Usage
Clavulanic acid is a β-lactamase inhibitor prescribed in combination with antibiotics like amoxicillin. It is used to treat a variety of bacterial infections, including:
- Upper Respiratory Tract Infections (e.g., tonsillitis, sinusitis, otitis media)
- Lower Respiratory Tract Infections (e.g., pneumonia, acute exacerbations of chronic bronchitis)
- Genitourinary Tract Infections (e.g., cystitis, urethritis, pyelonephritis)
- Skin and Soft Tissue Infections (e.g., cellulitis, impetigo)
- Bone and Joint Infections (e.g., osteomyelitis)
- Other Infections (e.g., intra-abdominal sepsis, septicemia, peritonitis, postpartum infections)
Clavulanic acid is not used on its own. Its pharmacological classification is a β-lactamase inhibitor. It works by inhibiting β-lactamase enzymes produced by bacteria. These enzymes normally break down antibiotics like amoxicillin, making them ineffective. Clavulanic acid protects the antibiotic by preventing its degradation, thus extending its spectrum of activity.
Alternate Names
Clavulanate potassium, potassium clavulanate. It is often found in combination with antibiotics, such as amoxicillin/clavulanate potassium (brand name Augmentin).
How It Works
Pharmacodynamics: Clavulanic acid itself has little antibacterial activity. It primarily acts by irreversibly binding to β-lactamase enzymes, particularly those produced by bacteria resistant to penicillins and cephalosporins. This inactivation allows amoxicillin (or other combined antibiotics) to remain active and exert its bactericidal effects.
Pharmacokinetics: When combined with amoxicillin, clavulanic acid is well-absorbed orally. Both medications are distributed widely throughout the body, reaching therapeutic levels in various tissues and fluids. Clavulanic acid is primarily eliminated through renal excretion, with a small amount metabolized by the liver. Amoxicillin is also primarily excreted renally.
Mode of Action: Clavulanic acid is a suicide inhibitor of β-lactamase. It forms a stable covalent adduct with the enzyme’s active site, permanently disabling the enzyme’s ability to hydrolyze β-lactam antibiotics. This mechanism extends the antibacterial spectrum of amoxicillin to include β-lactamase producing strains.
Elimination Pathways: Primarily renal excretion, with minor hepatic metabolism.
Dosage
Standard Dosage
Adults: The standard dose of amoxicillin/clavulanate potassium is 500mg/125mg or 875mg/125mg every 8 or 12 hours, respectively.
Children: Pediatric dosing is weight-based and varies based on age and the severity of the infection. For children 3 months and older, the dose is typically calculated as milligrams of amoxicillin per kilogram of body weight per day, given in divided doses every 8 or 12 hours. It’s crucial to consult pediatric dosing guidelines for precise recommendations based on weight or age bands.
Special Cases:
- Elderly Patients: Monitor renal function and adjust the dose as necessary.
- Patients with Renal Impairment: Dosage adjustments are necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: Close monitoring is recommended, and dosage modifications might be required.
- Patients with Comorbid Conditions: Evaluate potential drug interactions and tailor the therapy accordingly.
Clinical Use Cases
Dosage for specific clinical scenarios should adhere to established treatment guidelines. For surgical prophylaxis, the dosage and duration are determined by the procedure’s risk of infection.
Dosage Adjustments:
Adjust dosage for patients with renal/hepatic impairment. Consider patient-specific factors and drug interactions.
Side Effects
Common Side Effects:
Diarrhea, nausea, vomiting.
Rare but Serious Side Effects:
Allergic reactions (rash, itching, hives, difficulty breathing), Clostridium difficile associated diarrhea, liver dysfunction (jaundice), blood disorders (e.g., thrombocytopenia), serum sickness-like reactions.
Long-Term Effects:
With prolonged or repeated use, potential for antibiotic resistance development or alteration of gut microbiota exists.
Contraindications
Hypersensitivity to penicillins or cephalosporins; history of amoxicillin/clavulanate-associated cholestatic jaundice or hepatic dysfunction.
Drug Interactions
Allopurinol, Probenecid, Methotrexate, Warfarin, oral contraceptives, other antibiotics. Consult a comprehensive drug interaction resource for a complete list.
Pregnancy and Breastfeeding
Generally considered safe to use during pregnancy. Small amounts are excreted in breast milk; monitor the infant for potential side effects like diarrhea or rash.
Drug Profile Summary
- Mechanism of Action: Inhibits β-lactamase enzymes.
- Side Effects: Diarrhea, nausea, vomiting, allergic reactions, C. difficile infection, liver dysfunction.
- Contraindications: Penicillin allergy, history of hepatic dysfunction associated with the drug.
- Drug Interactions: Several; consult a reference.
- Pregnancy & Breastfeeding: Generally considered safe.
- Dosage: Varies by age, weight, and infection severity.
- Monitoring Parameters: Liver function tests, renal function tests, complete blood count (with prolonged use), observe for signs of superinfection.
Popular Combinations
Amoxicillin/clavulanic acid.
Precautions
Assess for penicillin allergy. Monitor for gastrointestinal upset and signs of superinfection (e.g., candidiasis). Monitor renal and hepatic function, especially with prolonged treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Clavulanic Acid?
A: Clavulanic acid is always given in combination with an antibiotic like amoxicillin. Dosing is based on the antibiotic component and varies with age, weight, and infection. Consult appropriate references for specific recommendations.
Q2: How should I manage a patient with a penicillin allergy who needs treatment with Augmentin?
A: Amoxicillin/clavulanate is contraindicated in patients with a penicillin allergy. Alternative antibiotics should be considered.
Q3: Can Augmentin be used in pregnant or breastfeeding women?
A: Generally, it is considered safe. Consult pregnancy/lactation specific references.
Q4: What are the signs of severe allergic reaction to Augmentin?
A: Signs of a severe reaction include difficulty breathing, swelling of the face or throat, hives, severe rash, and low blood pressure. Seek immediate medical attention if these occur.
Q5: What are the most common side effects of Augmentin?
A: The most common side effects are diarrhea, nausea, and vomiting.
Q6: Can Augmentin be used to treat viral infections?
A: No, Augmentin is only effective against bacterial infections.
Q7: What should I do if a patient develops diarrhea while taking Augmentin?
A: Diarrhea can be a sign of C. difficile infection. Evaluate the patient’s symptoms and consider testing for C. difficile.
Q8: Are there any drug interactions I should be aware of when prescribing Augmentin?
A: Yes, Augmentin interacts with several medications, including allopurinol, probenecid, methotrexate, and warfarin. Consult a comprehensive drug interaction resource.
Q9: What monitoring parameters should I consider while a patient is on Augmentin?
A: Monitor for signs and symptoms of hypersensitivity reaction, hepatic dysfunction, and C.difficile infection. Long-term use may require periodic blood counts and renal/hepatic function tests.
