Amoxicillin

1. Drug Name

• Generic Name: Amoxicillin

• Brand Names: Amoxil, Trimox, Moxatag, Amoxicot, Polymox, and others.

2. Drug Classification

• Class: Antibiotic, Penicillin (Beta-lactam)

• Subclass: Aminopenicillin

3. Mechanism of Action

• Primary Action: Amoxicillin works by inhibiting bacterial cell wall synthesis. It binds to and inactivates penicillin-binding proteins (PBPs) that are involved in the final stages of cell wall formation. The disruption of the cell wall results in bacterial lysis and death, especially in dividing bacteria.

• Spectrum of Activity: Amoxicillin is active against a broad range of gram-positive and gram-negative bacteria, including Streptococcus, Haemophilus influenzae, Escherichia coli, Neisseria gonorrhoeae, and some strains of Enterococcus. However, it is less effective against beta-lactamase-producing bacteria and is often combined with beta-lactamase inhibitors like clavulanic acid to extend its spectrum.

4. Pharmacokinetics

• Absorption: Amoxicillin is well absorbed from the gastrointestinal tract, with bioavailability around 93%. Food does not significantly affect its absorption.

• Distribution: Amoxicillin is widely distributed throughout the body, reaching therapeutic concentrations in the blood, tissues, and fluids, including urine, lungs, and middle ear. It crosses the placenta and is excreted in breast milk.

• Metabolism: It is minimally metabolized in the liver. Amoxicillin remains largely unchanged in the body.

• Excretion: Excreted primarily by the kidneys via glomerular filtration and tubular secretion. The half-life of amoxicillin is approximately 1 to 1.5 hours in individuals with normal renal function.

• Special Considerations: In patients with renal dysfunction, dose adjustments may be necessary, especially in those with a creatinine clearance <30 mL/min, as the drug is cleared via the kidneys.

5. Indications

• Primary Indications:

  • Respiratory tract infections (e.g., pneumonia, bronchitis, sinusitis, and otitis media).

  • Urinary tract infections (UTIs), including cystitis and pyelonephritis.

  • Skin and soft tissue infections.

  • Helicobacter pylori eradication (as part of a combination therapy).

  • Gonorrhea (uncomplicated).

  • Endocarditis prophylaxis in certain patients (e.g., those with heart valve disease undergoing dental procedures).

  • Lyme disease (early stage).

• Off-label Uses:

  • Prophylaxis for dental infections in patients with specific heart conditions.

  • Treatment of Helicobacter pylori in peptic ulcer disease in combination with other drugs.

• Specific Populations: Amoxicillin is generally safe and effective in children and pregnant women (Category B), but dose adjustments may be necessary in patients with renal impairment.

6. Dosage and Administration

• Adult Dosing:

  • Infections (e.g., respiratory, UTI, skin infections): The usual dose is 250–500 mg every 8 hours or 500–875 mg every 12 hours. The dose can be increased based on infection severity.

  • Helicobacter pylori eradication: 1,000 mg twice daily in combination with other agents (e.g., clarithromycin and a proton pump inhibitor).

  • Endocarditis prophylaxis: 2,000 mg orally 1 hour before the procedure.

• Pediatric Dosing:

  • Respiratory tract infections and ear infections: 20–40 mg/kg/day in divided doses every 8–12 hours.

  • UTIs: 25–50 mg/kg/day in divided doses every 8 hours.

  • Maximum dose: The usual maximum dose in pediatric patients is 1,000 mg per dose.

• Renal/Hepatic Adjustments: In cases of renal impairment (e.g., CrCl <30 mL/min), the dose should be adjusted. No dose adjustment is needed for hepatic dysfunction.

• Route of Administration: Oral (tablets, capsules, liquid suspension), intravenous (for severe infections).

7. Contraindications

• Absolute Contraindications:

  • Hypersensitivity to amoxicillin, penicillins, or any component of the formulation.

  • History of a severe allergic reaction to any beta-lactam antibiotics (penicillins, cephalosporins).

• Relative Contraindications:

  • Caution in patients with a history of allergic reactions to other antibiotics, particularly cephalosporins.

  • Use with caution in patients with renal impairment or a history of gastrointestinal disease (e.g., colitis).

8. Warnings and Precautions

• Allergic Reactions: Serious hypersensitivity reactions, including anaphylaxis, can occur. Discontinue amoxicillin immediately if any signs of an allergic reaction (e.g., rash, hives, difficulty breathing, swelling of the throat) are observed.

• Clostridium difficile-associated Diarrhea (CDAD): Can occur with antibiotics, including amoxicillin. It can range from mild diarrhea to life-threatening colitis.

• Renal Function: Caution is needed in patients with renal impairment, and dose adjustments are recommended. Monitor renal function during prolonged use.

• Pregnancy and Lactation: Amoxicillin is classified as Pregnancy Category B, indicating no risk to the fetus in human studies. It is excreted in breast milk but is generally considered safe for use during breastfeeding.

