Introduction
Amoxicillin is a broad-spectrum aminopenicillin antibiotic belonging to the beta-lactam class. It is one of the most commonly prescribed antibiotics worldwide due to its effectiveness against a wide range of bacterial pathogens, favorable safety profile, and excellent oral bioavailability. First introduced in 1972, amoxicillin remains a first-line treatment for numerous common bacterial infections.
Mechanism of Action
Amoxicillin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) located inside the bacterial cell wall, disrupting the final transpeptidation step of peptidoglycan synthesis. This action causes weakening of the cell wall and ultimately leads to osmotic instability and cell lysis. Amoxicillin is particularly effective against actively dividing bacteria and exhibits time-dependent killing kinetics.
Indications
FDA-approved indications include:
- Acute bacterial otitis media (caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis)
- Streptococcal pharyngitis and tonsillitis
- Acute bacterial exacerbations of chronic bronchitis
- Community-acquired pneumonia
- Acute uncomplicated gonorrhea
- Skin and skin structure infections
- Urinary tract infections
- Helicobacter pylori eradication (in combination with other agents)
- Prophylaxis against bacterial endocarditis
Off-label uses include:
- Lyme disease prophylaxis
- Dental infection prophylaxis
- Anthrax exposure prophylaxis
Dosage and Administration
Standard adult dosing:- Mild to moderate infections: 250-500 mg every 8 hours
- Severe infections: 500-875 mg every 8 hours or 500 mg every 12 hours
- 20-50 mg/kg/day divided every 8 hours
- Otitis media: 80-90 mg/kg/day divided every 12 hours
- Renal impairment: Adjust dose based on creatinine clearance
- CrCl 10-30 mL/min: 250-500 mg every 12 hours - CrCl <10 mL/min: 250-500 mg every 24 hours
- Hepatic impairment: No specific dosage adjustment required
- Elderly: Consider renal function adjustments
- May be taken with or without food (food does not significantly affect absorption)
- Oral suspension should be shaken well before use
- Complete full course of therapy even if symptoms improve
Pharmacokinetics
Absorption: Well-absorbed from GI tract (74-92% bioavailability), not significantly affected by food Distribution: Widely distributed to most tissues and body fluids; crosses placenta and enters breast milk Protein binding: Approximately 20% Metabolism: Minimal hepatic metabolism (less than 30%) Elimination: Primarily renal excretion (50-70% unchanged in urine within 7 hours) Half-life: 1-1.5 hours (prolonged in renal impairment)Contraindications
- History of hypersensitivity to amoxicillin or other penicillins
- History of amoxicillin-associated cholestatic jaundice/hepatic dysfunction
- Patients with infectious mononucleosis (high incidence of rash)
Warnings and Precautions
- Hypersensitivity reactions: May range from mild rash to anaphylaxis
- Clostridium difficile-associated diarrhea: May occur during or after treatment
- Superinfections: Fungal or bacterial superinfections may occur
- Renal impairment: Requires dosage adjustment
- Mono nucleosis: High incidence of non-allergic rash
- Crystal luria: May occur with high doses, especially in dehydrated patients
- Pregnancy: Category B - generally considered safe but use only if clearly needed
- Breastfeeding: Compatible - low concentrations in breast milk
Drug Interactions
- Probenecid: Decreases renal tubular secretion of amoxicillin, increasing serum concentrations
- Oral contraceptives: May decrease efficacy of oral contraceptives
- Allopurinol: Increased incidence of skin rash
- Warfarin: May potentiate anticoagulant effect
- Methotrexate: May decrease methotrexate clearance
- Bacteriostatic antibiotics: May antagonize bactericidal effect
Adverse Effects
Common (≥1%):- Diarrhea (7%)
- Nausea (3%)
- Skin rash (3%)
- Vomiting (2%)
- Vaginal candidiasis
- Anaphylaxis
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Hepatitis
- Interstitial nephritis
- Blood dyscrasias (anemia, thrombocytopenia, neutropenia)
- Seizures (with high doses in renal impairment)
- Pseudomembranous colitis
Monitoring Parameters
- Clinical response to therapy
- Signs of hypersensitivity reactions
- Renal function (in patients with renal impairment)
- Hepatic function (with prolonged therapy)
- Complete blood count (with prolonged therapy)
- Signs of superinfection or C. difficile infection
- Serum electrolytes in patients receiving high doses
Patient Education
- Complete the entire course of therapy even if feeling better
- Report any signs of allergic reaction (rash, hives, swelling, difficulty breathing)
- Report severe diarrhea, abdominal pain, or bloody stools
- Use additional contraceptive methods if taking oral contraceptives
- Space doses evenly throughout the day
- Store suspension in refrigerator and discard after 14 days
- Do not share medication with others
- Return for follow-up if symptoms do not improve within 48-72 hours
References
1. Lexicomp Online®. Amoxicillin monograph. Wolters Kluwer Clinical Drug Information, Inc. 2023. 2. Micromedex® Solutions. Amoxicillin drug information. IBM Watson Health. 2023. 3. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Amoxicillin. 2023. 4. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 2022. 5. FDA Prescribing Information: Amoxicillin. Accessed October 2023. 6. Bradley JS, et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76. 7. World Health Organization. Model Formulary. 2021.