Potassium clavulanate is not available as a standalone drug. It is only used in combination with amoxicillin, and often the combination is simply called “amoxicillin-clavulanate” or by the most common brand name Augmentin. Therefore, the subsequent information pertains to the combination drug amoxicillin-clavulanate.
Usage
Amoxicillin-clavulanate is prescribed for a variety of bacterial infections including:
- Lower respiratory tract infections (e.g., pneumonia, bronchitis)
- Upper respiratory tract infections (e.g., sinusitis, otitis media)
- Urinary tract infections
- Skin and soft tissue infections
- Bone and joint infections
- Dental infections
Pharmacological Classification: Antibiotic, specifically a beta-lactam antibiotic. It combines a penicillin antibiotic (amoxicillin) with a beta-lactamase inhibitor (clavulanate).
Mechanism of Action: Amoxicillin inhibits bacterial cell wall synthesis, leading to bacterial cell death. Clavulanate protects amoxicillin from degradation by beta-lactamase enzymes produced by certain bacteria, thereby extending amoxicillin’s spectrum of activity.
Alternate Names
Amoxicillin-clavulanate potassium, co-amoxiclav. Augmentin is the most recognized brand name. Various generics also exist.
How It Works
Pharmacodynamics: Amoxicillin is a bactericidal antibiotic that targets bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding disrupts the final transpeptidation step of peptidoglycan synthesis, compromising the integrity of the bacterial cell wall and ultimately leading to cell lysis and death. Clavulanate is a beta-lactamase inhibitor. Beta-lactamases are enzymes produced by some bacteria that provide resistance to beta-lactam antibiotics like amoxicillin by hydrolyzing the beta-lactam ring. Clavulanate binds to and inhibits these beta-lactamases, restoring amoxicillin’s effectiveness against these resistant bacteria.
Pharmacokinetics:
- Absorption: Amoxicillin is well-absorbed orally, and the presence of clavulanate doesn’t significantly affect its absorption. Food intake can slightly delay absorption but not the total amount absorbed.
- Distribution: Both drugs distribute widely throughout the body, achieving therapeutic levels in various tissues and fluids.
- Metabolism: Amoxicillin is primarily excreted unchanged in the urine. Clavulanate undergoes some metabolism, with some metabolites also being renally excreted.
- Elimination: Both are primarily eliminated via renal excretion. Dose adjustments are necessary for patients with renal impairment.
Mode of Action/Receptor Binding: Amoxicillin’s target is the penicillin-binding proteins (PBPs) on the bacterial cell membrane. Clavulanate inhibits beta-lactamase enzymes.
Elimination Pathways: Primarily renal excretion. Some hepatic metabolism occurs for clavulanate.
Dosage
Standard Dosage
Adults:
- Mild to moderate infections: 500/125 mg every 12 hours or 250/125 mg every 8 hours.
- Severe infections: 875/125 mg every 12 hours or 500/125 mg every 8 hours.
Children:
- Dosing is weight-based: 20-45 mg/kg/day of the amoxicillin component, divided every 8 or 12 hours depending on the severity.
- Use appropriate formulations designed for children.
- Children weighing 40kg or more can follow adult dosing.
Special Cases:
- Elderly Patients: Generally, no dose adjustment is necessary unless renal impairment is present.
- Patients with Renal Impairment: Dose adjustments are necessary; consult specific guidelines based on creatinine clearance.
- Patients with Hepatic Dysfunction: Use with caution and monitor liver function.
- Patients with Comorbid Conditions: Individualized dosing may be required.
Clinical Use Cases
Dosage guidelines for these settings typically align with the treatment of the specific infections encountered in those circumstances and should be guided by institutional protocols and infectious diseases specialists. There are no specific unique dosing recommendations for these contexts.
Dosage Adjustments
Adjustments are made based on renal function, hepatic function, and other relevant clinical factors.
Side Effects
Common Side Effects
- Diarrhea
- Nausea
- Vomiting
- Rash
- Vaginal candidiasis
Rare but Serious Side Effects
- Clostridium difficile-associated diarrhea (CDAD)
- Allergic reactions (including anaphylaxis)
- Stevens-Johnson syndrome
- Liver dysfunction
- Seizures (rare)
Long-Term Effects
Potential long-term effects include antibiotic-associated colitis and the development of antibiotic resistance.
