Amoxicillin vs. Azithromycin (Z-Pak): Which Is Better, Infection by Infection
Two of the most prescribed antibiotics in the US, from two different drug classes. Here is which one guidelines prefer for strep throat, ear and sinus infections, pneumonia and more, how the dosing differs, what each costs, and where Augmentin fits.
Medically reviewed Medically reviewed by Darcey Melnyk, Pharmacist — NPI 1740713718 · Last updated 2026-10-14
Amoxicillin and azithromycin are two of the most frequently prescribed antibiotics in the US, and it is common to get one when you expected the other. They come from different drug classes, work in different ways and suit different infections. They are not interchangeable, and current guidelines are more specific about which one to use than most people realize. Amoxicillin also has a widely prescribed combination form, Augmentin, covered below.
Amoxicillin (a penicillin) is the guideline first choice for strep throat, ear infections and pneumonia in otherwise healthy adults, and (as Augmentin) for bacterial sinus infections. Azithromycin (a macrolide, the "Z-Pak") is the go-to for penicillin allergy, whooping cough and some STIs, and is taken for just 3 to 5 days. Azithromycin is not stronger; it simply lasts longer in the body. Neither treats a cold, the flu or most bronchitis, which are viral.
At a glance
Amoxicillin
- How it works
- Breaks down bacterial cell walls (kills bacteria)
- First choice for
- Strep throat, ear infections, pneumonia in healthy adults; sinus infections as Augmentin
- Typical course
- 2–3 times a day for 5–10 days
- Penicillin allergy
- Avoid
- Generic
- Yes, very inexpensive
Azithromycin (Z-Pak)
- How it works
- Blocks bacterial protein production (stops growth)
- First choice for
- Whooping cough, penicillin-allergy alternative, chlamydia in pregnancy
- Typical course
- Once a day for 3–5 days, or a single dose
- Penicillin allergy
- Usually the alternative
- Generic
- Yes, very inexpensive
Is azithromycin the same as amoxicillin?
No, and it does not contain amoxicillin. This is one of the most common questions we get at the counter, partly because both are "the antibiotic for a sore throat" in many people's experience.
- Different drug classes. Amoxicillin is a penicillin (a beta-lactam). Azithromycin is a macrolide, related to erythromycin and clarithromycin.
- Different mechanisms. Amoxicillin damages the bacterial cell wall. Azithromycin stops bacteria from making proteins.
- Different bacteria. Azithromycin reaches "atypical" bacteria such as Mycoplasma, Chlamydia and the cause of whooping cough, which amoxicillin does not. Amoxicillin is more reliable against strep and many pneumococci, which are increasingly resistant to macrolides.
- Allergy. A penicillin allergy rules out amoxicillin and Augmentin, but not azithromycin.
Which is better, infection by infection
"Better" depends entirely on the infection. Here is what current US guidelines say. This is general education: your prescriber also weighs your allergies, local resistance, other medicines and whether the infection is bacterial at all.
| Infection | Amoxicillin | Azithromycin | Guideline |
|---|---|---|---|
| Strep throat | First choice (with penicillin) | Alternative for penicillin allergy | IDSA 2012 |
| Ear infection (children) | First choice, high dose; Augmentin if recently treated | Not recommended routinely | AAP 2013 |
| Sinus infection (bacterial) | Preferred, usually as Augmentin | Not recommended first: high macrolide resistance | IDSA 2012 |
| Pneumonia, healthy adult at home | Listed first (high dose) | Only where local resistance is under 25% | ATS/IDSA 2019 |
| Whooping cough (pertussis) | Not used | First choice (macrolides) | CDC |
| Chlamydia | Alternative in pregnancy | Recommended in pregnancy; alternative otherwise (doxycycline preferred) | CDC 2021 |
| Acute bronchitis or a chest cold | Usually neither: almost always viral | CDC | |
| Urinary tract infection | Usually neither; nitrofurantoin, TMP-SMX or fosfomycin are first-line | IDSA | |
The Z-Pak's reputation for sinus infections and bronchitis is out of date. Guidelines now favor amoxicillin-based treatment for bacterial sinusitis and no antibiotic for most bronchitis.
For chlamydia and other comparisons with the tetracycline class, see azithromycin vs. doxycycline.
