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• Amitriptyline, bupivacaine, levobupivacaine, lignocaine, ropivacaine, clonidine,
gabapentin, codeine, hydromorphone, methadone, morphine and tramadol have been
used in patients with renal disease but depending on the degree of impairment and, in the
case of local anaesthetics, whether or not administration is prolonged, may require a
reduction in dose. Levobupivacaine, with similar clearance mechanisms, and ropivacaine
may be safer than bupivacaine because of a higher therapeutic ratio.
• NSAIDs (both nsNSAIDs and coxibs), dextropropoxyphene and pethidine should not be
used in the presence of significant renal impairment.

11.6.2 Patients with hepatic disease
Not all patients with hepatic disease have impaired liver function. In patients with hepatic
impairment, most analgesic drugs have reduced clearance and increased oral bioavailability,
but the significance of these changes in the clinical setting has not been studied in depth. The
available data indicates the following (see Table 11.6 for references).
• While there are limited data, dose adjustments are usually not required for alfentanil,
buprenorphine, fentanyl, morphine, oxycodone and sufentanil.
• Tramadol may need to be given at lower doses.
• Methadone should be used with caution in the presence of severe liver disease because of
the potential for greatly prolonged clearance.
• The clearance of local anaesthetics may be significantly impaired; doses may need to be
decreased if use is prolonged.
• Carbamazepine and valproate should be avoided in patients with severe hepatic
impairment.
• It may be wise to reduce the dose of paracetamol in patients with significant degrees of
hepatic impairment.

Key messages
The following tick box  represents conclusions based on clinical experience and expert
opinion.

 Consideration should be given to choice and dose regimen of analgesic agents in patients
with hepatic and particularly renal impairment (U).

Table 11.5 Analgesic drugs in patients with renal impairment
Drug Comments Recommendations References
NB doses must still be CHAPTER 11
titrated to effect for each
patient
Opioids
Alfentanil No active metabolites No dose adjustment Craig & Hunter,
92% protein bound; increases in required unless renal 2008
free fraction may result from failure is severe Davies et al, 1996
alterations in protein binding Mercadante &
Arcuri, 2004
Murtagh et al,
2007

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