Appendix 2: Use of Opioids in Hepatic Failure
This article is Appendix 2 of the book "How Cancer Pain is Treated: A non-technical guide for patients and their carers". You will find links to the other articles in the series at the bottom of this page. Alternatively, you may download the whole book in various formats HERE. (All downloads are free.)
This article, written by a senior medical practitioner with considerable experience in palliative medicine and hospice care, is offered purely for educational purposes. Nothing in it should be taken as therapeutic advice for any particular patient. Mention of any trade (brand) name should not be taken as an endorsement of the brand or its manufacturer.
If you read the articles in this series carefully, and think about the information in them, in relation to a particular pain management problem affecting you or someone you love, you may sometimes be able to think of modifications to the current treatment which might be expected to improve the situation.
However, it is very dangerous to make changes to a patient's medication without first discussing them with the prescribing doctor. The doctor must always know exactly what the patient is taking, as virtually all medications can cause unwanted side effects and interact in various ways with other medications.
Importantly, this also applies to "natural", "alternative" or "complementary" therapies, many of which have significant interactions with prescribed medications. Therefore, even if you feel that the current pain management is not optimal, never make any changes without first discussing them with the doctor.
It is not uncommon for patients who need opioid analgesia to also have some degree of liver failure, either as a result of cancer in the liver or because of some other illness affecting it. As most opioids are removed from the body chiefly by being metabolised in the liver, an increased amount of the parent drug, and a decreased concentration of its metabolites (which sometimes provide part of the analgesic effect), is the usual result when hepatic function is significantly reduced. (Fentanyl is an exception to this rule, as discussed below.)
Weak Opioids and Pethidine
As in the case of renal failure, neither weak opioids nor pethidine should be used in patients with hepatic failure, as their combination of a weak analgesic effect and plentiful, sometimes serious, side effects leaves very little room for manoeuvre. Other opioids vary in their suitability for patients with hepatic failure, as discussed below.
Morphine, Oxycodone and Hydromorphone
Morphine, oxycodone and hydromorphone can usually be used cautiously in hepatic failure by means of downward adjustment of the dose and/or upward adjustment of the interval between doses. However, dosage adjustment can be expected to become more difficult as liver function deteriorates further.
Although fentanyl is metabolised in the liver, its metabolism appears to require very little residual liver function. Markedly reduced hepatic blood flow can interfere with the metabolism of fentanyl, but hepatic failure itself rarely results in fentanyl accumulation. For this reason, fentanyl, which is usually the opioid of choice in the presence of renal failure, is also, in most cases, the opioid of choice when hepatic failure is severe enough to preclude the safe and effective use of morphine, oxycodone or hydromorphone. In many cases, it is not even necessary to use reduced doses of fentanyl in the presence of hepatic failure, but, of course, this should not discourage frequent review of the patient's response.
Buprenorphine is metabolised in the liver, and its metabolites are excreted into the bile. (They are also, to a lesser extent, excreted by the kidneys.) There are some reports of acute liver toxicity associated with buprenorphine in the presence of liver disease, but information about its use in this situation is otherwise quite sparse. At the time of writing, I would suggest that buprenorphine, if it is ever used at all, should not be used in the presence of significant liver disease unless all other strong opioids are contra-indicated.
Methadone, which is very difficult to use safely at the best of times, should not be used in the presence of significant hepatic failure unless absolutely no alternative exists. This is simply because the risk of excessive blood levels of methadone developing will be greater, and more unpredictable, than ever.
Declaration of Interest
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Footnote: (Click the number of the footnote to return to its reference in the text)
 This may be particularly important in the case of codeine, and possibly also dihydrocodeine, as some of their hepatic metabolites (especially morphine, in the case of codeine) may contribute significantly to their analgesic effect. However, the metabolism of codeine and dihydrocodeine remains very incompletely understood at the time of writing.
Articles in the Cancer Pain Series
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