10th July 2026

Prescribing in patients with liver impairment

In patients with hepatic impairment, adjusting drug doses is crucial as the liver performs a vital role in drug metabolism. Impaired liver function can alter the drug metabolism, affecting the pharmacokinetics and pharmacodynamics of medications. 

Pharmacokinetic alterations in hepatic impairment

Absorption 

• In patients with hepatic impairment, it is important to consider whether a drug is lipid-soluble. Lipid-soluble drugs, e.g. propranolol may be less well absorbed in a patient with cholestasis, as they rely on bile salts to aid their absorption. This can result in reduced concentrations of the drug in the plasma and, therefore, reduced efficacy. 
• In patients with cirrhosis and ascites, the absorption of some drugs, e.g. furosemide, is delayed. 
• In portal hypertension, there is a decreased first-pass metabolism. First pass metabolism creates a high extraction ratio, which reduces bioavailability. 

Distribution 

• In patients with hepatic impairment, it is important to consider whether a drug is water-soluble, as it may distribute into the ascitic fluid, which can reduce the drug concentration, as the drug distributes into the ascitic fluid, leading to lower blood concentrations. Larger loading doses may therefore be required. 
• Chronic liver disease can also result in low albumin levels. Drugs which are largely protein-bound, e.g. phenytoin and prednisolone are affected by hypoalbuminaemia, as the proportion of unbound drug increases, resulting in potentially increased adverse effects. 

Metabolism 

• Liver disease can reduce the capacity of the liver to metabolise certain drugs, leading to toxicity. This can be caused by a reduction in the metabolic capacity of the liver (i.e. reducing hepatic cell mass due to cirrhosis) and changes in liver blood flow. Reduced hepatic metabolism of drugs is most likely to be significant in patients with decompensated cirrhosis, cholestasis, and acute liver failure, but often restricted to patients with severe disease. 
• Drugs which have a high first-pass metabolism (high extraction ratio) are particularly problematic. Advanced cirrhosis can lead to the development of varices (collateral circulation) between the portal and venous system. This can subsequently increase the proportion of absorbed oral drug entering systemic circulation, as they are metabolised less. This increases bioavailability and the potential for adverse effects. Doses of these drugs need to be reduced. 
• If the drug is a pro-drug and requires liver activation, poor liver metabolism can reduce the rate of activation and therapeutic effect of these drugs. 
• The hepatic reserve is large, and liver disease must be severe before drug metabolism is affected. 
• Whilst impaired metabolism can be indicated by a high INR (international normalised ratio), reduced albumin level, and encephalopathy, unlike renal impairment, it is not possible to predict an individual’s capacity for drug metabolism depending on liver function tests. 

Excretion 

• In cholestatic patients, the elimination of drugs through the biliary route can be reduced, resulting in accumulation. Drugs which undergo significant biliary excretion, e.g. rifampicin and fusidic acid would be particularly affected. 
• Renal impairment can occur as a result of liver disease, and if the drug is renally excreted, dose reduction may be required. 

• Drugs which cause constipation, sedation or hypokalaemia are contraindicated in severe liver disease as these can further impair cerebral function and cause encephalopathy. 
• Drugs which cause fluid retention, e.g. non-steroidal anti-inflammatory drugs and corticosteroids can worsen ascites by causing fluid retention and should be avoided in these patients. 
• Reduced hepatic synthesis of blood clotting factors, causing a prolonged prothrombin time, increases the sensitivity to oral anticoagulants, e.g. warfarin and phenindione.

Hepatotoxic drugs 

Hepatotoxicity can be idiosyncratic or dose-related. Certain drugs which can cause idiosyncratic reactions may do so more often in patients with impaired liver disease.  

Likewise, some drugs which cause dose-related toxicity may also have more of a propensity to do so in the presence of impaired liver disease. It is vital that these are used with caution in liver disease. 

Specific drug modifications for hepatic impairment

Anticoagulants:

• Warfarin may require dose adjustment, as its effect may be increased due to a reduction of clotting factors being produced by the liver. Monitoring of International Normalised Ratio (INR) is important.

Analgesics:

• Opiates can precipitate encephalopathy.
• Aspirin and NSAIDs can increase the risk of bleeding due to the reduction in clotting factors. NSAIDs can also increase ascites and should be used cautiously.
• Opioids may need dose adjustments due to altered metabolism.  
• Paracetamol should be used with caution.

Antibiotics:

• Some antibiotics, such as erythromycin, clarithromycin, and co-amoxiclav, should be used with caution and may require dose adjustment. 

Antifungals:

• Azole antifungals, like ketoconazole, should be avoided.

Antidepressants and Antipsychotics:

• Tricyclic antidepressants should be used with caution and avoided in severe impairment.
• Selective serotonin reuptake inhibitors (SSRIs) have a prolonged half-life. Doses should be reduced, or dose intervals increased. 

Cardiovascular Medications:

• Beta-blockers, calcium channel blockers, and other cardiovascular medications should be used with caution and may need dose adjustment.
• Statins may need dose adjustments. If the liver transaminases are more than 3 times the upper limit of normal, statin therapy should not be commenced or should be discontinued if already established on treatment. 

Diuretics:

• Hypokalaemia induced by loop diuretics may precipitate hepatic encephalopathy and coma—potassium-sparing diuretics can be used to prevent this.
• Diuretics can increase the risk of hypomagnesaemia in alcoholic cirrhosis, leading to arrhythmias.

Hypoglycaemic Agents:

• Insulin requirements may be decreased in hepatic impairment. 

Some oral hypoglycaemics should be avoided in hepatic impairment:

• There is an increased risk of lactic acidosis with metformin; withdraw if tissue hypoxia likely.
• Increased risk of hypoglycaemia in sulphonylureas.
• Increased risk of hepatotoxicity with glitazones. 

Immunosuppressants:

• Tacrolimus and ciclosporin, commonly used as immunosuppressants, may require dose modification.

Antivirals:

• Some antiviral medications, e.g. nucleoside reverse transcriptase inhibitors, may require dose adjustment. They should be used with caution in HCV and HBV cirrhosis.
• Antivirals should be avoided in Child-Pugh class C due to risk of severe complications.