Liver amoxicillin

Metabolism may be mediated by intestinal microflora, epithelial enzymes, or liver enzymes preceding entry into the systemic circulation. Chloramphenicol is well absorbed when administered orally to calves less than 1 week old, but it is inactivated by microflora when administered to ruminants. Similar observations have been made after oral administration of amoxicillin, ampicillin, and cephalexin therapy in young calves (11). On the other hand, trimethoprim, which is extensively metabolized in the liver and may undergo some metabolism in the rumen, shows higher systemic availability in the newborn calf and kid, due probably to the lower metabolic activity in the neonatal animal. 

If a patient has cholestasis careful consideration must be given to the use of any drug that can cause biliary problems. Several drugs are known to cause cholestatic hepatitis, including the antibiotics flucloxacillin, erythromycin and co-amoxiclav (amoxicillin/clavulanic acid). Although a patient with cholestasis is no more likely to suffer from this idiosyncratic reaction than a patient without liver impairment, it will be of greater concern if it does occur. 

Co-amoxiclav can cause cholestatic hepatitis. The first report appeared in 1988 (14), since when several hundreds of cases have been reported, for example to health authorities (15), and over 100 cases have been described in detail (16-31). Clavulanic acid is instrumental, either alone or in combination with amoxicillin, since the risk of acute liver injury is much smaller with amoxicillin alone (32). 

The relative contributions of amoxicillin and clavula-nate to co-amoxiclav-induced hepatotoxicity are incompletely understood. In patients with co-amoxiclav hepatotoxicity, previous use of amoxicillin and rechallenge with amoxicillin were both uneventful, pointing to clavulanic acid as the more likely culprit (16). In a report from the UK, the incidence of liver injury with amoxicillin alone was 0.3 per 10000 prescriptions versus 1.7 with co-amoxiclav (32). The risk increased after multiple use and with increasing age to 1 per 1000 prescriptions of co-amoxiclav. The main message is that the combination should be used with caution in elderly patients. A patient who has had documented hepatotoxicity related to co-amoxiclav should be well informed about this adverse drug reaction and any future use should be prohibited. 

Maggini M, Raschetti R, Agostinis L, Cattaruzzi C, Troncon MG, Simon G. Use of amoxicilhn and amoxicillin-clavulanic acid and hospitalization for acute liver injury Ann 1st Super Sanita 1999 35(3) 429-33. 

The MACH-2 study has assessed the role of omeprazole in triple therapy in 539 patients with duodenal ulcers associated with H. pylori (3). The addition of omeprazole resulted in significantly higher eradication rates (over 90%) than antibiotics alone (amoxicillin plus clarithromycin about 25% clarithromycin plus metronidazole 70%), and reduced the impact of primary resistance to metronidazole. About one-third of the patients who took amoxicillin reported diarrhea/loose stools. The frequency of taste disturbance was dose-dependent with clarithromycin. Increased liver enzymes were more commonly reported in those taking metronidazole. The addition of omeprazole did not increase the frequency of reported adverse effects. 

An animal study found that diclofenac caused an 8.5-fold reduction in amoxicillin serum levels, when compared with amoxicillin alone. However, amoxicillin retained its efficacy despite lowered serum levels and it was suggested that diclofenac was unlikely to cause an increase in renal clearance of amoxicillin, nor an etfect on its liver metabolism. These studies therefore suggest that a clinically significant interaction would not be expected. 

Hepatitis and jaundice caused by the combination of amoxicillin and clavulanic acid were first identified in 1988. The combination of the two drugs is associated with a higher incidence of liver injury than the administration of amoxicillin alone. The risk of this drug-induced liver injury, mostly cholestatic in nature, increases with age and by about a factor of 3 after 2 or more consecutive courses of drug. 

The combination of amoxicillin and clavulanic acid is associated with the risk of drug-induced liver injury, mostly cholestatic in nature. 

An 8-year-old boy with a history of a liver transplant at 4 years of age was treated with amoxicillin (25 mg/ kg/day)/clavulanic acid (3.6 mg/kg/day) for 2 weeks for the treatment of a URTI. The patient had tolerated amoxicillin/clavulanate in the past. Two days after discontinuation of amoxicillin/clavulanic treatment, the patient was admitted with jaxmdice and abnormal liver fxmction tests (AST 961/U, ALT 2271/U, total bilirubin 6.9 mg/dL and direct bilirubin 5.3 mg/dL). Per the authors, the histopathological presentation was consistent with drug-induced liver injury. The patient was treated with methylprednisolone (10 mg/kg/day) and ursodeoxycholic acid (20 mg/kg/day), with full resolution 12 weeks after the patient initially presented. Of note, improvement in liver enzymes was seen before these therapies were initiated. The patient developed two episodes of elevated transaminases during a 7-year follow-up, but the liver biopsies performed at those times were nonspecific [27 ]. 

A Spanish study examined causes of amoxicillin/clavulanate-induced liver injury to determine the role of HLA class 1 and 11 alleles in characteristics of this effect. It was found that different alleles may influence the type of presentation of liver injury (hepatocellular vs cholestatic), severity and timing of onset [29 ]. 

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