistamine.

Interaction Between NyQuil and ZzzQuil

  • Both NyQuil and ZzzQuil contain sedating, "first generation" antihistamines. Using both would be considered a therapeutic duplication and increases the risk of side effects.
  • Both drugs cause CNS (central nervous system) depression, which may result in a decrease in blood pressure and severe drowsiness. In combination with other CNS depressants, dangerous side effects such as respiratory depression are possible.

Dosing Recommendations

Only take the NyQuil at bedtime if you need it for trouble sleeping and you are experiencing multiple cold symptoms. NyQuil is a combination medication that contains the following ingredients:

  • Acetaminophen (analgesic)
  • Dextromethorphan (cough suppressant)
  • Doxylamine (sedating antihistamine)

ZzzQuil contains only doxylamine as its active ingredient and should generally just be used as a sleep aid although it can help certain cold symptoms such as a runny nose and post nasal drip.

While you shouldn't take NyQuil and ZzzQuil together, you can take DayQuil and ZzzQuil together. DayQuil contains the following ingredients:

  • Acetaminophen (analgesic)
  • Dextromethorphan (cough suppressant)
  • Phenylephrine (nasal decongestant)

Taking DayQuil during the day and ZzzQuil at bedtime is safe.


Do not take the ZzzQuil and Nyquil together due to them both containing a sedating first generation antihistamine (diphenhydramine and doxylamine respectively).

It is important to note that it is recommended that you do not you use sleep aids for more than 2 weeks because it can alter your normal sleep patterns. If you still cannot sleep without medication after the 2 weeks, please contact your doctor. Be sure to always read the ingredients on cold medication to ensure that you are not taking too much of the same drug or two drugs treating the same symptom.

Drink plenty of water while on these medications and do not drive or operate machinery while taking NyQuil or ZzzQuil.