Is Valacyclovir Safe To Take With Acetaminophen And Guaifenesin?

In our latest question and answer, Dr. Brian Staiger answers a drug interaction question regarding the drug valacyclovir.


I am on valacyclovir for shingles and I developed a pressure headache. Not sure if it's the drug or the sinus/ear congestion I'm prone to. Can I take acetaminophen or guaifenesin with valacyclovir? (Not Mucinex -- a generic bottle of just guaifenesin.) Any side effects from combining? Thanks!

Asked by Julia On Dec 25, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Dec 27, 2022
Last updated Jul 23, 2024

Key points

  • There is no known drug interaction between acetaminophen, guaifenesin, and valacyclovir.


Thanks for reaching out! There is no known drug interaction between any of the drugs you listed in your question (valacyclovir, acetaminophen, guaifenesin). They are all considered safe to combine.

Now, you mentioned not knowing if the headache you are experiencing is a side effect from valacyclovir (generic for Valtrex), or if you are just coming down with something.

Headaches Are A Common Side Effect Of Acyclovir

It is important to note that experiencing a headache while taking valacyclovir is one of the most common side effects of the drug.

A little over 11% of individuals taking part in clinical trials for the drug experienced a headache. The other most common side effects were nausea, pharyngitis, and diarrhea.

Sinus Headache Or From Acyclovir?

Although it can be tough to tell whether or not a headache is due to sinus pressure or other causes, there are a few common characteristics of sinus headaches to look for:

  • Location: A sinus headache is typically characterized by pain and pressure in the forehead, cheeks, or bridge of the nose. A regular headache may be felt in other parts of the head, such as the temples or the back of the head.
  • Duration: A sinus headache is usually associated with a sinus infection or other sinus problem and will last as long as the underlying problem exists. A regular headache may be shorter in duration and may resolve on its own.
  • Associated symptoms: A sinus headache may be accompanied by other symptoms such as nasal congestion, a runny nose, or a fever. A regular headache may not have any associated symptoms.

Regardless of what is causing your headache, as mentioned, acetaminophen (generic Tylenol) and guaifenesin (generic Mucinex) are safe to take with valacyclovir.

Additionally, if you do think your headache is from a sinus problem, a nasal decongestant may provide you with some benefits as well.

Final Words

Thanks so much for reaching out to us! Contact us again anytime.


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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