Dosing: Z-Pak vs. an amoxicillin course
Dosing is where the two look most different, and where the "which is stronger" confusion comes from:
| Regimen | How it's taken | Total drug |
|---|---|---|
| Azithromycin "Z-Pak" | 500 mg on day 1, then 250 mg once daily on days 2–5 (6 tablets) | 1.5 g |
| Azithromycin 3-day | 500 mg once daily for 3 days | 1.5 g |
| Azithromycin single dose | 1 g once (some STIs) | 1 g |
| Amoxicillin, common adult course | 500 mg three times daily, or 875 mg twice daily, for 5–10 days | About 7.5–17.5 g |
| Amoxicillin for strep throat | Once or twice daily for 10 days, per IDSA | About 10 g |
Why a Z-Pak is so short: azithromycin concentrates in tissues and has a tissue half-life of about 68 hours, so it keeps working for days after the last tablet. Amoxicillin has a half-life of about an hour, so it must be taken several times a day. More details are on our azithromycin (Z-Pak) page.
Side effects and safety
| Amoxicillin | Azithromycin | |
|---|---|---|
| Diarrhea, nausea | Common | Common |
| Rash | More common, especially with mono ("mono rash") | Less common |
| Serious allergy | Possible with penicillin allergy | Rare |
| Heart rhythm (QT) | No | FDA warning; caution with heart conditions and QT-prolonging drugs |
| Drug interactions | Few | More: some heart drugs, antacids with aluminum or magnesium, warfarin |
| C. difficile diarrhea | Rare, possible with any antibiotic | Rare, possible with any antibiotic |
| Pregnancy | Commonly used | Commonly used |
The azithromycin heart-rhythm warning comes from a 2013 FDA safety communication. It matters most for people with a known QT problem, a slow heart rate, low potassium or magnesium, or who take other QT-prolonging medicines. See the FDA heart-rhythm warning section of our azithromycin page.
Where Augmentin fits
Augmentin (amoxicillin/clavulanate) is amoxicillin plus clavulanate, which blocks beta-lactamase, an enzyme some bacteria use to destroy amoxicillin. That broader coverage is why it is the guideline choice for bacterial sinusitis and is commonly used for dental infections, animal and human bites, and infections that did not clear with amoxicillin alone.
| Amoxicillin | Augmentin | Azithromycin | |
|---|---|---|---|
| Coverage | Narrower; some bacteria inactivate it | Broader; clavulanate blocks that resistance | Different spectrum, includes atypical bacteria |
| Common adult strength | 500 mg or 875 mg | 875/125 mg twice daily | 250 mg or 500 mg |
| Diarrhea | Present, milder | More common; take with food | Present |
| Penicillin allergy | Avoid | Avoid | Usually OK |
Augmentin vs. azithromycin usually comes up for sinus and dental infections. Augmentin is generally preferred unless there is a penicillin allergy. Full details: Augmentin vs. plain amoxicillin.
What each course costs
All three are inexpensive generics. Here is what pharmacies pay for a typical adult course, from the federal NADAC survey:
Source: CMS NADAC (data.medicaid.gov): amoxicillin 500 mg capsule $0.0788, amoxicillin 875 mg tablet $0.1536, azithromycin 250 mg $0.2656, azithromycin 500 mg $0.5409, amoxicillin/clavulanate 875/125 mg $0.2839 per unit. Retail cash prices are higher and vary by pharmacy.
Cost should almost never be the reason to pick one over the other. If you're paying cash, ask for the generic and a cash quote; it is often less than a typical copay.
Filling an amoxicillin, Augmentin, or azithromycin prescription
All three need a prescription in the US. For why that is and the few genuine over-the-counter exceptions, see can you get antibiotics over the counter?
- Generic by default. We fill generic amoxicillin, amoxicillin/clavulanate and azithromycin unless your prescriber writes brand-only. Same active ingredient, far lower price.
- Allergy and interaction check. Tell us about any penicillin allergy and your full medication list. We check azithromycin against heart-rhythm and other interacting drugs before it leaves the counter.
- Same-day and delivery. Call us at (860) 522-9289 and we'll have a new antibiotic ready quickly, or use our free next-day delivery in the Hartford area.
Azithromycin (Zithromax) · Augmentin · Doxycycline · Azithromycin vs. doxycycline · Antibiotics over the counter
Frequently asked questions
Is azithromycin the same as amoxicillin?
No. Azithromycin is a macrolide and amoxicillin is a penicillin. They are different molecules from different drug classes, kill or stop bacteria in different ways, and cover a different mix of bacteria. Azithromycin contains no amoxicillin or penicillin, which is why it is a common choice for people with a penicillin allergy.
Which is better for a throat infection or strep throat?
For strep throat, amoxicillin (or penicillin) is the first-line choice in national guidelines for people without a penicillin allergy. Azithromycin is an alternative for people who are allergic to penicillin. Many sore throats are viral and need no antibiotic at all, which is why a strep test comes first.
Which is better for a sinus infection?
