Usage
Amoxycillin + Clavulanic acid is prescribed for a variety of bacterial infections. These include infections of the lower and upper respiratory tract (e.g., pneumonia, bronchitis, sinusitis, tonsillitis, otitis media), genitourinary tract (e.g., cystitis, pyelonephritis), skin and soft tissue (e.g., cellulitis, abscesses), bones and joints, and other infections such as dental abscesses, intra-abdominal infections, and animal bites. It is also used for surgical prophylaxis, particularly in operative vaginal delivery. This medication belongs to the pharmacological classification of antibiotics, specifically beta-lactam antibiotics combined with a beta-lactamase inhibitor.
Amoxycillin works by inhibiting bacterial cell wall synthesis, leading to bacterial cell death. Clavulanic acid, a beta-lactamase inhibitor, prevents the breakdown of amoxycillin by bacterial enzymes (beta-lactamases), thus extending amoxycillin’s effectiveness against a broader spectrum of bacteria, including those resistant to amoxycillin alone.
Alternate Names
Amoxycillin + Clavulanic Acid is also known as co-amoxiclav. A popular brand name under which it is marketed is Augmentin.
How It Works
Pharmacodynamics: Amoxycillin, a penicillin-like antibiotic, exerts bactericidal effects by interfering with the synthesis of bacterial cell walls. It inhibits transpeptidases and carboxypeptidases, enzymes essential for peptidoglycan cross-linking, which is a crucial step in bacterial cell wall construction. This disruption weakens the cell wall, leading to cell lysis and bacterial death. Clavulanic acid is a beta-lactamase inhibitor, irreversibly binding to and inactivating these bacterial enzymes. Many bacteria produce beta-lactamases to resist the effects of beta-lactam antibiotics such as amoxycillin. Clavulanic acid broadens the spectrum of amoxycillin activity by making it effective against bacteria that would otherwise be resistant due to beta-lactamase production.
Pharmacokinetics:
- Absorption: Amoxycillin + Clavulanic acid is well-absorbed orally. Administration with food, especially at the start of a meal, can minimize gastrointestinal intolerance and optimize absorption.
- Distribution: The drug is widely distributed throughout the body, including into various tissues and fluids.
- Metabolism: Amoxycillin is partially metabolized in the liver. Clavulanic acid undergoes extensive metabolism.
- Elimination: Both components are primarily eliminated through renal excretion. Dosage adjustments are necessary in patients with renal impairment.
Dosage
Standard Dosage
Adults:
- Mild to Moderate Infections: Amoxycillin/Clavulanate 500mg/125mg every 12 hours or 250mg/125mg every 8 hours.
- Severe Infections: Amoxycillin/Clavulanate 875mg/125mg every 12 hours. Extended-release formulations (1000mg/62.5mg) are also available and administered every 12 hours.
Children (3 months and older):
Dosing in children is weight-based and generally ranges from 20mg/5mg/kg/day to 90mg/6.4mg/kg/day of amoxycillin/clavulanic acid, divided into doses given every 8 or 12 hours. Consult the sources for examples of practical dosing regimens based on weight. Children weighing 40 kg or more can generally receive adult doses.
Special Cases:
- Elderly Patients: May require dosage adjustments due to age-related decline in renal function.
- Patients with Renal Impairment: Dosage adjustments are needed based on the degree of impairment. For creatinine clearance (CrCl) less than 30 mL/min, specific dosage reductions or increased dosing intervals are essential. Hemodialysis patients require additional doses during and after dialysis.
- Patients with Hepatic Dysfunction: Exercise caution and monitor liver function. Dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Consider potential interactions with other medications, particularly those metabolized by the liver or kidneys.
Clinical Use Cases
Dosing for surgical prophylaxis, such as operative vaginal delivery, typically involves a single intravenous dose of 1.2g or an oral dose of 875mg/125mg administered within 6 hours of delivery. Consult specific guidelines for dosage recommendations in other clinical scenarios such as intubation, mechanical ventilation, and ICU care, as dosages may vary. The duration of treatment usually ranges from 3 to 14 days depending on the infection and patient response.
Dosage Adjustments
Dose modifications are crucial for patients with renal or hepatic dysfunction, as well as in elderly patients. In severe infections, higher doses or more frequent administration may be necessary. For prolonged high-dose treatment, monitor complete blood count and renal and hepatic function.
Side Effects
Common Side Effects:
Diarrhea, nausea, vomiting, vaginal itching or discharge, diaper rash, headache, abdominal pain.
