A very important topic with regards to opioid therapy is the special considerations of patients who develop liver and renal (i.e. kidney) dysfunction. Although chronic opioid therapy has minimal long-term effects on organs, organ dysfunction can have a dramatic effect on side effects from these medications.

As in any clinical setting, the ‘right dose’ of an opioid analgesic medication is that which provides adequate pain relief in conjunction with an acceptable side effect profile.

It is important to monitor renal and liver function in patients taking chronic opioids and before starting opioid therapy. Renal or hepatic impairments can lead to toxicity as most opioids are metabolized in the liver and excreted through the renal system. We recommend that you get annual liver and renal function tests and inform all your physicians if there are any abnormal results.

Hepatic Failure
In hepatic failure, opioid clearance is reduced and drug bioavailability is increased. These changes can be secondary to reduced hepatic blood flow (limiting first-pass metabolism) and/or decreased CYP450 enzyme levels in these patients. It is recommended that if used, opioid dosing should be reduced to 50% of the recommended starting doses in these patients. Morphine, oxycodone, hydromorphone and tramadol 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.

Methadone, codeine and meperidine should be avoided entirely in patients with liver failure. Codeine is a prodrug that is hepatically converted to morphine by the liver. In patients with liver dysfunction, pain control can be compromised if codeine is not metabolized. Meperidine is metabolized by liver to normeperidine. In hepatic disease, meperidine clearance is reduced and its half-life is prolonged. Seizures, a major side effect of meperidine and normeperidine, can occur at reduced doses in patients with hepatic failure. Methadone 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.