Azithromycin vs. Amoxicillin: Differences and Similarities

Azithromycin and amoxicillin are broad spectrum antibiotics that belong to two different drug classes and are used to treat slightly different types of infections. 

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Most people have taken an antibiotic at some point in their lives as a result of a common bacterial infection, like acute sinusitis, bronchitis, or an ear infection.

Two of the most common medications for the treatment of bacterial infections include azithromycin and amoxicillin, both of which are broad spectrum antibiotics. 

When it comes to azithromycin vs. amoxicillin, what are the significant differences and similarities?

Azithromycin vs. Amoxicillin: Overview

Azithromycin and amoxicillin are two commonly used antibiotics that are used to treat a variety of bacterial infections.

Nearly everyone has had antibiotic therapy at some point in their lives, and amoxicillin and azithromycin are two of the most popular.

Azithromycin is the generic form of the brand-name drug Zithromax, which is well known as the Zithromax Z-Pak. Azithromycin belongs to a class of drugs called macrolide antibiotics, which work by stopping the bacteria from producing certain proteins that are required for reproduction and survival. 

Amoxicillin is the generic form of the brand-name drug Amoxil.

The drug belongs to a class of medications called penicillin or beta-lactam antibiotics, which work differently from macrolide antibiotics.

Penicillin antibiotics, like amoxicillin, stop harmful bacteria from building or maintaining their cell wall, which kills the bacteria. 

Azithromycin vs. Amoxicillin: Conditions Treated

Azithromycin and amoxicillin are both used to treat bacterial infections in children and adults, but their applications are slightly different. 

The most common applications of azithromycin include:

  • Acute bacterial exacerbations of chronic bronchitis caused by bacteria that include Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
  • Community-acquired pneumonia in patients ages six months and older caused by bacteria including Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, or Streptococcus pneumoniae 
  • Uncomplicated skin/skin structure infections caused by bacteria including Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae
  • Genital ulcer disease in men caused by Haemophilus ducreyi (chancroid)
  • Acute bacterial sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae
  • Pharyngitis/tonsillitis caused by Streptococcus pyogenes in patients who cannot use first-line therapy treatments and are over the age of two. 
  • Urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae
  • 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, including:

  • Ear/nose/throat infections caused by bacteria including Streptococcus, pneumoniae, Staphylococcus spp., or H. influenzae
  • Skin/skin structure infections caused by certain strains of Streptococcus, Staphylococcus, or E. coli
  • Acute uncomplicated gonorrhea in males and females caused by gonorrhoeae
  • H. Pylori infections when used along with lansoprazole and clarithromycin
  • Genitourinary tract infections caused by E. coli, P. mirabilis, or E. faecalis
  • Lower respiratory tract infections due to certain strains of Streptococcus, S. pneumoniae, Staphylococcus, or H. influenzae

While both azithromycin and amoxicillin are used to treat bacterial infections, each drug works in different ways and may have different uses. 

Azithromycin vs. Amoxicillin: Available Forms

Both azithromycin and amoxicillin are available in different formulations. Azithromycin is available in the form of a tablet, suspension, injection, powder packet, or eye drop.

Most people use azithromycin as part of a Z-pak, which comes in the form of tablets that are taken over the course of five days. 

Amoxicillin is available in many different forms, including a capsule, tablet, suspension, and chewable tablet. 

Standard Dosage and Length of Treatment

Bacterial infections take a number of days to resolve, so one of the most important elements of antibiotic treatment is taking the prescribed dose every day until the treatment is finished. 

Often, patients will take their antibiotic until they start feeling better and then stop taking the medication, even when they still have medication left in their prescription.

This contributes to antibiotic resistance, as harmful bacteria learn to adapt to the antibiotic, making them more harmful in the future. 

Azithromycin is most commonly prescribed in the form of a Z-pak. Patients who are prescribed a Z-pak will take two tablets on day 1 of treatment, then one tablet each day for days 2 through 5.

When used outside of a Z-pak, the length of treatment varies depending on the condition being treated.

Most adults will take a daily dose of azithromycin that is between 500 and 2000 mg in strength over the course of several days. Amoxicillin doses vary depending on the infection being treated. Amoxicillin is most commonly prescribed at a dose of 500 mg taken three times per day over the course of ten days.

Most adults will take a dose of amoxicillin that is between 250 mg and 875 mg, depending on how often the dose is taken. 

