Azithromycin vs. amoxicillin: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

If you have ever experienced a bacterial sinus infection or a variety of other types of bacterial infectious diseases, chances are you have taken an antibiotic. Azithromycin and amoxicillin are two common antibiotics used in the treatment of bacterial infections. Antibiotics are prescription medications used to treat bacterial infections—they will not work for viral infections such as the flu, common cold, or COVID-19.

Azithromycin is also known by its brand name Zithromax (you may have heard of a Zithromax Z-Pak, which is commonly prescribed). It is classified in a group of medications called macrolide antibiotics. Azithromycin works by binding to the bacteria and preventing the bacteria from producing proteins that it needs to survive. Azithromycin is commonly used to treat bacterial infections like sinus infections, pneumonia, and certain sexually transmitted diseases, to name a few.

Amoxicillin is known by its brand name Amoxil, and it is classified in a group of medications called penicillin (or beta-lactam) antibiotics. Amoxicillin works by preventing bacteria from forming cell walls, which kills the bacteria. Amoxicillin is commonly used to treat bacterial infections such as ear infections, pneumonia, and throat infections, among others.

Both medications are approved by the United States Food and Drug Administration (FDA). Although both medications are antibiotics, they have many differences. Continue reading to learn more about azithromycin and amoxicillin.

What are the main differences between azithromycin and amoxicillin?

Azithromycin is a macrolide antibiotic, known by its brand name Zithromax. Zithromax is made by Pfizer. Azithromycin is commonly prescribed as a tablet, in the form of a Zithromax Z-Pak (a six-tablet, 5-day course of azithromycin) or Zithromax Tri-Pak (a 3-day course of azithromycin). Used in both adults and children, the dosage varies by indication.

Amoxicillin is a penicillin antibiotic, known by its brand name Amoxil. However, Amoxil is no longer commercially available, and the medication is only available in the generic form. Amoxicillin is most commonly prescribed as amoxicillin capsules, or as a combination drug that also contains clavulanic acid (to prevent resistance) as Augmentin. Amoxicillin is commonly used in adults and children, and the dosage varies by indication. This article will focus on amoxicillin, not Augmentin unless noted. 

It’s important to note that when you are prescribed an antibiotic, you should take it as directed, and finish the full course of treatment, even if you start to feel better. However, if you have been taking an antibiotic for several days and you feel worse or are not feeling any better, contact your healthcare provider for guidance.

Main differences between azithromycin and amoxicillin
	Azithromycin	Amoxicillin
Drug class	Macrolide antibiotic	Penicillin antibiotic
Brand/generic status	Brand and generic	Generic
What is the brand name?	Zithromax	Amoxil (no longer available in the brand name)
What form(s) does the drug come in?	Tablets, suspension, injection, powder packet, eye drops (AzaSite)	Capsule, suspension, tablet, chewable tablet Also: tablet, chewable tablet, and suspension in combination with clavulanic acid (amoxicillin-clavulanate) as Augmentin; in combination with lansoprazole and clarithromycin as Prevpac
What is the standard dosage?	Z-Pak: 2 tablets by mouth on day 1, then 1 tablet daily on days 2 through 5	Varies; example: 500 mg by mouth 3 times a day for 10 days
How long is the typical treatment?	5 days; varies	7-10 days; varies
Who typically uses the medication?	Adults and children	Adults and children

Conditions treated by azithromycin and amoxicillin

Azithromycin is used to treat a variety of bacterial infections in adults and children (see list below). It should not be used in people with pneumonia who have cystic fibrosis, nosocomial (hospital-acquired) infections, known or suspected bacteremia (bacteria in the blood), hospitalized patients, older adult or debilitated patients, or patients with a compromised immune system or asplenia (no spleen).

