Taking NyQuil WIth Azithromycin (Z-Pak)

In our latest question and answer, the pharmacist discusses whether or not it is safe to take NyQuil and azithromycin (Z-Pak) together.


I started with my first dose of Azithromycin today, two 250mg around 6 hours ago. Can I take Nyquil tonight before bed?

Asked by TJS On Nov 23, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Nov 23, 2022
Last updated Jun 07, 2023

Key points

  • There is no known interaction between azithromycin (the antibiotic contained in a Z-Pak) and the drugs contained in NyQuil.


There is no known drug interaction between azithromycin (Z-Pak) and Nyquil (acetaminophen, dextromethorphan, and doxylamine). They can be safely taken together.

'NyQuil Severe', which contains one additional ingredient when compared to the 'original' NyQuil, is also safe to take with a Z-Pak.

Below, I discuss each medication in more detail

Information About The Z-Pak

A Z-pak consists of six tablets of azithromycin 250 mg. Most commonly, it is prescribed to be taken as follows:

  • Take two tablets (500mg) by mouth on the first day of therapy
  • Take one tablet (250mg) by mouth for the following four days

Azithromycin, the antibiotic in the Z-Pak, is a macrolide antibiotic that can treat a variety of infections including bronchitis, sinus infections, ear infections, skin infections, sexually transmitted infections, and more.

Azithromycin can cover several types of bacteria but is not effective in treating the flu, the common cold, or other viral infections.

Like most antibiotics, azithromycin may cause diarrhea, nausea, vomiting, and abdominal pain. Macrolides are more likely to cause these types of side effects, but azithromycin is one of the more tolerable drugs in the class.

Another concern with azithromycin is that it can cause QT prolongation (a type of arrhythmia) in patients with a past medical history related to the heart. Drug interactions can also be a concern so always check each new medication prior to starting a new therapy. 

Information About Nyquil

Nyquil comes in a variety of formulations and contains several different ingredients. Nyquil Cold & Flu contains the following:

  • Acetaminophen (pain relief, fever reducer)
  • Dextromethorphan (cough suppressant)
  • Doxylamine (antihistamine)

 'NyQuil Severe' adds on a nasal decongestant, phenylephrine.

Acetaminophen is an analgesic that can be taken for a wide variety of acute and chronic pain ailments. Acetaminophen has a half-life of 2-3 hours. About 85-98% of the drug gets absorbed and it reaches peak concentrations within 30-60 minutes.

Typically, acetaminophen can start working within 15 minutes. Acetaminophen can have negative impacts on the liver, especially at higher doses for an extended period of time.

Dextromethorphan (commonly referred to as DM on many over-the-counter products) is a cough suppressant that reduces the urge to cough. It is best to prevent a bothersome dry cough or a cough that doesn’t involve mucus from the lower respiratory system.

Doxylamine is a first-generation antihistamine that is more likely to cause sedation and drowsiness as compared to second-generation antihistamines (i.e., loratadine, cetirizine).

Other first-generation antihistamines include Benadryl (diphenhydramine), Dramamine (dimenhydrinate), Chlor-Trimeton (chlorpheniramine), Tavist (clemastine), and Phenergan (promethazine), among others. 

Final Words

NyQuil often represents a good medication choice for those suffering from a variety of symptoms that may come about from an infection, such as a fever, body aches, congestion, and a cough.

As mentioned, NyQuil (and NyQuil Severe) are safe to take with azithromycin.

Thanks for your question!


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 Hello@HelloPharmacist.com! You can also connect with Dr. Brian Staiger on LinkedIn.

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