Pain Management

For opioids, start with a low dose immediate release preparation and titrate slowly according to response and side effects. Regular review is essential with careful monitoring for signs of toxicity and prevention of constipation. Once established on immediate release opioids, the dose can then be converted to slow release preparations or transdermal patches. When transdermal patches are being considered, fentanyl should be used in preference to other opioids.

Analgesics: recommendations based on type of liver disease

Mild hepatitis without cirrhosis

Paracetamol: Normal therapeutic doses (caution in malnourished or acute viral hepatitis)

NSAID: Normal doses

Opioid: Normal therapeutic doses

Cholestasis

Paracetamol: Normal therapeutic doses

NSAID: Avoid if possible. If necessary, ibuprofen may be best option

Opioid: Use with caution. Monitor for adverse effects. May worsen pruritus

Compensated cirrhosis

Paracetamol: Normal therapeutic doses (caution in malnourished and chronic alcoholics)

NSAID: Avoid

Opioid: Avoid where possible.

Weak opioids: Dihydrocodeine may be preferred compared to codeine.

Preferred strong opioid: Morphine. Use small doses with reduced frequency of administration

Decompensated cirrhosis

Paracetamol: Normal dose with caution. Half-life may be prolonged

NSAID: Avoid

Opioid: As for compensated cirrhosis but greater caution needed as increased accumulation likely

Acute liver failure

Paracetamol: Extend dose interval

NSAID: Avoid

Opioid: As for compensated cirrhosis. Strong opioids preferably only considered after discussion with liver unit.

Recommendations on the use of analgesics in liver disease

Paracetamol

Class: Non-opioid

Recommendations in liver disease: Use with caution

Comments: Can opt for a sub-maximal dose 500mg -1g TDS-QDS especially if at higher risk for paracetamol toxicity *

* Some patients may be at increased risk of experiencing paracetamol toxicity at therapeutic doses, particularly those with a body-weight under 50kg and those with risk factors for hepatotoxicity.  Clinical judgement should be used to adjust the dose of oral and intravenous paracetamol in these patients. 

Codeine

Class: Weak opioid

Recommendations in liver disease: Avoid use

Dihydrocodeine

Class: Weak opioid

Recommendations in liver disease: Use with caution

Tramadol

Class: Weak opioid

Recommendations in liver disease: Avoid if severe

Comments: Moderate impairment – increase dosing interval

Tapentadol

Class: Strong Opioid and NARI

Recommendations in liver disease: Avoid if severe

Comments: Immediate-release tablets, initial max. daily dose 150 mg; for modified-release tablets, initial max. daily dose 50 mg

Morphine

Class: Strong Opioid

Recommendations in liver disease: Use with caution

Comments: Moderate impairment – use lower doses

Severe impairment – lower doses and extend dosing interval

Diamorphine

Class: Strong Opioid

Recommendations in liver disease: Use with caution

Comments: Moderate impairment – use lower doses

Severe impairment – lower doses and extend dosing interval

Buprenorphine

Class: Strong Opioid

Recommendations in liver disease: Use with caution

Comments: May be opioid of choice in hepatorenal syndrome

Oxycodone

Class: Strong Opioid

Recommendations in liver disease: Contra-indicated moderate to severe liver disease

Comments: Moderate impairment – lower doses; minimum dosing interval of 6 hourly for immediate release products

Targinact® oxycodone/naloxone

Class: Strong Opioid

Recommendations in liver disease: Contra-indicated moderate to severe liver disease.
Naloxone – Avoid in liver disease

Comments: Naloxone component may be systemically absorbed resulting in opioid withdrawal and thus precipitate pain

Fentanyl

Class: Strong Opioid

Recommendations in liver disease: Use with caution

Comments: Avoid transdermal products when initiating opioids.

Single doses appear unaltered by liver disease.

May be suitable for treatment of breakthrough pain

Hydromorphone

Class: Strong Opioid

Recommendations in liver disease: Use with caution

Comments: Dosage reduction necessary

Alfentanil

Class: Strong Opioid

Recommendations in liver disease: Use with caution

Comments: Dosage reduction necessary

Methadone

Class: Strong Opioid

Recommendations in liver disease: Seek specialist advice

Comments: Seek specialist advice

NSAIDs

Class: Adjuvant

Recommendations in liver disease: Avoid

Amitriptyline

Class: Adjuvant

Recommendations in liver disease: Use with caution

Comments: Avoid in severe liver disease

Pregabalin

Class: Adjuvant

Recommendations in liver disease: Not affected by liver impairment

Comments: Normal doses can be used

Ketamine

Class: Adjuvant

Recommendations in liver disease: Use with caution

Comments: Dosage reduction necessary

Gabapentin

Class: Adjuvant

Recommendations in liver disease: Not affected by liver impairment

Comments: Normal doses can be used

Co-administration of enzyme inducing antiepileptic medications may increase paracetamol toxicity – doses should be reduced. 

DISCLAIMER

This Guide is intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.
Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.
While WMPCPS takes every care to compile accurate information , we cannot guarantee its correctness and completeness and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.