• Acute bacterial exacerbations of chronic bronchitis (acute bronchitis) from Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
• Acute sinusitis from Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
• Community-acquired pneumonia from Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae (adults and children older than 6 months)
• Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in patients who cannot use first-line therapy (adults and children older than 2 years)
• Uncomplicated skin/skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae
• Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae
• Genital ulcer disease in men due to Haemophilus ducreyi (chancroid)
• Acute ear infection (acute otitis media, or middle ear infections) (>6 months of age) caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae

Amoxicillin is also used to treat a variety of bacterial infections:

• Ear/nose/throat infections caused by certain strains of Streptococcus pneumoniae, Staphylococcus spp., or H. influenzae
• Urinary tract infections from E. coli, P. mirabilis, or E. faecalis
• Skin or skin structure infections caused by certain strains of Streptococcus, Staphylococcus, or E. coli
• Acute lower respiratory tract infections due to certain strains of Streptococcus, S. pneumoniae, Staphylococcus, or H. influenzae
• Acute uncomplicated gonorrhea in males and females due to N. gonorrhoeae
• Eradication of H. pylori to lower the risk of duodenal ulcer recurrence
• Amoxicillin is also used as triple therapy with lansoprazole and clarithromycin (as Prevpac) in patients with H. pylori infection and duodenal ulcer

To reduce the development of antibiotic resistance, azithromycin or amoxicillin should only be used in bacterial infections when determined to be appropriate by your doctor. In fact, the Centers for Disease Control and Prevention (CDC) is promoting the appropriate use of antibiotics by helping healthcare providers choose the right antibiotic (including the right dose and duration) and reduce unnecessary antibiotic use. This is called antibiotic stewardship.

Is azithromycin or amoxicillin more effective?

When considering which drug is more effective, it’s important to look at what the drug is being used to treat. For example, where is the infection? What bacteria is causing the infection? As you can see in the list of indications, each antibiotic can treat a wide variety of infections caused by certain bacteria.

One study compared a single dose of azithromycin to a 10-day regimen of amoxicillin-clavulanate (Augmentin) for children with middle ear infections. The researchers found both drugs to be effective and well-tolerated. A 2021 meta-analysis (analysis of many studies) looked at azithromycin vs Augmentin for middle ear infections in children and concluded that although both drugs are effective, azithromycin may be safer and better tolerated. 

Another study done in Brazil looked at approximately 100 patients with infectious exacerbation of chronic obstructive pulmonary disease. The study found both drugs to be effective and well-tolerated.

Both azithromycin and amoxicillin are very commonly prescribed and generally well-tolerated. If you think you have a bacterial infection, see your healthcare provider as soon as possible. They can examine and assess your need for antibiotics and determine which one is most appropriate for you based on your symptoms and medical history, along with other drugs you take that may interact with azithromycin or amoxicillin.

Coverage and cost comparison of azithromycin vs. amoxicillin

Azithromycin is usually covered by insurance plans and Medicare prescription plans. A typical prescription would be for a generic Z-Pak, and the out-of-pocket cost without insurance would be about $32 per for a 6-tablet package. With SingleCare, the price starts at $4 for a 6-tablet package at participating pharmacies.

Amoxicillin is also usually covered by insurance plans and Medicare prescription plans. A typical prescription would be for 21 capsules of amoxicillin 500 mg, and the out-of-pocket price without insurance would be approximately $19. It’s as low as $1 per 21, 500 mg capsules with a SingleCare coupon.

Get the SingleCare prescription discount card

	Azithromycin	Amoxicillin
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare prescription plans?	Yes	Yes
Standard dosage	1 Z-Pak (#6, 250 mg tablets)	#21, 500 mg capsules
SingleCare cost	$4 per 1 package of 6 tablets	$1 per 21, 500 mg capsules

Common side effects of azithromycin vs. amoxicillin

The most common side effects of azithromycin are diarrhea, nausea, and abdominal pain. Other side effects, which are less common, and occur in less than 1% of patients, include vomiting, flatulence, dizziness, headache, sleepiness, and rash.

The most common side effects of amoxicillin are related to penicillin sensitivity. They include nausea, vomiting, diarrhea, a black/hairy tongue, and rash/hypersensitivity reactions. Percentages are not available relating to occurrence rates.

In general, with antibiotic therapy, you may be more susceptible to a yeast infection. Ask your healthcare provider if you should take a probiotic.

This is not a full list of side effects. Other side effects may occur. Consult your healthcare provider for a full list of potential adverse events.

	Azithromycin		Amoxicillin
Side effect	Applicable?	Frequency	Applicable?	Frequency
Diarrhea/loose stools	Yes	4-5%	Yes	>1%
Nausea	Yes	3%	Yes	>1%
Abdominal pain	Yes	2-3%	Yes	Not reported
Vomiting	Yes	<1%	Yes	>1%
Rash	Yes	<1%	Yes	>1%

Source: DailyMed (azithromycin), DailyMed (amoxicillin), FDA label (amoxicillin).

