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[e-drug] clavulanic acid (ir)ratios

E-DRUG: clavulanic acid (ir)ratios
[we continue a critical review of the essential drugs market. WB]

dear E-druggers,

Clavulanic acid is used as a beta-lactamase inhibitor in fixed dose
combinations with (inter alia) amoxicillin. It has hardly any antibacterial
activity itself, but it can extend the clinical use of amoxicillin against
beta-lactamase producing bacteriae.
Normally, 250 or 500mg amoxicillin is combined with 125mg clavulanic acid
(a 2:1 or 4:1 ratio). The maximum recommended daily dose of clavulanic acid
is 500mg.

The  500+125mg tablet (4:1 ratio) is the one in the current WHO EDL as a
reserve antibiotic.

Sometimes (e.g., chronic otitis media) there are valid indications to
increase the amoxicillin dose. This should be done by adding plain
amoxicillin, as the maximum dose of clavulanic acid is already provided in
the basic combination product.

Taking 2 tablets of 250+125 is NOT the same as one 500+125 tablet! It
provides the double dose of clavulanic acid, which has been linked to
increased risks of cholestatic hepatotoxicity.

The original manufacturer obviously prefers to sell a (more expensive)
combination product (rather than selling more plain amoxicillin, of which
there are many generic competitors!), and is therefore also marketing fixed
dose combinations with higher ratios. For example, it markets also chewable
tablets of 400+57mg, a 7:1 ratio. However, all 2:1, 4:1 and 7:1 products
run under the same brandname Augmentin!

There are also 125+32.25 (4:1), 250+62.5 (4:1), 200+28.5 (7:1) and 400+57
(7:1) suspensions available (all per 5 mL, under the same brandname
Augmentin). In some countries, there is even a  600+42.9mg/5mL suspension
(14:1 ratio, brandname Augmentin ES-600).

In some countries (where there was no patent, or the Augmentin patent
expired) generics are available with 250+62.5 mg...

Are you as confused as I am?

If the amoxicillin-clavulanic acid ratios vary 7-fold from 2:1 to 14:1, it
sounds logical to do away with a fixed dose combination, and to market
clavulanic acid separately from amoxicillin. "Loose" clavulanic acid is
however not available from the original manufacturer (not profitable?).

So why don't we develop generic clavulanic acid 125mg tablets, and do away
with the fixed dose confusion?

Would this not allow simpler prescribing/dosing, and also prevent the
overdosing of clavulanic acid?

However, as clavulanic acid has no intrinsic antibacterial activity, could
it be registered as a medicine?

Your comments are welcome!

Wilbert Bannenberg

Dr Wilbert Bannenberg, E-drug moderator
Box 456, Irene 0062, South Africa
Mobile +27-82-5756249
Tel +27-12-6671752
Fax +27-12-6671762
Email: WilbertBannenberg@compuserve.com

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