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​​​Antimicrobials in hepatic impairment


The Child-Pugh scoring system aims to classify the severity of liver disease; it does not determine the livers ability to clear medications.  

The scoring system can be seen in the table below:​​​​​

​​ 

Parameter​

Score

 

​1

2

3

Ascites

None​

Moderate or 

easily treated

Severe or intrac​table

Encephalopathy grade

None

1-2

3-4

Bilirubin

(micromole/L)

OR

Bilirubin in Primary biliary cirrhosis

(micromole/L)

<35

 

 

<70

35-50

 

 

7​0-170

>50

 

 

>170

Albumin

>35

28-35

<28

INR

<1.7

1.8-2.3

>2.3

​ ​

Mild impairment: Child-Pugh A is a score of 5-6 indicating a well-compensated liver.

Moderate impairment: Child-Pugh B is a score of 7-9 indicating significant functional compromise.

Severe impairment: Child-Pugh C is a score of 10-15 indicating a decompensated liver. 


The BNF and Summary of Product Characteristics (SPC) will advise on dose reductions of some medications based on either ‘mild, moderate or severe impairment’ or based on the patients Child-Pugh score. If the SPC does not advise regarding dosing in patients with hepatic impairment, it is important to consider both patient-specific factors and drug-specific factors before reducing the dose of some medications.

Firstly, consider the patient and their diagnosis, the trend of the liver function tests and their signs/symptoms of liver disease. Secondly, the pharmacokinetics of the drug should be reviewed and how it will be impacted in hepatic impairment.

For example, if a patient’s hepatic function is acutely deranged due to infection, and not thought to be cirrhotic, then a dose reduction would be inappropriate. Be mindful of using nephrotoxic medications in patients with decompensated liver disease due to the risk of hepatorenal syndrome.

Please contact your pharmacist for further advice. ​ 

The following antimicrobials need careful consideration in hepatic impairment:​ 

Antimicrobial

Advice

Azithromycin

    •  Consider alternative in patients with severe liver diseases.
    •  Azithromycin is metabolised in the liver and excreted in bile.

Erythromycin

    • Use with caution in liver impairment.
    • Erythromycin is excreted principally in the liver

Fluconazole

    •  Administer with caution to patients with liver dysfunction.
    •  Patients who develop abnormal liver function tests during fluconazole therapy must be monitored closely for the development of more serious hepatic injury.
    • Patient should be informed of suggestive symptoms of serious hepatic effect (asthenia, anorexia, persistent nausea, vomiting and jaundice).

Rifampicin

    • A daily dose of 8mg/kg should not be exceeded in patients with impaired liver function.
    • Monitor liver function weekly for 2 weeks then every 2 weeks for the next 6 weeks.
    • Eliminated in bile.


















 

References:

North-Lewis P. Drugs and the Liver. London: Pharmaceutical Press; 2008.

UK Medicines Information. Medicines Q&A ‘What is the Child-Pugh score?’2012