Drug interactions of azithromycin vs. amoxicillin

Taking either azithromycin or amoxicillin in combination with an anticoagulant (blood thinner) such as warfarin may increase the risk of bleeding, which can be life-threatening. If this combination is prescribed, patients should be closely monitored during antibiotic treatment. 

Oral contraceptives (birth control pills), when taken in combination with antibiotics, can be less effective. Consult your healthcare provider about the need for effective backup birth control to prevent pregnancy, such as a condom, while you are on an antibiotic.

Azithromycin drug interactions may also occur with digoxin or colchicine. Drugs that prolong the QT interval, including certain antiarrhythmics, should not be taken with azithromycin due to the risk of life-threatening or fatal arrhythmia.

Allopurinol in combination with amoxicillin can lead to a greater incidence of rash.

This is not a complete list of drug interactions. Other drug interactions may occur. Consult your healthcare provider for professional medical advice.

Drug	Drug Class	Azithromycin	Amoxicillin
Warfarin	Anticoagulants	Yes	Yes
Allopurinol	Xanthine oxidase inhibitor (used for gout)	No	Yes
Oral contraceptives	Oral contraceptives	Yes	Yes
Nelfinavir	Protease inhibitor	Yes	No
Digoxin	Cardiac glycosides	Yes	No
Colchicine	Anti-gout agent	Yes	No
Maalox Mylanta	Antacids	Yes	No
Amiodarone Dofetilide Procainamide Quinidine Sotalol	Antiarrhythmics	Yes	No
Amitriptyline Desipramine Fluoxetine Haloperidol Methadone Quetiapine Sertraline Zolmitriptan	Drugs that prolong the QT interval	Yes	No

Warnings of azithromycin and amoxicillin

Warnings of azithromycin:

• You should not take azithromycin if you are allergic to azithromycin, erythromycin, or any macrolide antibiotic; or if you have a history of liver problems from prior use of azithromycin.
• Serious allergic or skin reactions may occur. Fatalities have been reported. If an allergic reaction occurs, you should stop the drug immediately and seek emergency treatment. Symptoms of a serious allergic reaction may include hives, difficulty breathing, or swelling of the face, lips, tongue, or throat. Symptoms of a serious skin reaction may include fever, burning eyes, sore throat, blistering or peeling skin, or red or purple rash. 
• Liver problems have occurred, some of which have been fatal. Stop azithromycin immediately if symptoms of hepatitis (fatigue, jaundice, abdominal pain, itching) occur, and seek emergency treatment. (Jaundice is a yellowing of the skin and whites of the eyes.)
• Infantile Hypertrophic Pyloric Stenosis has been reported in neonates (<42 days old). Contact your physician if your baby is vomiting or has irritability when feeding.
• Macrolide antibiotics, including azithromycin, may cause a prolongation of the QT interval, increasing the risk of arrhythmias. Certain patients are at higher risk, including patients with a history of arrhythmia/torsades de pointes or other heart problems, patients on drugs that can prolong the QT interval, older adults, and patients with uncorrected low potassium or magnesium.
• Azithromycin may exacerbate symptoms of myasthenia gravis or may be associated with a new onset of myasthenia gravis.
• Patients with sexually transmitted urethritis or cervicitis should be tested for syphilis and gonorrhea, and be treated appropriately if there is an infection.

Warnings of amoxicillin:

• Do not use amoxicillin if you have had a history of allergic reactions to penicillin, ampicillin, Augmentin, or amoxicillin.
• Serious, occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported. This can occur in patients who are being treated with cephalosporins such as cefdinir or cephalexin), too. Patients should not be prescribed amoxicillin if there has been a previous reaction. If an allergic reaction occurs, amoxicillin should be stopped and you should seek emergency treatment.

Warnings for both azithromycin and amoxicillin:

• Any antibiotic—including azithromycin or amoxicillin—may cause a type of diarrhea called C. difficile-associated diarrhea. This type of diarrhea can be mild to life-threatening and can cause death if not treated. C. difficile-associated diarrhea can cause severe, watery, or bloody diarrhea and stomach cramps. If you have these symptoms, which can occur up to several months after you stop taking the antibiotic, get emergency medical help right away. 
• Azithromycin or amoxicillin should only be used to treat a bacterial infection. Using an antibiotic when there is not a bacterial infection (such as the flu, COVID-19, or the common cold, which are viral infections) will not benefit the patient and can lead to resistance.