9. Adverse Effects

• Common Adverse Effects (≥10%):

  • Diarrhea

  • Nausea

  • Rash (mild)

  • Vomiting

  • Abdominal pain

• Less Common but Clinically Significant:

  • Allergic reactions: anaphylaxis, urticaria, angioedema

  • Oral candidiasis (thrush)

  • Vaginal yeast infections

  • Pseudomembranous colitis (Clostridium difficile infection)

• Serious Adverse Reactions:

  • Severe allergic reactions: anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis

  • Hematologic: thrombocytopenia, leukopenia, agranulocytosis

  • Liver toxicity: hepatitis, cholestatic jaundice

  • Renal toxicity: interstitial nephritis

10. Drug Interactions

• Major Drug Interactions:

  • Probenecid: Increases the serum concentration of amoxicillin by inhibiting renal tubular secretion, potentially leading to higher levels.

  • Methotrexate: Amoxicillin can reduce renal clearance of methotrexate, increasing the risk of methotrexate toxicity.

  • Oral Contraceptives: While not commonly associated, there is some evidence suggesting that antibiotics like amoxicillin may reduce the efficacy of oral contraceptives. Alternative or additional contraception should be considered during therapy.

  • Allopurinol: The concurrent use of amoxicillin and allopurinol may increase the risk of developing a rash.

• Food-Drug Interactions: Food does not significantly alter the absorption of amoxicillin, but it is generally recommended to take it with food to reduce gastrointestinal upset.

• Lab Test Interference: Amoxicillin can cause false-positive results in tests for urinary glucose (especially with non-enzyme-based methods), and this should be considered when interpreting lab results.

11. Clinical Pharmacology

• Pharmacodynamics: Amoxicillin’s bactericidal action results from the inhibition of bacterial cell wall synthesis. It is a broad-spectrum antibiotic, meaning it is effective against a wide range of bacterial species.

• Additional Effects: Amoxicillin has a relatively short half-life, requiring multiple doses per day. It is effective in both outpatient and inpatient settings, with oral formulations being suitable for outpatient treatment of common infections.

12. Special Populations

• Pregnancy: Category B – No evidence of risk to the fetus in human studies. Amoxicillin is generally considered safe for use during pregnancy, though it should be used only when clearly needed.

• Lactation: Amoxicillin is excreted into breast milk in small amounts, but it is considered safe for use in breastfeeding mothers.

• Pediatrics: Safe and effective for use in children. Dosing is based on weight, and careful monitoring is required, especially for neonates and infants.

• Geriatrics: Older adults may be more susceptible to the toxic effects of antibiotics, especially if they have comorbidities like renal insufficiency.

13. Therapeutic Uses

• First-Line Use:

  • Amoxicillin is commonly used as a first-line treatment for a variety of infections, including otitis media, sinusitis, pharyngitis, bronchitis, and urinary tract infections.

• Combination Therapy:

  • In combination with other agents, such as clavulanic acid (to form co-amoxiclav), amoxicillin is used to treat infections caused by beta-lactamase-producing bacteria, including sinusitis, bronchitis, and some skin infections.

• Clinical Trials and Efficacy:

  • Numerous clinical trials support the efficacy of amoxicillin in treating a wide range of bacterial infections, demonstrating its role as a standard treatment in the outpatient setting for respiratory and urinary tract infections.

14. Monitoring and Follow-Up

• Lab Tests: Periodic liver function tests and renal function monitoring are recommended in patients receiving prolonged therapy, particularly in those with preexisting liver or kidney dysfunction.

• Patient-Reported Symptoms: Patients should be monitored for any signs of rash, gastrointestinal distress, or signs of severe allergic reactions.

• Monitoring of Therapeutic and Toxic Levels: While therapeutic drug monitoring is not routinely necessary, amoxicillin should be used with caution in patients with renal impairment.

15. Overdose Management

• Symptoms of Overdose: Symptoms of overdose include nausea, vomiting, diarrhea, and gastrointestinal disturbances.

• Treatment Protocols: In the event of overdose, symptomatic treatment should be provided. Activated charcoal may be administered if ingestion occurred within a few hours of overdose.

• Supportive Measures: No specific antidote exists. Treatment involves supportive care such as rehydration and electrolyte balance.

16. Patient Counseling Information

• Key Points to Discuss with Patients:

  • Advise patients to complete the full course of therapy, even if they feel better, to prevent the development of antibiotic resistance.

  • Take with food if gastrointestinal upset occurs.

  • Inform patients to report any signs of allergic reactions (e.g., rash, difficulty breathing, swelling).

• Signs/Symptoms to Watch For:

  • Immediate medical attention is required if symptoms of an allergic reaction, such as anaphylaxis, occur.

  • Inform healthcare providers if diarrhea, abdominal pain, or black stools develop, which may suggest a serious infection like Clostridium difficile.