Adverse Drug Reactions (ADR)
Severe allergic reactions (anaphylaxis, angioedema) require immediate medical attention.
Contraindications
- Hypersensitivity to penicillins or cephalosporins.
- History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin-clavulanate.
Drug Interactions
- Allopurinol: Increased risk of rash.
- Oral contraceptives: Potential reduced efficacy of oral contraceptives.
- Probenecid: Increases amoxicillin levels.
- Anticoagulants (e.g., warfarin): Amoxicillin can potentiate the anticoagulant effect.
- Methotrexate: Concurrent use can increase methotrexate levels and toxicity.
Pregnancy and Breastfeeding
- Pregnancy Category B: Animal studies have not shown fetal harm, but there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.
- Breastfeeding: Amoxicillin is excreted in breast milk, and while generally considered safe, it can potentially cause diarrhea or rash in the infant.
Drug Profile Summary
- Mechanism of Action: Amoxicillin inhibits bacterial cell wall synthesis, while clavulanate inhibits beta-lactamase.
- Side Effects: Diarrhea, nausea, rash. Rarely, serious allergic reactions or C. difficile infection.
- Contraindications: Penicillin or cephalosporin allergy, prior cholestatic jaundice/hepatic dysfunction with amoxicillin-clavulanate.
- Drug Interactions: Allopurinol, oral contraceptives, probenecid, anticoagulants, methotrexate.
- Pregnancy & Breastfeeding: Use with caution in pregnancy only if clearly needed; generally considered safe during breastfeeding.
- Dosage: Refer to detailed section above.
- Monitoring Parameters: Renal function, liver function, signs of hypersensitivity.
Popular Combinations
Amoxicillin-clavulanate is often used alone.
Precautions
Standard precautions include assessing allergy history, renal and hepatic function, and considering drug interactions. Monitor patients for signs of superinfection.
FAQs
Q1: What is the recommended dosage for Potassium Clavulanate?
A: Potassium clavulanate is not prescribed on its own. It is given in conjunction with amoxicillin. Dosing is dependent on the patient, their age and weight and the severity of their illness. See the dosage section for detailed guidelines.
Q2: What infections is amoxicillin-clavulanate typically used for?
A: Amoxicillin-clavulanate is used for a broad range of infections, including respiratory tract infections (pneumonia, bronchitis, sinusitis, otitis media), urinary tract infections, skin and soft tissue infections, and some other bacterial infections.
Q3: What is the role of clavulanate in the combination?
A: Clavulanate is a beta-lactamase inhibitor. It prevents some bacteria from breaking down amoxicillin, making the antibiotic effective against a wider range of bacteria.
Q4: What are the most common side effects?
A: Common side effects include diarrhea, nausea, vomiting, and skin rashes.
Q5: Are there any serious side effects to be aware of?
A: Yes. Though rare, serious side effects can include Clostridium difficile infection (CDAD), severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome, and liver dysfunction.
Q6: What are the contraindications to using this drug?
A: Amoxicillin-clavulanate is contraindicated in patients with a history of hypersensitivity to penicillins, cephalosporins, or any component of the formulation and in those with previous cholestatic jaundice or hepatic dysfunction associated with amoxicillin-clavulanate use.
Q7: How should the dosage be adjusted for patients with renal impairment?
A: Dosage adjustments are based on the degree of renal impairment (creatinine clearance). Consult specific guidelines.
Q8: Can amoxicillin-clavulanate be used during pregnancy and breastfeeding?
A: It’s a Pregnancy Category B drug. While animal studies have not demonstrated harm, its use in pregnant women should be carefully considered and limited to situations where the benefits outweigh the potential risks. It is generally considered safe to use during breastfeeding, but monitor the infant for potential side effects like diarrhea and rash.
Q9: How does this drug interact with other medications?
A: Amoxicillin-clavulanate has interactions with several drugs, including allopurinol, oral contraceptives, probenecid, anticoagulants (e.g., warfarin), and methotrexate.
Q10: What patient education should be provided regarding amoxicillin-clavulanate use?
A: Patients should be advised to take the medication as prescribed for the full duration of therapy, even if symptoms improve. They should report any signs of allergic reactions immediately. Also advise patients to take the medication with food to reduce gastrointestinal upset and report any severe or persistent diarrhea. Inform patients about the potential for reduced efficacy of oral contraceptives while using amoxicillin-clavulanate.
