Prescribing in Liver Impairment
There is no single marker for quantifying liver impairment (unlike renal excretion).
Drug metabolism is decreased in severe liver disease.
General Advice
For general advice, see Individualising Drug Therapy, including: when prescribing ‘start low and go slow’; consider dose tapering after desired effects are achieved and discontinue unnecessary drugs.
Drug metabolism varies substantially between individuals.
There are several causes of decreased drug metabolism:
- Irreversible:
- Genetics – there is wide variability between individuals, only partly identified by individual genetic tests.
- Age – drug metabolism decreases with age, at a rate of 1% per year after the age of forty.
- Frailty – associated with decreased drug metabolism over and above the decrease associated with age.
- Organ failure has been shown to reduce drug metabolism.
- Liver disease – affects drug clearance only when severe (Child Pugh B or C).
- Renal dysfunction – end-stage renal disease is associated with approximately 50% reduction in drug metabolism.
- COPD – severe COPD is associated with approximately 50% reduction in drug metabolism.
- Heart failure – the chronic effects are not quantified, but acute hepatic congestion decreased drug metabolism.
- Reversible:
- Enzyme inhibition by drugs.
- Acute illness: hypo-perfusion and metabolic insult (e.g. acidosis)
Assessing metabolic function:
- Drug metabolism is decreased in "severe" liver dysfunction (Child Pugh B or C).
- There is no single marker for liver function (and therefore liver drug metabolism).
- Clotting factors and albumin are useful surrogate markers of liver synthetic function. Note: tranaminases (ALT, AST, etc) do not reflect drug metabolism.
Pharmacokinetic Considerations
- Approximately 70% of drugs are cleared predominantly by metabolism, mostly in the liver.
- Predicting doses for individuals is hard and doses are usually titrated to response (clinical or laboratory).
- The patient's dose requirements for other drugs metabolised by the same pathway provides some information. For example, bradycardia with moderate doses of metoprolol should prompt caution with other CYP2D6 substrates.
- In severe liver disease reduce starting doses by 50%.
Common narrow therapeutic index drugs relevant in liver impairment (not exhaustive):
- anti-arrhythmics
- anticoagulants
- antiepileptics
- antipsychotics
- benzodiazepines
- immunosuppressants
- NSAIDs
- opioids
- paracetamol
For specialist advice about using a specific medicine contact the relevant specialty, or Medicines Information (ext 80900).
Pharmacodynamic Considerations
- Sensitivity to some drugs may be increased e.g. CNS agents (because encephalopathy may accompany severe liver disease) and anticoagulants (because clotting factors may be altered).
- Some medicines are hepatotoxic. If you are investigating a patient with possible drug-induced liver injury (DILI), refer to Livertox, or contact Medicines Information (ext 80900).
Topic Code: 93228
