Clavulanic acid (Potassium Clavulanate)
Introduction
- Clavulanic acid is the β-lactamase inhibitor.
- It is obtained from Streptomyces clavuligerus. It has a β-lactam ring but no antibacterial activity of its own.
- It inhibits a wide variety (class II to class V) of β-lactamases (but not class I cephalosporinase) produced by both gram-positive and gram-negative bacteria.
- Clavulanic acid is a ‘progressive’ inhibitor : binding with β-lactamase is reversible initially, but becomes covalent later-inhibition increasing with time.
- It is also called as a ‘suicide’ inhibitor because it gets inactivated after binding to the enzyme.
- It permeates the outer layers of the cell wall of gram-negative bacteria and inhibits the periplasmically located β-lactamase.
Pharmacokinetics
- Clavulanic acid has rapid oral absorption; can also be injected.
- Route : Oral, IV
- Oral bioavailability : 60%
- Metabolism : Hepatic (extensive)
- Plasma half life : 1 hour
- Its elimination half life and tissue distribution matches amoxicillin with which it is used (called Coamoxiclav). However, it is eliminated mainly by glomerular filtration and its excretion is not affected by probenecid. Also, it is largely hydrolysed and decarboxylated before excretion, while amoxicillin is primarily excreted unchanged by tubular secretion.
Clinical & Chemical data
- Dose :
- Pregnancy risk category : B
- Chemical formula : C8H9NO5
- IUPAC name : (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid
Uses
- Addition of clavulanic acid re-establishes the activity of amoxicillin against β-lactamase producing resistant Staph. aureus (but not MRSA that have altered PBPs), H. influenzae, N. gonorrhoeae, E. coli, Proteus, Klebsiella, Salmonella and Shigella.
- Bact. fragilis and Branhamella catarrhalis are not responsive to amoxicillin alone, but are inhibited by the combination. Amoxicillin sensitive strains are not affected by the addition of clavulanic acid.
Coamoxiclav is indicated for :
- Skin and soft tissue infections, intra-abdominal and gynaecological sepsis, urinary, biliary and respiratory tract infections: especially when empiric antibiotic therapy is to be given for hospital acquired infections.
- Gonorrhoea (including PPNG) single dose amoxicillin 3 g + clavulanic acid 0.5 g + probenecid 1 g is highly curative.
Besides Amoxicillin, Potassium clavulanate is combined with ticarcillin (co-ticarclav).
Side effects
Side effects are the same as for amoxicillin alone; g.i. tolerance is poorer-especially in children. Other side effects are Candida stomatitis/ vaginitis and rashes. Some cases of hepatic injury have been reported with the combination.
Trade names
- Co-amoxiclav is available as Augmentin, Enhancin, Amonate, Clavam, Tyclav.
- Co-ticarclav is available as Timentin.
For detailed query or in case of uncertainty, Always consult your doctor or pharmacist.
