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Drug vs. Drug

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

Karen Berger medical writer and reviewer headshot By | Updated on June 30, 2020

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

If you have ever suffered from a bacterial sinus infection or a variety of other types of bacterial infections, chances are you have taken an antibiotic. Azithromycin and amoxicillin are two of the most common antibiotics used in the treatment of bacterial infections. Antibiotics are used in the treatment of bacterial infections, and will not work for viral infections such as the flu or common cold.

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 of 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.

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 of 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 in combination with clavulanic acid (to prevent resistance) as Augmentin. Amoxicillin is commonly used in adults and children, and the dosage varies by indication.

It’s important to note that when you are prescribed an antibiotic, you should take it as directed, and finish the full course, even if you are feeling better. However, if you have been taking an antibiotic for several days and you 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 Brand and generic
What is the brand name? Zithromax Amoxil, Trimox (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 on day 1, then 1 tablet daily on days 2 through 5 500 mg 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 patients with pneumonia who have cystic fibrosis, nosocomial (hospital-acquired) infections, known or suspected bacteremia (bacteria in the blood), hospitalized patients, elderly or debilitated patients, or patients with a compromised immune system or asplenia (no spleen).

  • Acute bacterial exacerbations of chronic bronchitis from Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
  • Acute bacterial 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 (otitis media) (>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
  • Genitourinary tract infections from coli, P. mirabilis, or E. faecalis
  • Skin/skin structure infections caused by certain strains of StreptococcusStaphylococcus, or E. coli
  • 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 gonorrhoeae
  • Eradication of 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 pylori infection and duodenal ulcer

To reduce the development of antimicrobial resistance, azithromycin or amoxicillin should only be used in bacterial infections when determined to be appropriate by your healthcare provider. 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.

One study compared a single dose of azithromycin to a 10-day regimen of amoxicillin-clavulanate (Augmentin) for children with ear infections. The researchers found both drugs to be effective and well-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.

If you think you have a bacterial infection, see your healthcare provider as soon as possible. He or she can examine and assess you, and determine the need for antibiotics, and 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 Part D. A typical prescription would be for a generic Z-Pak, and the out-of-pocket cost would be about $33. With SingleCare, the price starts less than $10 at participating pharmacies.

Amoxicillin is also usually covered by insurance plans and Medicare Part D. A typical prescription would be for 30 capsules of amoxicillin 500 mg, and the out-of-pocket price would be approximately $16. It’s around $5 with a SingleCare coupon.

  Azithromycin Amoxicillin
Typically covered by insurance? Yes Yes
Typically covered by Medicare Part D? Yes Yes
Standard dosage 1 Z-Pak (#6, 250 mg tablets) #30, 500 mg capsules
Typical Medicare Part D copay $0-$3 $0-$1
SingleCare cost $8 $5

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 treatment, 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 azithromycin in combination with an anticoagulant such as warfarin may affect bleeding; patients should be monitored. Drug interactions may 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.

Taking amoxicillin with an anticoagulant like warfarin may affect bleeding; patients should be monitored. Allopurinol in combination with amoxicillin can lead to a greater incidence of rash.

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

This is not a complete list of drug interactions. Other drug interactions may occur. Consult your healthcare provider for 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
Other 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.
  • You should not take azithromycin if you have a history of liver problems from prior use of azithromycin.
  • Serious allergic reactions (including angioedema, anaphylaxis, Acute Generalized Exanthematous Pustulosis, Stevens-Johnson syndrome, and/or toxic epidermal necrolysis) may occur. Fatalities have been reported. If an allergic reaction occurs, you should stop the drug immediately and seek emergency treatment.
  • 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.
  • Infantile Hypertrophic Pyloric Stenosis has been reported in neonates (<42 days old). Contact your physician if your neonate 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, elderly patients, and patients with uncorrected low potassium or magnesium.
  • Azithromycin may exacerbate symptoms of myasthenia gravis or may be associated with a new onset.
  • 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 penicillins.
  • Serious, occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported. This can occur in patients who are being treated with cephalosporins (such as 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:

  • Clostridium difficile-associated diarrhea has been reported with most antibiotics and may range in severity from mild diarrhea to fatal colitis. It may occur during or after antibiotic use, even several months later. Contact your healthcare provider immediately if you experience diarrhea, nausea, abdominal pain, and/or fever.
  • 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 or 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.

Is azithromycin or amoxicillin better?

While both drugs are effective, it is best to see your healthcare provider who 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 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 benefits to the mother outweigh risks to the baby, and under close observation of the healthcare provider.

Can I use azithromycin or amoxicillin with alcohol?

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

Is azithromycin stronger than amoxicillin?

It’s difficult to compare strength 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, and 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.

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, he or she will choose the antibiotic that he/she feels is more likely to cure the particular infection.