Most sinus infections are viral and clear on their own. When an antibiotic is needed, the IDSA guideline recommends amoxicillin/clavulanate (Augmentin), and pediatric guidelines also allow plain amoxicillin. It advises against azithromycin for initial treatment because many of the bacteria involved are now resistant to macrolides, even though azithromycin is FDA-approved for sinusitis.
Which is better for pneumonia?
For otherwise healthy adults treated at home, the 2019 ATS/IDSA guideline lists high-dose amoxicillin first, with doxycycline, or azithromycin only where local resistance is low. People with heart, lung or kidney disease, diabetes or other risk factors usually get a combination or a different antibiotic. This is a prescriber decision based on your exam and history.
Can I take azithromycin if I am allergic to amoxicillin?
Usually, yes. Azithromycin is not a penicillin, and penicillin allergy does not carry over to macrolides. It is one of the standard alternatives for penicillin-allergic patients. Always tell your prescriber and pharmacist about the allergy and what reaction you had.
Z-Pak vs. amoxicillin: what is the difference?
A Z-Pak is a 5-day pack of azithromycin: 500 mg on day 1, then 250 mg a day for 4 days, six tablets in all. Amoxicillin is usually taken two or three times a day for 5 to 10 days. The Z-Pak is shorter because azithromycin stays in your tissues for days, not because it is stronger.
Why is azithromycin only taken for 3 or 5 days?
Azithromycin has a tissue half-life of about 68 hours, so it keeps working for days after the last tablet. Amoxicillin clears in about an hour, which is why it is taken several times a day for longer.
Is azithromycin 250 mg stronger than amoxicillin 500 mg?
The numbers cannot be compared. They are different drugs with different potencies and dosing schedules. A Z-Pak delivers 1.5 grams of azithromycin over 5 days, while a typical amoxicillin course delivers roughly 7 to 17 grams. What matters is whether the drug covers your infection.
Can I take amoxicillin if azithromycin didn't work, or vice versa?
Only if your prescriber decides that is appropriate. They target different mechanisms and different bacteria, so switching is not automatic, and if a first antibiotic failed, your prescriber may want to recheck the diagnosis rather than assume a different antibiotic is simply the fix.
Is Augmentin the same as amoxicillin?
No, but it is closely related. Augmentin is amoxicillin combined with clavulanate, an ingredient that blocks a resistance enzyme some bacteria use to destroy amoxicillin. That lets Augmentin cover some bacteria plain amoxicillin cannot, which is why it is often used for sinus, dental and bite infections, or when amoxicillin alone did not work.
Which has more side effects?
Both commonly cause diarrhea, nausea and stomach upset. Amoxicillin causes more rashes and can trigger a true penicillin allergy. Azithromycin can affect heart rhythm (QT prolongation) and interacts with more medicines, which matters for people with heart conditions. Augmentin causes more diarrhea than plain amoxicillin.
Can I drink alcohol while taking amoxicillin, Augmentin, or azithromycin?
None of these three has a dangerous direct interaction with alcohol the way metronidazole does. Alcohol can still worsen stomach side effects and dehydration while you are fighting an infection, so moderation or avoidance is the safer choice until you finish the course.
How much does each cost without insurance?
Both are inexpensive generics. CMS data puts the pharmacy acquisition cost of a typical adult course at about $2 to $3 for amoxicillin and about $1.60 for a Z-Pak. Generic Augmentin costs pharmacies about $5.70 for a 10-day course. Retail cash prices are higher and vary, so ask us for a quote.
Sources
- Amoxil (amoxicillin) prescribing information: dosing and pharmacokinetics — U.S. Food and Drug Administration
- Zithromax (azithromycin) prescribing information: indications, dosing, 68-hour half-life, QT warning — U.S. Food and Drug Administration
- Augmentin (amoxicillin/clavulanate) prescribing information — U.S. Food and Drug Administration
- Shulman ST, et al. Clinical practice guideline for group A streptococcal pharyngitis: 2012 update by the IDSA. Clin Infect Dis. 2012;55(10):e86-e102 — Infectious Diseases Society of America
- Chow AW, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54(8):e72-e112 — Infectious Diseases Society of America
- Lieberthal AS, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131(3):e964-e999 — American Academy of Pediatrics
- Metlay JP, et al. Diagnosis and treatment of adults with community-acquired pneumonia: ATS/IDSA guideline. Am J Respir Crit Care Med. 2019;200(7):e45-e67 — American Thoracic Society / IDSA
- Sexually Transmitted Infections Treatment Guidelines, 2021: Chlamydial infections — CDC
- Pertussis (whooping cough): treatment — CDC
- Chest cold (acute bronchitis): antibiotics are not needed — CDC
- NADAC (National Average Drug Acquisition Cost), survey dates 2026-09-23 to 2026-10-07 — CMS
- Antibiotic Resistance Threats in the United States — CDC