Orris

Amoxicillin

Reading File
Finding Sources
Finding Sources
Reading File
Reading File
Reading File
I now have excellent content from multiple authoritative sources. Let me compile the comprehensive answer:

Amoxicillin

Drug Class & Structure

Amoxicillin is an aminopenicillin (extended-spectrum penicillin), a beta-lactam antibiotic. It is a close structural relative of ampicillin, differing by a hydroxyl group on the benzyl side chain. Like all penicillins, it contains a beta-lactam ring that is the pharmacophore for antibacterial activity.
  • Katzung's Basic and Clinical Pharmacology, 16th Ed., p. 1245

Mechanism of Action

Amoxicillin works by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) on the inner membrane of the bacterial cell wall, blocking transpeptidation (cross-linking of peptidoglycan chains). This leads to activation of autolytic enzymes and bacterial cell lysis. It is bactericidal.

Spectrum of Activity

Amoxicillin is broadly bactericidal against susceptible gram-positive and gram-negative bacteria:
Gram-positive coverage:
  • Streptococcus pyogenes, S. pneumoniae (variable - see high-dose dosing for resistant strains)
  • Viridans group streptococci
  • Enterococci (approximately twice as sensitive as to penicillin G)
  • Listeria monocytogenes
Gram-negative coverage:
  • H. influenzae (strains not producing beta-lactamase; ~60-80% of isolates)
  • E. coli (30-60% resistant due to beta-lactamases)
  • Proteus mirabilis (some resistance)
  • Salmonella sp. (though resistant strains increasingly common)
Not active against:
  • Beta-lactamase-producing Staphylococcus aureus
  • Klebsiella sp., Enterobacter sp., Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter, indole-positive Proteus, B. fragilis
  • Methicillin-resistant Staphylococcus aureus (MRSA)
  • Shigella (amoxicillin is less effective than ampicillin for shigellosis)
  • Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 750-754

Pharmacokinetics (ADME)

ParameterDetail
AbsorptionExcellent oral bioavailability; food does NOT interfere with absorption (unlike ampicillin)
Peak plasma levels2-2.5x greater than equivalent oral dose of ampicillin
DistributionWidely distributed; penetrates most tissues and body fluids
Half-life~80 min (similar to ampicillin), but effective plasma concentrations last twice as long due to more complete absorption
MetabolismMinimal hepatic metabolism
EliminationPrimarily renal excretion; dose adjustment required in renal impairment
Key advantage over ampicillin: Because it is better absorbed, the incidence of diarrhea (from unabsorbed drug affecting gut flora) is lower. This is why amoxicillin is generally preferred over ampicillin for oral use.
  • Goodman & Gilman's, p. 760

Formulations

  • Oral suspension: 125, 250 mg/5 mL and 200, 400 mg/5 mL
  • Capsules: 250, 500 mg
  • Tablets: 500, 875 mg
  • Chewable tablets: 125, 250 mg (may contain phenylalanine - caution in phenylketonuria)

Dosing

Adults

IndicationDose
Mild/moderate infections250 mg Q8h PO or 500 mg Q12h PO
Severe infections500 mg Q8h PO or 875 mg Q12h PO
Max daily dose2-3 g/24h
SBE prophylaxis (pre-procedure)2 g PO x 1 (30-60 min before)
Early Lyme disease500 mg Q8h x 14-21 days

Pediatric

Age/IndicationDose
Neonate/≤3 mo20-30 mg/kg/24h Q12h PO
Child (standard)25-50 mg/kg/24h Q8-12h PO
Child (high-dose, resistant S. pneumoniae)80-90 mg/kg/24h Q8-12h PO; max 2-4 g/24h
Tonsillitis/pharyngitis (S. pyogenes)50 mg/kg/24h Q12h x 10 days; max 1 g/24h
SBE prophylaxis50 mg/kg PO x 1; max 2 g/dose
Early Lyme disease50 mg/kg/24h Q8h x 14-21 days; max 1.5 g/24h
  • The Harriet Lane Handbook, 23rd Ed., p. 1014

Clinical Indications

  • Otitis media (AOM) - first-line per AAP 2013 guidelines; dose 80-90 mg/kg/day in two divided doses
  • Upper and lower respiratory tract infections (community-acquired pneumonia - mild/moderate)
  • Streptococcal pharyngitis/tonsillitis
  • Urinary tract infections (susceptible organisms only)
  • Skin and soft tissue infections (susceptible streptococcal/staphylococcal)
  • Lyme disease (early, localized or disseminated)
  • H. pylori eradication (as part of PPI-based triple therapy, e.g., PPI + amoxicillin + clarithromycin or metronidazole)
  • SBE prophylaxis (dental/invasive procedures)
  • Sinusitis
  • Cummings Otolaryngology, Head and Neck Surgery

Adverse Effects

  • Rash - most common; maculopapular rash is NOT a true allergy. A florid rash occurs in nearly 100% of patients with EBV (mononucleosis) given amoxicillin - this is NOT a penicillin allergy.
  • Diarrhea (less than ampicillin due to better absorption)
  • Hypersensitivity / anaphylaxis - true IgE-mediated allergy (rare but serious)
  • C. difficile-associated diarrhea/colitis
  • Drug interactions: may increase warfarin's anticoagulant effect (monitor INR)

Beta-Lactamase Susceptibility & Combination

Amoxicillin is hydrolyzed and inactivated by beta-lactamases produced by many gram-positive and gram-negative bacteria. To overcome this, it is co-formulated with clavulanate (a beta-lactamase inhibitor) as:
  • Amoxicillin-clavulanate (Augmentin) - extends coverage to S. aureus (MSSA), H. influenzae, E. coli, Klebsiella, Proteus, B. fragilis
Common formulation ratios: 7:1 and 14:1 (amoxicillin:clavulanate), e.g., Augmentin ES-600 (600 mg amoxicillin/5 mL).

Renal Dosing

Dose adjustment is required in renal failure. Serum levels with amoxicillin are about twice those achieved with an equal dose of ampicillin, so monitoring is especially important in renal impairment.
Sources: Katzung's Basic and Clinical Pharmacology 16th Ed. | Goodman & Gilman's Pharmacological Basis of Therapeutics | The Harriet Lane Handbook 23rd Ed. (Johns Hopkins) | Cummings Otolaryngology | Goodman & Gilman's
This is a shared conversation. Sign in to Orris to start your own chat.