Rare but Serious Side Effects:
Allergic reactions (rash, itching, hives, swelling, difficulty breathing), severe stomach pain, watery or bloody stools, fever, liver injury (jaundice, right upper belly pain), unusual bleeding or bruising, severe vomiting, peeling or blistering skin.
Long-Term Effects:
Chronic complications are rare with short-term use. Long-term use can lead to antibiotic resistance and changes in gut flora.
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis), Clostridium difficile-associated diarrhea, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Contraindications
- History of hypersensitivity to penicillins or cephalosporins.
- Previous cholestatic jaundice/hepatic dysfunction associated with amoxycillin/clavulanate use.
- Phenylketonuria (for formulations containing aspartame).
Drug Interactions
Amoxycillin/clavulanate can interact with various medications:
- Allopurinol: Increased risk of rash.
- Probenecid: Increased amoxycillin levels.
- Methotrexate: Increased methotrexate levels, potential toxicity.
- Warfarin: Increased anticoagulant effect, bleeding risk.
- Oral contraceptives: Potential decreased efficacy of oral contraceptives, though clinically significant interactions are unlikely.
- Tetracyclines: May decrease the efficacy of amoxycillin.
Pregnancy and Breastfeeding
Amoxycillin/clavulanate is generally considered safe during pregnancy (Pregnancy Category B). Although it is excreted in breast milk, the levels are low and typically do not cause harm to the infant. Monitoring for infant side effects (rash, diarrhea, irritability) is advised.
Drug Profile Summary
- Mechanism of Action: Amoxycillin inhibits bacterial cell wall synthesis, while clavulanic acid protects amoxycillin from beta-lactamase degradation.
- Side Effects: Common: diarrhea, nausea, vomiting, rash. Serious: allergic reactions, liver injury, C. difficile infection.
- Contraindications: Penicillin hypersensitivity, history of cholestatic jaundice/hepatic dysfunction associated with the drug.
- Drug Interactions: Allopurinol, probenecid, methotrexate, warfarin, tetracyclines.
- Pregnancy & Breastfeeding: Generally safe.
- Dosage: Adults: 250mg/125mg to 875mg/125mg every 8 or 12 hours. Children: weight-based dosing.
- Monitoring Parameters: Renal and hepatic function, complete blood count (for prolonged high-dose treatment).
Popular Combinations
No consistently popular drug combinations are explicitly mentioned in the sources.
Precautions
- General Precautions: Screen for allergies to penicillin or cephalosporins. Assess renal and hepatic function before and during treatment, especially with prolonged use.
- Specific Populations: Monitor infants of breastfeeding mothers for any adverse effects. Dosage adjustments are necessary in patients with renal/hepatic impairment and elderly patients.
- Lifestyle Considerations: Alcohol may increase the risk of gastrointestinal side effects. No specific driving restrictions are usually associated with this medication.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amoxycillin + Clavulanic Acid?
A: Dosing varies depending on the patient’s age, weight, the severity of the infection, and renal function. Adults typically receive 250mg/125mg to 875mg/125mg every 8 to 12 hours. Pediatric dosing is weight-based.
Q2: What are the most common side effects?
A: Diarrhea, nausea, vomiting, and rash are the most common side effects.
Q3: Is Amoxycillin + Clavulanic Acid safe during pregnancy?
A: It is generally considered safe to use during pregnancy.
Q4: How should this medication be administered?
A: Take it orally with food, preferably at the start of a meal to optimize absorption and minimize gastrointestinal upset.
Q5: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it is close to the time for the next dose. Do not double the dose.
Q6: What are the serious adverse reactions associated with this drug?
A: Serious side effects include allergic reactions (anaphylaxis), C. difficile infection, liver injury, and severe skin reactions. Seek immediate medical attention if these occur.
Q7: Can I drink alcohol while taking this medication?
A: Alcohol may increase the risk of gastrointestinal side effects. Limiting alcohol consumption during treatment is advisable.
Q8: How does clavulanic acid enhance the effectiveness of amoxycillin?
A: Clavulanic acid inhibits beta-lactamases, bacterial enzymes that would otherwise break down amoxycillin, making amoxycillin effective against a wider range of bacteria.
Q9: What infections is Amoxycillin/Clavulanic Acid used to treat?
A: It treats various bacterial infections, including respiratory, genitourinary, skin, and soft tissue infections, as well as others like dental abscesses.
Q10: Are there any specific considerations for patients with renal impairment?
A: Yes, dosage adjustments are essential for patients with renal impairment based on their creatinine clearance.
