ZzzQuil On Retail Shelf With Text - With Benzonatate Interaction


There is a potential issue with combining benzonatate and ZzzQuil in that the risk of side effects occurring can increase, notably, side effects like sedation and dizziness.

This problem, however, would generally be considered mild since ZzzQuil is intended to be used in the evening, as a night-time sleep aid. Therefore, feeling a little more tired than usual likely isn't going to be much of a concern.

Fortunately, some of the major and dangerous side effects of some sedatives (e.g. benzodiazepines and barbiturates), like respiratory depression, aren't associated with benzonatate. Respiratory depression has been associated with diphenhydramine (the active ingredient in ZzzQuil), but generally only in cases of overdose.

Overall, if you need to be alert and would be performing tasks that require mental acuity, you certainly shouldn't combine the two drugs. If you just plan on calling it a night, there isn't much concern.

The next sections describe ZzzQuil and benzonatate in a little more detail.

What Is ZzzQuil?

ZzzQuil Liquid And LiquCaps On Wooden Table

ZzzQuil is a product by the makers of NyQuil that is intended to be used as a night-time sleep aid. It contains the active ingredient diphenhydramine, which is also the active ingredient in Benadryl.

Diphenhydramine is a first-generation, sedating antihistamine. First-generation antihistamines are noted for their short duration of action (when compared to second-generation ones like Claritin) and their sedative effects.

Diphenhydramine specifically lasts around four to six hours per dose, with peak effects occurring around 30-60 minutes after taking.

When used as a sleep aid, it has been known to cause next-day drowsiness, but it is generally uncommon due to the short duration of action. It is more likely to happen in older adults and in those with liver dysfunction.

While ZzzQuil was initially only a single product containing diphenhydramine, there recently has been a family of ZzzQuil products made available on the market, including:

  • ZzzQuil Liquid (diphenhydramine)
  • ZzzQuil Pure Zzzs De-Stress Sleep Gummies (Melatonin + various botanicals)
  • ZzzQuil Pure Zzzs Beauty Sleep Gummies (Melatonin + various botanicals)
  • Vicks PURE Zzzs De-Stress & Sleep Tablets (Melatonin + various botanicals)
  • ZzzQuil Pure Zzzs Kidz Gummies (Melatonin + Chamomile + Lavender)
  • PURE Zzzs Soothing Aromatherapy Balm

Original ZzzQuil liquid is the only one that contains a pharmaceutical agent (diphenhydramine) and comes in several varieties, including:

  • ZzzQuil Warming Berry Liquid
  • ZzzQuil Soothing Mango Berry Alcohol-Free Liquid
  • ZzzQuil LiquiCaps
  • ZzzQuil Calming Vanilla Cherry Liquid

In considering the interaction mentioned in this question (with benzonatate), I am using the ZzzQuil products containing diphenhydramine.

What Is Benzonatate?

Benzonatate Perles Spilling Onto Table From White Bottle

Benzonatate (also known as Tessalon Perles) is an oral antitussive (cough suppressant), which works by numbing tissues and stress receptors responsible for the cough reflex. Data also suggests it may work centrally (i.e. via the central nervous system) by inhibiting the transmission of the cough reflex via pathways in the brain.

The onset of action is fairly quick after taking a dose, and you should begin to feel effects within 15 to 20 minutes. The prescribing information for the drug states that its effect last for 3 to 8 hours.

Benzonatate is fairly well tolerated, especially when compared to narcotic cough suppressants, like codeine.

In fact, one of its notable features is the lack of adverse reactions. Narcotic cough medications have the risk (especially with overdose) of causing respiratory depression and shallow breathing. This is of definite concern in those with preexisting breathing problems and in those taking other medications that may do the same (e.g. benzodiazepines).

Nevertheless, it can cause sedation in individuals taking the drug and is the most commonly reported side effect (along with dizziness, headache, and GI upset).


Drug Interaction Q Mark

As stated in the 'Overview' section, the only 'interaction' between ZzzQuil and benzonatate is that taking both can increase the risk of sedative side effects, since these side effects are associated with both drugs.

Seeing as to how ZzzQuil is a sleep aid and is intended to make you tired, that concern of increased sedation isn't something that would preclude their use together (as long as you plan on going to bed).

There is no indication that the risk of serious side effects, like respiratory depression, is increased when using benzonatate and ZzzQuil.


Taking ZzzQuil (diphenhydramine) and benzonatate together may result in additive side effects, such as dizziness and sedation. Nevertheless, since ZzzQuil is intended to be used as a sleep-aid, the interaction isn't of much clinical significance for most.

  1. Benzonatate Prescribing Information. AccessFDA
  2. Benzonatate Drug Monograph. ClinicalKey (Subscription Required)
  3. Diphenhydramine Drug Monograph. ClinicalKey (Subscription Required)