Frequently asked questions about azithromycin vs. amoxicillin

What is azithromycin?

Azithromycin is a macrolide antibiotic that is used in the treatment of many different bacterial infections in adults and children. A common prescription is for the Zithromax Z-Pak. Other macrolide antibiotics you may have heard of include erythromycin and Biaxin (clarithromycin).

What is amoxicillin?

Amoxicillin is a beta-lactam antibiotic, related to penicillin, which is used to treat a variety of bacterial infections in adults and children. Amoxicillin is a very common prescription, and Augmentin (which contains amoxicillin plus clavulanate to prevent resistance) is another very common medication prescribed for various bacterial infections.

Are azithromycin and amoxicillin the same?

Both medications are used to treat bacterial infections in adults and children. Azithromycin is in the macrolide category of antibiotics, while amoxicillin is in the beta-lactam/penicillin category. They work in different ways and have some differences, such as in indications and drug interactions.

Can I take amoxicillin with azithromycin?

In most cases, only one or the other antibiotic will be prescribed. Always follow your healthcare provider’s instructions on what antibiotic to take. In some cases, such as pneumonia or another type of illness where the type of bacteria is not yet known, the healthcare provider may prescribe two antibiotics until lab work comes back that shows which antibiotic will work. 

Is azithromycin or amoxicillin better?

While both drugs are effective, your healthcare provider can determine if you do indeed have a bacterial infection. A viral infection does not respond to antibiotics and can increase drug resistance. Based on the type of infection, and what particular bacteria is suspected or known to be causing the infection, your healthcare provider can decide if one of these drugs is appropriate for you.

Can I use azithromycin or amoxicillin while pregnant?

Your healthcare provider will determine the best antibiotic to use if you are pregnant and need an antibiotic. 

Azithromycin is a pregnancy category B, but there have not been well-controlled studies in pregnant women. 

Amoxicillin is also a pregnancy category B, and like azithromycin, there have not been adequate studies with pregnant women. 

Therefore, azithromycin or amoxicillin should be prescribed if the benefits to the mother outweigh the risks to the baby, and under close observation of the healthcare provider. If you are pregnant or planning to become pregnant, tell your healthcare provider.

Can I use azithromycin or amoxicillin while breastfeeding?

The prescribing information for azithromycin recommends considering the risks versus benefits, and if it is used in a breastfeeding woman, the baby should be monitored for diarrhea, vomiting, or rash. 

The prescribing information for amoxicillin recommends that the medication should be used with caution in breastfeeding mothers. 

Women who are breastfeeding should consult their provider regarding the most appropriate antibiotic that will be safe during breastfeeding.

Can I use azithromycin or amoxicillin with alcohol?

While the manufacturer’s information does not list alcohol as a contraindication to or drug interaction with either antibiotic, it’s important to take note that alcohol can prevent your body from fighting an infection. Alcohol can also make gastrointestinal (stomach) side effects worse.

Azithromycin vs amoxicillin: Which is stronger?

It’s difficult to compare strengths because each medication is in a different category of antibiotics. They have some similarities and some differences, but we can’t really say which is stronger. Instead, it is important to look at what infection is being treated, what bacteria is causing the infection, any other medical conditions you have, and any drugs you take that can interact with azithromycin or amoxicillin. Your healthcare provider can determine which drug is more appropriate for you.

Amoxicillin vs azithromycin for COVID: Which is better? 

Amoxicillin and azithromycin are antibiotics and do not treat viral infections such as COVID-19. You can read more about COVID-19 treatments on the CDC website. It is important to stay up to date on your COVID-19 vaccines to help prevent serious illness or hospitalization. 

Which is better for sinus infection, amoxicillin, or azithromycin?

A sinus infection may be caused by a virus or by bacteria (or even a fungus, in rare cases). If your prescriber diagnoses you with a bacterial sinus infection, azithromycin or amoxicillin (or Augmentin) are appropriate and very common treatments. Your prescriber will also take into account allergies and other drugs you take that may interact with azithromycin or amoxicillin.

Which antibiotic is best for cough?

It depends if your cough is coming from a bacterial or viral infection. If you have a viral infection like the common cold, an antibiotic will not help at all. If your healthcare provider feels that a bacterial infection is causing the cough, they will choose the antibiotic that they believe is more likely to cure the particular infection.