Can You Take A Z-Pak If You Have A Penicillin Allergy?

In our latest question and answer, the pharmacist discusses the safety of taking a Z-Pak if you have a penicillin allergy.


I was told that I had an allergic reaction to penicillin when I was a child. I have it on my medical record. I was just given a Zpak. Is it ok to take due to my penicillin allergy?

Asked by Marie On Oct 04, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Oct 04, 2022
Last updated Jun 14, 2024

Key points

  • Studies show that there is no cross-reactivity between penicillin-type antibiotics and macrolides (the drug class of azithromycin, the antibiotic in a Z-Pak). If you are allergic to penicillin, azithromycin is safe to use.


Thanks so much for reaching out! I'll provide some more detail in the sections below, but yes, azithromycin (Z-Pak) is typically fine to take if you have a documented penicillin allergy. These antibiotics are in different drug classes and studies have shown there is no cross-reactivity between them.

Azithromycin And Penicillin Are Different Types Of Antibiotics

As mentioned, the two antibiotics in question here are in different drug classes.

Penicillin is a penicillin-type antibiotic, while azithromycin is a macrolide antibiotic.

While it is true that some sensitivities/allergies can cross over between drug classes (penicillin-type drugs and cephalosporins are a good example of that). Several studies have confirmed that if a patient is allergic to penicillin, a macrolide, like azithromycin, may be a good choice:

This antibiotic [azithromycin] is therefore a valid alternative to penicillin and/or cephalosporin in patients allergic to these two drugs.

Depending on what you are being treated for, you likely have a number of antibiotic options if you can't take penicillin (e.g. Macrolides, tetracycline, fluoroquinolones, sulfamethoxazole etc...). Be sure to let your doctor and pharmacy know of your allergies, so if penicillin were to be prescribed, your allergy can be noted and an alternative antibiotic be given.

Final Words

Thanks again for contacting us! Please do so again anytime.


  • [Safety of azithromycin in patients allergic to penicillin and cephalosporin], PubMed
  • A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis, PubMed
  • Penicillin susceptibility and macrolide-lincosamide-streptogramin B resistance in group B Streptococcus isolates from a Canadian hospital, PubMed

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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