Azithromycin vs. Amoxicillin: Side Effects

The side effects caused by azithromycin and amoxicillin may be slightly different. 
Common side effects associated with azithromycin include:

  • Diarrhea or loose stools
  • Abdominal pain
  • Nausea
  • Vomiting

Less common side effects of azithromycin include:

  • Rash
  • Vaginitis
  • Ringing in the ears
  • Nervousness
  • Tongue discoloration
  • Indigestion

Rare but serious and sometimes life-threatening side effects of azithromycin include:

  • Angioedema
  • Cholestatic jaundice
  • Serious allergic reactions
  • Abnormal liver tests
  • Steven-Johnson Syndrome
  • Abnormal heart beats

Common side effects that are attributed to the use of amoxicillin include:  

  • Diarrhea
  • Nausea
  • Itching
  • Vomiting
  • Dizziness
  • Heartburn
  • Insomnia
  • Abdominal pain
  • Easy bruising
  • Bleeding
  • Confusion
  • Rash
  • Allergic reactions

Serious but rare and possibly life-threatening reactions associated with amoxicillin include:

  • Seizures
  • Low platelet levels (thrombocytopenia)
  • Severe allergic reactions (anaphylaxis).

If you experience an allergic reaction, seek medical attention immediately.

Contact your healthcare provider if you experience side effects, or they persist or worsen.

If symptoms of your infection continue, you may need to seek treatment follow-up in case of treatment failure with the antibiotic. The prevalence of each side effect will vary.

Antibiotics like azithromycin and amoxicillin can disrupt the normal balance of bacteria in the colon by eliminating good bacteria in addition to harmful bacteria.

Some bacteria, such as Clostridium difficile can be affected by the use of antibiotics.

Patients who begin to experience colon inflammation (pseudomembranous colitis) and severe diarrhea after starting treatment with azithromycin should contact a healthcare professional immediately. 

Azithromycin vs. Amoxicillin: Drug Interactions

Compared to other prescription drugs, amoxicillin and azithromycin are associated with a relatively low rate of drug interactions. 

Amoxicillin in particular is associated with few drug interactions, while azithromycin is known to interact with aluminum or magnesium-based antacids, including Maalox and Mylanta. 

These antacids have been found to prevent azithromycin from being absorbed by the intestine, making them less effective and potentially contributing to antibiotic resistance.

Azithromycin vs. Amoxicillin: Warnings

Azithromycin should not be used to treat pneumonia in patients who have any of the following medical conditions:

  • Cystic fibrosis
  • Nosocomial (hospital-acquired) infections
  • Known or suspected bacteremia (bacteria in the blood)

Additionally, azithromycin should not be used to treat patients who are elderly or disabled, immunocompromised, or hospitalized.

Azithromycin should also be avoided in people who have no spleen (asplenia). People who are allergic or have hypersensitivity to a class of antibiotics known as cephalosporin antibiotics, including cefaclor (Ceclor), cephalexin (Keflex), and cefprozil (Cefzil), should use caution when taking penicillin antibiotics like amoxicillin, as there may be an increased risk of an allergic reaction with the penicillin. 

Azithromycin vs. Amoxicillin: Cost

Azithromycin and amoxicillin are both sold primarily as generic drugs. No brand-name form of amoxicillin is available on the market today.

Azithromycin and amoxicillin are both low-cost medications that are covered by nearly all health insurance plans and are available for less than 20 dollars without insurance. 

Pharmacy discount cards can provide savings for patients using azithromycin or amoxicillin to treat bacterial infections regardless of their insured status.

Effectiveness

The effectiveness of azithromycin or amoxicillin will vary depending on the condition being treated. Due to the abundant use of both antibiotics in the treatment of many different bacterial infections, there is a risk of antibiotic resistance, which can make them less effective against certain types of infections. 

When it comes to the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD), both azithromycin and  amoxicillin have been found to be similarly effective.

Azithromycin is also similarly effective to amoxicillin in lower doses for the treatment of acute sinusitis caused by bacterial infection. 

Summary

Azithromycin and amoxicillin are popular broad-spectrum antibiotics that are used for the treatment of a number of different bacterial infections. 

While both antibiotics are safe and effective for bacterial infections, a healthcare provider should be consulted on the best antibiotic for your specific condition. 

Both medications are widely available in their generic forms and are covered by the vast majority of commercial insurance plans. 

Patients who do not have access to commercial insurance can save money on the cost of their prescription by using a pharmacy discount card from Pharmacists.org.

References, Studies, and Sources:

https://www.medicinenet.com/amoxicillin_moxatag_vs_azithromycin_zithromax/article.htm#what_are_the_side_effects_of_amoxicillin_and_azithromycin 
https://www.healthline.com/health/strep-throat/z-pack 
https://pubmed.ncbi.nlm.nih.gov/17568867/ 
https://pubmed.ncbi.nlm.nih.gov/9950107/

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