Scenario 2 - Choice of antiemetic

Despite the manufacturers of domperidone contraindicating its use in patients with liver disease [1, 2], it is the drug of choice in many liver centres as it has minimal side effects and can be used in all liver patients. In most liver patients the initial starting dose is 10 mg three times a day for adults and 200 pg/kg three times a day for children. However, as domperidone is extensively metabolised by the liver, the initial dose in patients with severe hepatic impairment or cirrhosis should be reduced by 50%, and gradually titrated up to a maximum of 10 mg three times a day, as accumulation of the drug may occur. 

The dose of metoclopramide should be reduced by 50% in patients with cirrhosis, as reduced clearance may result in accumulation of the drug. The use of metoclopramide in patients with moderate to severe liver disease may also increase the risk of developing gynae-comastia. 

Patients with liver disease may have an increased gastrointestinal transit time [3]. These patients may benefit from taking a pro-kinetic agent, as normalisation of gastrointestinal motility will reduce the time available for the absorption of nitrogenous compounds that may precipitate encephalopathy. The use of pro-kinetic agents has also been shown to reduce intestinal bacterial overgrowth in patients with cirrhosis [4-6]. 

All 5HTj-receptor antagonists are metabolised by the liver, but, with the exception of ondansetron, no dosage adjustments are recommended for the treatment of acute nausea. However, in patients with chronic nausea the dosage of 5HTj-receptor antagonist should be reduced to prevent accumulation of the parent drug and any active (or inactive) metabolites. 

Drug Bioavailability T max Brotein binding Metabolism % excreted unchanged Half-life Active metabolites 

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