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Opioid elimination

In this article Dr Victoria Hewitt describes opioid elimination from the body and explains why it is important prescribers are aware of this.
© Newcastle University
Almost all opioids and their associated metabolites are excreted renally. The effect of renal function on the elimination of an opioid differs between individuals and the opioid concerned. If kidney function is impaired, elimination of the parent compound and its metabolites is altered meaning careful dosing and close monitoring of the patient is warranted.


The main metabolites of morphine – morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) – cross the blood-brain barrier, causing central neurological effects. Both accumulate in renal failure. The half life of M6G, for instance, is normally just over 2 hours. In the presence of renal failure this can increase up to 10 fold.

Codeine and diamorphine

These drugs are metabolised to morphine and eliminated accordingly. For codeine, the active metabolite codeine-6-glucuronide is also excreted renally.


As with morphine, oxycodone and its metabolites accumulate in renal failure. Although oxymorphone is the only clinically significant metabolite in humans, it is considerably more potent than the parent drug and toxicity can occur. Nevertheless, oxycodone is the opioid of choice in many renal units in the presence of mild to moderate renal failure. In these circumstances it is used cautiously and initiated at lower doses.


Hydromorphone-3-glucuronide (H3G), the main metabolite of hydromorphone, accumulates up to 4 times its normal plasma level. Accumulation of H3G causes neuro-excitation and cognitive impairment.

Fentanyl and alfentanil

These drugs are excreted by the kidneys but as their metabolites are inactive and non-toxic in humans they are considered safe in renal failure.


Methadone is excreted into the GI tract not the kidneys, so is safe in renal failure. Drug elimination, however, is reduced by if the patient is constipated.
© Newcastle University
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