Amoxicillin (Amoxil®) versus Clarithromycin (Biaxin®)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Amoxicillin advantages over Clarithromycin

  • Low potential for drug interactions.
  • Amoxicillin treatment course costs less than clarithromycin.

Clarithromycin advantages over Amoxicillin

  • Clarithromycin has a broader antimicrobial spectrum than amoxicillin.
  • More convenient twice-daily dosing schedule.
  • Safe for use in penicillin-allergic patients.

Difference between Amoxicillin and Clarithromycin


Table 1. Comparison of Amoxicillin and Clarithromycin

Amoxicillin Clarithromycin
Brand names
Amoxil® Biaxin®
Drug class
Penicillin antibiotic Macrolide antibiotic
Dose formulations
• Capsules
• Suspension
• Tablets
• Tablets, chewable
• Tablets, extended release
• Tablets
• Tablets, extended release
• Suspension
Antimicrobial spectrum
Gram-positive bacteria
• Enterococcus faecalis
• Staphylococcus spp.
• Streptococcus pneumoniae
• Alpha and beta-hemolytic streptococci.

Gram-negative bacteria

• Escherichia coli
• Haemophilus influenzae
• Neisseria gonorrhoeae
• Proteus mirabilis
• Helicobacter pylori

• Amoxicillin is not active against beta-lactamase producing bacteria.
Gram-positive bacteria
• Staphylococcus aureus
• Streptococcus pneumoniae
• Streptococcus pyogenes

Gram-negative bacteria
• Haemophilus influenzae
• Haemophilus parainfluenzae
• Moraxella catarrhalis

Other bacteria
• Mycoplasma pneumoniae
• Chlamydia pneumoniae
• Mycobacterium avium complex (MAC)

• Beta-lactamase production does not affect clarithromycin activity.
FDA-approved indications
Otitis media
• Sinusitis
Streptococcal pharyngitis
• Skin and skin structure infections
• Pneumonia
• In combination for treatment of H. pylori infection and duodenal ulcer disease.
• Acute bacterial exacerbation of chronic bronchitis
Otitis media
Streptococcal pharyngitis
• Community-acquired pneumonia
• Sinusitis
• Skin and skin structure infections
"Off-label" uses
• Anthrax, inhalational post-exposure prophylaxis
• Erysipeloid
• Infective endocarditis (prophylaxis)
• Lyme neuroborreliosis
Chlamydia infection in pregnant women
• Infective endocarditis (prophylaxis)
• Lyme disease
• Pertussis
Mechanism of action
• Inhibits the synthesis of bacterial cell walls by binding to penicillin-binding proteins.
• Inhibits bacterial protein synthesis via binding to 50S ribosomal subunit.
• Immediate-release: 61.3 minutes
• Extended-release: 90 minutes
• Clarithromycin: 3-7 hours
• 14-OH-clarithromycin metabolite: 5-9 hours
Oral bioavailability
• 74-92% • 50%
Metabolism, Elimination
• Amoxicillin is eliminated
in urine (60% as unchanged drug).
• Clarithromycin undergoes hepatic metabolism via CYP3A4. The drug is converted to 14-OH clarithromycin, an active metabolite.
• Clarithromycin is eliminated primarily via kidneys in urine (20-40% as unchanged drug; 10-15% as metabolite) and feces (29% to 40% mostly as metabolites).
• Hypersensitivity to penicillins, cephalosporins
• Hypersensitivity to macrolides
• Coadministration with pimozide, cisapride, ergotamine, and dihydroergotamine
• History of hepatic dysfunction associated with previous use of clarithromycin
• Coadministration with colchicine in patients with renal or hepatic impairment
Side effects
• Diarrhea
• Nausea
• Vomiting
• Rash
• Stomach pain
• Serious allergic reactions (anaphylaxis, serum sickness-like reaction)
• Abnormal taste
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Dyspepsia
• Heartburn
Drug interactions
• Low risk for drug interactions • Significant drug interactions potential


Head-to-head comparative studies


Clarithromycin and amoxicillin appear to have comparable effectiveness in the treatment of sinusitis1.

Results of comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis1. Amoxicillin Clarithromycin
Regimen 500 mg 3 times daily for 7 to 14 days 500 mg 2 times daily for 7 to 14 days
Clinical success rate (based on direct observation of the patient) 89% 91%
Roentgenographic success rate 92% 78%
Dropout rates 4% 3%
Adverse effects mild gastrointestinal side effects


Amoxicillin and clarithromycin are equally effective in the treatment of community-acquired pneumonia in children.

In a randomized clinical trial3 the mean hospital stay in patients treated with amoxicillin was 3.3 days and with clarithromycin was 3.2 days. About 97% patients in both treatment groups achieved symptoms improvement.

Otitis media

Clarithromycin and amoxicillin are similarly effective in the treatment of acute ear infection (otitis media).

Results of single blind, randomized, multicenter clinical trial2 comparing the safety and efficacy of clarithromycin and amoxicillin Amoxicillin suspension Clarithromycin suspension
Clinical success (cure and symptoms improvement) rates at 0 to 4 days posttreatment 90% 93%

Erythema migrans (the rash characteristic of Lyme disease)

Clarithromycin works a little better than amoxicillin in the treatment of children with solitary erythema migrans.

Results of comparative study4 of children with solitary erythema migrans Amoxicillin Clarithromycin
Average duration of erythema migrans after starting the antibiotic 4 days
Duration of Lyme borreliosis symptoms 10 day 7 days
Minor manifestations of Lyme borreliosis 16 of 54 patients
11 of 50 patients
Major manifestations of Lyme borreliosis 2 patients
Not detected
Side effects 28.1% 24.2%

Further reading


  • 1. Calhoun KH, Hokanson JA. Multicenter comparison of clarithromycin and amoxicillin in the treatment of acute maxillary sinusitis. Arch Fam Med. 1993 Aug;2(8):837-40. PubMed
  • 2. Pukander JS, Jero JP, Kaprio EA, Sorri MJ. Clarithromycin vs. amoxicillin suspensions in the treatment of pediatric patients with acute otitis media. Pediatr Infect Dis J. 1993 Dec;12(12 Suppl 3):S118-21. PubMed
  • 3. Aurangzeb B, Hameed A. Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community-acquired pneumonia in children. J Coll Physicians Surg Pak. 2003 Dec;13(12):704-7. PubMed
  • 4. Nizic T, Velikanje E, Ruzic-Sabljic E, Arnez M. Solitary erythema migrans in children: comparison of treatment with clarithromycin and amoxicillin. Wien Klin Wochenschr. 2012 Jul

Published: October 25, 2017
Last updated: October 25, 2017


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