Is oxycodone (opioid) renally cleared in patients with impaired renal function?

From the Guidelines

Oxycodone should be used with caution in patients with impaired renal function as it requires dose adjustment. While oxycodone is primarily metabolized by the liver, approximately 19% of the drug is excreted unchanged through the kidneys, and its metabolites are also renally cleared [ 1 ]. In patients with renal impairment, these metabolites can accumulate, potentially leading to increased side effects and toxicity.

Key Considerations

• For patients with mild to moderate renal impairment (creatinine clearance 30-60 mL/min), start with 50-75% of the normal dose.
• In severe renal impairment (creatinine clearance <30 mL/min), begin with 25-50% of the normal dose and titrate slowly based on response and side effects.
• Monitor these patients closely for signs of opioid toxicity including excessive sedation, respiratory depression, and confusion.
• Extended-release formulations should be used with particular caution in renal impairment.
• Alternative analgesics like fentanyl or hydromorphone may be preferred in end-stage renal disease as they have fewer active metabolites dependent on renal clearance [ 1 ].

Clinical Guidance

Always assess pain control and side effects frequently when using oxycodone in renally impaired patients to ensure safe and effective pain management [ 1 ].

From the FDA Drug Label

Oxycodone and its metabolites are excreted primarily via the kidney The amounts measured in the urine have been reported as follows: free oxycodone up to 19%; conjugated oxycodone up to 50%; free oxymorphone 0%; conjugated oxymorphone ≤ 14%; both free and conjugated noroxycodone have been found in the urine but not quantified. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function [see Use in Specific Populations (8.7)] . Because oxycodone is known to be substantially excreted by the kidney, its clearance may decrease in patients with renal impairment.

Oxycodone is renally cleared. Patients with impaired renal function may have a decreased clearance of oxycodone, which can increase the risk of adverse reactions.

• Key points to consider:
  • Initiate therapy with a lower than usual dosage of oxycodone hydrochloride tablets
  • Titrate carefully
  • Monitor closely for adverse events such as respiratory depression, sedation, and hypotension 2 2

From the Research

Oxycodone Renal Clearance

• Oxycodone is partially renally cleared, with most of the drug being metabolized in the liver and the rest excreted by the kidney along with its metabolites 3.
• In patients with impaired renal function, the elimination of oxycodone is impaired, leading to increased plasma concentrations and potential toxicity 4, 5.
• Studies have shown that oxycodone can be used safely in patients with renal impairment, but with caution and in reduced doses 6, 5.
• Haemodialysis can remove approximately 10% of the administered dose of oxycodone, predominantly as unconjugated oxycodone and noroxycodone or conjugated oxymorphone and noroxymorphone 5.

Clinical Implications

• Patients with mild to severe low glomerular filtration rate (GFR) may experience increased symptoms and adverse effects, such as constipation and loss of appetite, when treated with morphine, but not with oxycodone or fentanyl 7.
• The pharmacokinetics of oxycodone in patients with end-stage renal disease (ESRD) indicate that oxycodone can be used at usual doses in patients requiring dialysis, with a relatively short half-life and absence of unconjugated active metabolites 5.
• However, it is essential to monitor patients with impaired renal function closely and adjust the dose of oxycodone accordingly to minimize the risk of toxicity 6, 4, 5.