In a previous issue of this bulletin (Vol.
7, No. 4 - October, 1998) we had drawn attention to the
potential hepatotoxicity of amoxicillin-clavulanic acid
combination which is also known as co-amoxiclav. In view
of the increasingly blind use of this combination,
particularly in treating respiratory tract and ENT
infections notwithstanding the high cost, the warning
needs to be reinforced. Otherwise a potentially
life-saving drug can end up causing greater morbidity
than it relieves.
Cholestatic jaundice has occurred during or upto 6 weeks
after use of co-amoxiclav. The hepatotoxicity has been
attributed to the clavulanic acid component since
amoxicillin alone rarely causes liver damage. It appears
to be more common in male and in the elderly. In view of
these findings the British Committee on safety of
medicines has advised that the combination be used with
caution, the duration of treatment should be appropriate
to the indication and should not generally exceed 14
days. Fortunately, jaundice due to co-amoxiclav is
usually self-limiting and is rarely fatal.
In critical care situations the combination is being used
extensively. However, it is in this very situation that
patients with hepatic impairment are likely to be
encountered. Hence doctors looking after ITU patients
need to be extra careful when ordering co-amoxiclav and
should review their decision to use this combination
vis-à-vis other effective antibiotics.
The oral (amoxicillin trihydrate + clavulanate potassium)
and parenteral (amoxicillin sodium + clavulanate
potassium) formulations of co-amoxiclav that are
currently available in the Indian market are shown in the
following table.
British National
Formulary 1998; No. 35 (March, 1998): 241.
Rene JM, et al.
Hepatotoxicity caused by amoxicillin-clavulanic
acid. Gastroenterol Hepatol 1997; 20 (6): 337-8.
Bralet MP, et al.
Hepatitis caused by the amoxicillin-clavulanic
acid combination: an example of drug-induced
biliary hepatotoxicity. Ann Pathol 1996; 16 (6):
425-9.
Acute pancreatitis
associated with hepatotoxicity induced by
amoxicillin-clavulanic acid. Rev Esp Enferm Dig
1995; 87 (8): 597-600.
Larrey D, et al.
Hepatitis associated with amoxicillin-clavulanic
acid combination: report of 15 cases. Gut 1992;
33 (3): 368-71.
Peroux JL, et al.
Augmentin hepatotoxicity: responsibility of
clavulanic acid? Apropos of a case. Gastroenterol
Clin Biol 1992; 16 (1): 102-3.
Alexander P, et al.
Intrahepatic cholestasis induced by amoxicillin /
clavulanic acid (Augmentin): a report on two
cases. Acta Clin Belg 1991; 46 (5): 327-32.
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