Azithromycin (Z-Pak) vs amoxicillin: antibiotics compared
Azithromycin, often given as a five-day Z-Pak, and amoxicillin are two of the most prescribed antibiotics. Amoxicillin is the first choice for most ear, sinus and strep throat infections; azithromycin covers different bacteria, such as those behind some pneumonias and chlamydia, and is an option for some people with a penicillin allergy.
Updated October 4, 2026
At a glance
- Antibiotic family
- Azithromycin
- Macrolide
- Amoxicillin
- Penicillin
- Course
- Azithromycin
- Usually once a day for 3 to 5 days
- Amoxicillin
- Usually two or three times a day for 5 to 10 days
- First choice for
- Azithromycin
- Some pneumonias, chlamydia, some people with penicillin allergy
- Amoxicillin
- Ear infections, sinus infections, strep throat
- Heart rhythm caution
- Azithromycin
- Yes
- Amoxicillin
- No
- Generic
- Azithromycin
- Yes
- Amoxicillin
- Yes
Azithromycin Zithromax, Z-Pak | Amoxicillin | |
|---|---|---|
| Antibiotic family | Macrolide | Penicillin |
| Course | Usually once a day for 3 to 5 days | Usually two or three times a day for 5 to 10 days |
| First choice for | Some pneumonias, chlamydia, some people with penicillin allergy | Ear infections, sinus infections, strep throat |
| Heart rhythm caution | Yes | No |
| Generic | Yes | Yes |
Why the short course is not always better
Azithromycin’s once-a-day, five-day course is convenient because it stays in the body for days after the last dose. But many strep and ear infection bacteria are now resistant to it, so amoxicillin is usually the more reliable choice for those infections. Matching the antibiotic to the likely bacteria matters more than the length of the course.
Penicillin allergy
For people with a penicillin allergy, azithromycin is one alternative, though resistance limits it for some infections, and other options exist. Many penicillin allergy labels turn out to be wrong when tested, which is worth discussing with your clinician.
Side effects and cautions
Both commonly cause diarrhea and nausea, and severe or bloody diarrhea, even weeks later, needs prompt care. Azithromycin can affect heart rhythm, so care is needed with other drugs that do and in people with heart rhythm problems. Amoxicillin more often causes a rash, which is not always an allergy.
Not for viruses
Neither treats colds, flu or most sore throats and coughs, which are viral. Taking an antibiotic you do not need adds side effects and resistance without benefit.
Cost
Both are inexpensive generics. Children’s liquids usually cost more than tablets or capsules.
Missed doses
Take a missed dose as soon as you remember unless the next one is near, and never double up. Finish the course as prescribed even if you feel better.
Questions for your prescriber
- Is this infection likely to be bacterial, and which antibiotic covers it?
- Is my penicillin allergy label accurate?
- Do I have any heart rhythm risks?
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Sources
Written by the Script Unlock editorial team from the sources above. It is general information, not advice for you or your pet; your prescriber decides which medicine is right.
Script Unlock is a marketplace that lets licensed pharmacies quote a cash price on your prescription. It does not prescribe, dispense or sell medication, does not process patient payments, and does not give medical advice. Always follow the instructions of your prescriber and pharmacist and read the medication guide supplied with your medicine.