Basic Principles of Prescribing Analgesia in Patients with Hepatic Impairment

Unlike renal dysfunction there are no current website resources giving drug specific guidelines on doses for analgesics or other medicines in liver disease as the patient factors are so variable.  The following gives general guidance, but for specific drugs check with your hospital’s specialist gastroenterology pharmacist (OUH bleep 1084/6146) or medicines information department (OUH extension 21505).

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Guidelines for drug use in hepatic impairment

  • The following factors should be considered when deciding an optimum drug treatment for a patient with liver disease:
    • Type, extent and severity of liver disease
    • Pharmacokinetics and pharmacodynamics of the drug
    • Adverse reactions of the drug
    • Patient specific factors e.g. age, comorbidities, severity of the condition being treated, concomitant medications, nutrition status
  • Analgesic prescribing should be kept to a minimum – use the smallest effective doses at the greatest interval, and titrate according to clinical response. 
  • The oral route is preferred in patients with liver disease. Intramuscular injections should be avoided as they cause haematoma. 
  • Avoid sedating drugs in patients at risk of developing hepatic encephalopathy. Many of these drugs have long half-lives and are metabolised by the liver so their duration and intensity of action may be prolonged. The brain also becomes more sensitive to sedating effects in liver disease. A sedative drug may precipitate or mask encephalopathy.
  • Give regular laxatives to avoid encephalopathy particularly if sedating drugs are prescribed.  
  • Avoid Oramorph in alcoholic liver disease and pancreatitis due to its 10% alcohol content.  Sevredol (short acting, immediate release morphine tablets) should be prescribed instead at the same dose and interval as Oramorph.
  • In patients with hepatic dysfunction, avoid hepatotoxic drugs where possible. Patients with existing hepatic disease are not more prone to hepatotoxicity (unless it is dose-related), but they have diminished reserve hepatic function and may suffer disproportionately if hepatotoxicity does occur. Drug hepatotoxicity causing even clinically insignificant or transient changes in LFTs on top of existing liver disease will confuse the diagnostic picture.  Many herbal remedies and illicit substances cause liver toxicity.  Most drug reactions affecting the liver occur within the first 90 days of the first dose. 
  • For drugs metabolised by the liver, be alert to signs of drug side effects, know what they are and monitor for them. Monitor drug levels where appropriate. 
  • The doses of highly protein-bound drugs may need reducing in patients with low albumin levels due to chronic liver disease. 
  • Metabolism by the liver is the main route of elimination for many drugs. Drugs that are highly dependent on the liver for deactivation or clearance are likely to need dose reduction in moderate to severe liver disease. 
  • Drugs can affect the metabolism of other drugs by inhibition or induction of CYP450 enzymes in the liver. 
  • Non-systemic treatments should be chosen where possible. Renally excreted drugs are also preferred as long as renal function is normal. Monitor for any changes in renal function which may indicate developing hepatorenal syndrome. 
  • It was previously thought that drugs that increase the risk of bleeding should be avoided or used with caution, but current understanding is that hepatic disease patients are hypercoagulable, so this is no longer felt to be a concern.  PT/APTT reflects the degree of liver damage not bleeding risk. Advanced cirrhosis (low albumin) has a greater risk. If there is active bleeding or untreated varices, drugs that can increase the risk of bleeding should be avoided.  NSAIDS should be avoided in cirrhosis.