Azithromycin vs. Amoxicillin: What’s the Difference?

Azithromycin and amoxicillin are commonly prescribed antibiotics used to treat various bacterial infections, such as pneumonia, bronchitis, or urinary tract infections (UTIs). While similar, they are classified as different types of antibiotics, with different uses, side effects, and drug interactions.

What Is Azithromycin?

Azithromycin is a macrolide antibiotic that stops bacterial infections from spreading in the body. It’s often known by its brand name, Zithromax, or Zithromax Z-Pak.

FDA-Approved Uses

Azithromycin is approved by the Food and Drug Administration (FDA) to treat certain bacterial infections, including:

• Bronchitis
• Pneumonia
• Certain sexually transmitted infections (STIs)
• Certain infections involving the lungs, ears, throat, sinuses, skin, and reproductive organs

It can also be used to treat or prevent a type of lung infection associated with human immunodeficiency virus (HIV) called Mycobacterium avium complex (MAC) infection.

Off-Label Uses

Sometimes, healthcare providers may prescribe azithromycin off-label for infants who are younger than indicated (approved by the FDA). Or, they may prescribe higher doses of azithromycin than are FDA-approved.

In both cases, these would be examples of off-label uses. Off-label prescribing occurs when a medication is used in a way or for a purpose for which it was not originally FDA-approved.

Other examples of off-label azithromycin use include but are not limited to:

• Treatment of trachoma (a bacterial eye infection)
• Maintenance treatment in people who frequently have worsening of chronic obstructive pulmonary disease (COPD), which includes lung diseases such as emphysema and chronic bronchitis that make breathing difficult

Forms of Administration

Azithromycin can be taken in several forms, such as:

• Oral tablets
• Oral suspension (liquid)
• Single-dose suspension
• Injection
• Eye drops (sold as Azasite)

What Is Amoxicillin?

Amoxicillin is a penicillin-type antibiotic that prevents bacteria from growing. It’s sometimes known by its brand name, Amoxil, though it’s often available as a generic.

FDA-Approved Uses

The FDA has approved amoxicillin to treat certain bacterial infections, including:

• Pneumonia
• Bronchitis
• Infections of the ears, nose, throat, urinary tract, and skin

Amoxicillin is also prescribed along with other medications to treat Helicobacter pylori (H. pylori), a bacteria that causes ulcers (sores on the lining of the esophagus, stomach, or small intestine).

Off-Label Uses

Some examples of off-label amoxicillin use include but are not limited to:

• Treatment for actinomycosis (a long-term bacterial infection affecting the lungs in 15% of cases, but often involving the face and neck)
• Treat bacterial bone and joint infections

Forms of Administration

Amoxicillin is available in various dosage forms, including:

• Oral tablets
• Oral chewable tablets
• Oral capsules
• Oral suspension (liquid)

Azithromycin Dosing Guidelines

Azithromycin can be given to adults and children, with dosing in children based on the infection type and the child’s weight. Always use a medicinal measuring device when measuring the liquid medication.

For adults, the dose depends on the type of infection:

• A standard dosage for many infections is the Z-Pak: 500 milligrams (mg) by mouth on the first usage dose, from there, 250 mg once daily on days two through five.
• For sinus infections or certain other types, a typical dose is 500 mg orally daily for three days.
• For the sexually transmitted infection chancroid, or for nongonococcal (not caused by gonorrhea bacteria) urethritis, an inflammation of the tube that carries urine from the bladder to outside the body, healthcare providers prescribe a single 1-gram dose. That’ also true for cervicitis, an inflammation of the cervix connecting the uterus and vagina.
• For gonococcal (caused by gonorrhea bacteria) urethritis and cervicitis, healthcare providers prescribe a 2-gram dosage.

Azithromycin can be taken with or without food.

Amoxicillin Dosing Guidelines

Amoxicillin can be given to adults and children. Dosing in children depends on infection type and the child’s weight. Always use a medicinal measuring device, such as a medicine spoon or cup, when measuring the liquid suspension form of administration.

For adults, the dose depends on the type of infection, as follows:

• For mild to moderate ear, nose, throat, skin, or genitourinary tract infections (diseases of the genital and urinary organs), typical doses are 500 mg by mouth every 12 hours or 250 mg by mouth every eight hours.
• For severe ear, nose, throat, skin, or genitourinary tract infections, typical doses are 875 mg by mouth every 12 hours or 500 mg by mouth every eight hours.
• For severe lower respiratory tract infections (such as pneumonia or bronchitis), typical doses are 875 mg by mouth every 12 hours or 500 mg by mouth every eight hours.

Your healthcare provider will determine the length of treatment by the type and severity of infection. It is usually anywhere from five to 14 days but could be longer in some cases.

Amoxicillin can be taken with or without food.

Which Is More Effective?

Studies have found azithromycin and amoxicillin are among the most frequently used antibiotics in the world for treating respiratory illness. They are both effective and well-tolerated, though a 2021 review of 14 studies found that of the two, azithromycin may be safer and better tolerated in children with ear infections.

Because both drugs are considered safe and effective, and because there are many factors to consider when selecting the most appropriate antibiotic, your healthcare provider will decide which antibiotic is best for your bacterial infection.

Azithromycin Side Effects

Common side effects of azithromycin may include:

Severe side effects of azithromycin may include:

• Symptoms of jaundice, such as yellowing of the skin or whites of the eyes
• Upper stomach pain
• Flu-like symptoms
• Muscle weakness
• Lethargy
• Unusual bleeding or bruising
• Appetite loss
• Pink and swollen eyes
• Vomiting or irritability while feeding in infants less than 6 weeks old

Amoxicillin Side Effects

Common side effects of amoxicillin may include:

• Nausea
• Vomiting
• Diarrhea
• Altered taste
• Headache

Severe side effects of amoxicillin may include:

• Rash
• Skin blisters or peeling
• Itching
• Hives
• Wheezing

Potential for Interaction

Before taking an antibiotic, ensure your healthcare provider knows if you are allergic to any medications.

Also, make sure your provider knows about all the medications you take, including:

• Prescription medications
• Over-the-counter (OTC) medicines
• Vitamins
• Supplements

Azithromycin-Specific Interactions

Examples of medications that may interact with azithromycin include:

• Blood-thinning medications, such as Jantoven (warfarin)
• Anti-inflammatory medications used for gout, such as Mitigare (colchicine)
• Immunosuppressive drugs used to treat organ rejection post-transplant, such as Sandimmune (cyclosporine)
• Drugs used for the treatment of heart failure (HF), such as Lanoxin (digoxin)
• Drugs used to treat and prevent seizures, such as Dilantin (phenytoin)
• Drugs used to treat heart rhythm problems, such as Pacerone (amiodarone)
• Drugs used for the treatment of multiple sclerosis (MS), such as generic quinidine
• Drugs used to treat human immunodeficiency virus (HIV), such as Viracept (nelfinavir)
• Antacids that contain aluminum or magnesium hydroxide, such as Tums (if taking with azithromycin, doses of each should be spaced at least two hours apart, but consult with your prescribing provider or pharmacist on proper scheduling)

Amoxicillin-Specific Interactions

Examples of medications that may interact with amoxicillin include:

• Other anti-inflammatory medications, such as Probalan (probenecid) or Aloprim (allopurinol)
• Jantoven (warfarin)