Amoxicillin vs. Azithromycin

See how Amoxicillin and Azithromycin compare on approved uses, dosing, side effects, and cost.

Key Takeaways

  • Amoxicillin is a penicillin-class antibiotic usually dosed two to three times a day for 7 to 10 days, while azithromycin is a macrolide often finished in just 3 to 5 days.

  • Azithromycin causes nausea and diarrhea more often than amoxicillin, but amoxicillin carries a higher risk of allergic rash and anaphylaxis in penicillin-sensitive patients.

  • Both cover many respiratory, skin, and ear infections, but azithromycin also treats chlamydia and other atypical bacteria that amoxicillin does not reach.

Amoxicillin vs. Azithromycin Drug Summary

Amoxicillin

Amoxicillin is an aminopenicillin antibiotic used to treat ear, sinus, throat, urinary, and skin infections caused by susceptible bacteria. It comes as a capsule, tablet, chewable, or liquid, usually taken two to three times a day for 7 to 10 days.

Azithromycin

Azithromycin is a macrolide antibiotic used for respiratory infections, skin infections, and sexually transmitted infections like chlamydia. It's usually taken as a tablet or liquid once daily for 3 to 5 days, or as a single dose for certain infections.

Amoxicillin vs. Azithromycin Side Effects

Amoxicillin

Most common
vomiting (greater than 1%)
nausea (greater than 1%)
diarrhea (greater than 1%)
rash (greater than 1%)

Azithromycin

Most common
vomiting (up to 7%)
nausea (up to 18%)
loose stools (up to 14%)
abdominal pain (up to 7%)

Amoxicillin vs. Azithromycin Dosage

Amoxicillin

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 1 g three times daily At the start
Maximum dose 1 g three times daily Same as starting
Dose changes None Fixed dose

Azithromycin

Dosage
Dosage Table
STAGE DOSE WHEN
Starting dose 500 mg once Day 1
Maximum dose 5 mg/kg once daily Days 2-5
Dose changes 4 increases As tolerated

Amoxicillin vs. Azithromycin Indications

Amoxicillin

Amoxicillin treats a wide range of common bacterial infections, including ear, throat, sinus, urinary tract, and skin infections. It's also combined with other medications to eradicate H. pylori, the bacteria linked to stomach ulcers. It has no effect on viral illnesses like colds or the flu.

  • Ear, nose, and throat infections

  • Lower respiratory tract infections

  • Skin and skin structure infections

  • Urinary tract infections

  • H. pylori eradication (combination therapy)

Azithromycin

Azithromycin treats respiratory infections such as pneumonia, bronchitis, and sinusitis, along with skin infections and several sexually transmitted infections. It's also FDA-approved for pelvic inflammatory disease and ear infections in children. It is sometimes used off-label for traveler's diarrhea.

  • Community-acquired pneumonia

  • Acute bacterial sinusitis and bronchitis

  • Skin and skin structure infections

  • Chlamydia, urethritis, and cervicitis

  • Pelvic inflammatory disease

Amoxicillin vs. Azithromycin Pros and Cons

Amoxicillin

Amoxicillin has decades of established safety data and remains one of the most affordable, widely stocked antibiotics available. Its main drawback is a multiple-times-daily dosing schedule that some patients find harder to stick with over a full course.

Pros

  • Decades of established safety data

  • Roughly $11 to $25 per month, one of the least costly antibiotics

  • Lower risk of drug interactions than azithromycin

  • Considered safe as a first-line option in pregnancy

Cons

  • Requires dosing 2 to 3 times daily

  • Higher rash risk in penicillin-sensitive patients

  • Not effective against atypical bacteria like chlamydia

  • Cross-reactivity risk in patients with penicillin allergy

Azithromycin

Azithromycin's long tissue half-life allows short 3 to 5 day courses or even a single dose, which many patients find easier to complete. It carries a specific warning for QT prolongation and tends to cause more gastrointestinal side effects than amoxicillin.

Pros

  • Short 3 to 5 day or single-dose regimens

  • Once-daily dosing improves adherence

  • Covers atypical bacteria like chlamydia

  • Useful alternative for patients with penicillin allergy

Cons

  • Risk of QT prolongation and heart rhythm issues

  • Higher rates of nausea and diarrhea

  • Risk of serious liver toxicity

  • Brand Zithromax runs $150 to $400, well above generic amoxicillin

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