Clavulanate (Clavulanic Acid)
Clavulanate is a beta-lactamase inhibitor combined with amoxicillin or ticarcillin to extend the activity of these antibiotics against beta-lactamase-producing bacteria. It has minimal intrinsic antibacterial activity but protects the partner antibiotic.
- Chemical formula
- C8H9NO5
- CAS number
- 58001-44-8
- ATC code
- J01CR02
- Molecular weight
- 199.16 g/mol
- Drug class
- Beta-lactamase inhibitor
- Also known as
- Clavulanic acid, Clavulanato
What is it?
Clavulanate, also known as clavulanic acid, is a naturally occurring beta-lactam first isolated from Streptomyces clavuligerus. It has minimal intrinsic antibacterial activity but inhibits many bacterial beta-lactamases. Clavulanate is supplied only in combination with another beta-lactam antibiotic, most commonly amoxicillin (amoxicillin-clavulanate, sometimes called co-amoxiclav). It is dispensed only on prescription and is part of the World Health Organization List of Essential Medicines.
Mechanism of action
Clavulanate binds irreversibly to the active site of many class A beta-lactamases produced by bacteria, acting as a 'suicide inhibitor'. By inactivating these enzymes, it protects the companion antibiotic — usually amoxicillin — from hydrolysis and restores activity against beta-lactamase-producing organisms such as Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and many anaerobes. Clavulanate is less effective against AmpC and extended-spectrum beta-lactamases.
Pharmacokinetics
Clavulanate is well absorbed orally when administered in combination tablets, with bioavailability of approximately 60%. Plasma protein binding is around 25%. Approximately 30% to 40% of the dose is excreted unchanged in urine, with the remainder metabolised. The terminal half-life is about one hour, similar to amoxicillin, which is why the two are combined in fixed-ratio formulations. Renal impairment requires dose adjustment of the combination.
Indications
Clavulanate is approved only as part of fixed-dose combinations with another beta-lactam antibiotic. The most common combination, amoxicillin-clavulanate, is used in adults and children for moderate to severe respiratory tract infections, otitis media, sinusitis, urinary tract infections, animal and human bite wounds, and selected skin and abdominal infections. According to clinical guidelines, the combination is reserved for situations where beta-lactamase-producing pathogens are likely.
Safety profile
Common adverse effects of amoxicillin-clavulanate include diarrhoea, nausea and vaginal candidiasis, generally mild to moderate. Clavulanate is associated with a higher rate of cholestatic hepatitis than amoxicillin alone, particularly in older adults and with prolonged courses. Rash and hypersensitivity reactions follow the penicillin allergy pattern. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription, with attention to penicillin allergy and previous liver reactions.
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Frequently asked questions
Why is clavulanate combined with amoxicillin? ▾
Many bacteria produce beta-lactamase enzymes that hydrolyse amoxicillin and inactivate it. Clavulanate binds these enzymes and prevents the inactivation, restoring amoxicillin's activity against beta-lactamase-producing organisms such as Haemophilus influenzae, Moraxella catarrhalis and many anaerobes. According to clinical guidelines, the combination is used for infections where these pathogens are likely, including bite wounds, sinusitis and selected respiratory infections.
Is clavulanate active on its own? ▾
Clavulanate has minimal intrinsic antibacterial activity and is not used as a single agent. Its therapeutic role is exclusively to protect a beta-lactam companion antibiotic from beta-lactamase hydrolysis. According to the prescribing information, clavulanate is supplied only in fixed-dose combinations with amoxicillin (oral and intravenous) or ticarcillin (intravenous, in some markets), and the dose ratio is set to balance efficacy and tolerability.
Why does amoxicillin-clavulanate cause more diarrhoea than amoxicillin alone? ▾
The clavulanate component contributes to gastrointestinal disturbance, in part through effects on small bowel motility and microbiota. Diarrhoea is one of the most common adverse effects of amoxicillin-clavulanate, particularly at higher doses. According to the prescribing information, taking the combination at the start of a meal can reduce gastrointestinal upset, and probiotics may help in some patients under medical supervision.
What is amoxicillin-clavulanate-associated liver injury? ▾
Amoxicillin-clavulanate is one of the most common causes of antibiotic-associated cholestatic hepatitis, particularly in older adults and with prolonged courses. The reaction is generally idiosyncratic and reversible after discontinuation, but cases of severe and rarely fatal liver injury have been reported. According to the prescribing information, jaundice or unexplained malaise during or shortly after treatment should prompt medical review.
What are the main contraindications? ▾
Amoxicillin-clavulanate is contraindicated in known hypersensitivity to penicillins or beta-lactams and in a previous history of severe hypersensitivity or amoxicillin-clavulanate-associated cholestatic jaundice or hepatic dysfunction. Caution is required in renal impairment (with dose adjustment), in glandular fever and in patients on allopurinol. According to the prescribing information, the medical history must be reviewed by a clinician before any prescription.
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