Is oxycodone (OxyContin) safer than hydromorphone (Dilaudid) in patients with end-stage renal disease (ESRD)?

From the Guidelines

Oxycodone is generally safer than hydromorphone for patients with end-stage renal disease (ESRD). In ESRD, oxycodone has fewer active metabolites that accumulate compared to hydromorphone, which can lead to a more predictable effect and potentially fewer adverse outcomes. When using oxycodone in ESRD patients, start with a reduced dose (about 25-50% of the normal starting dose) and extend the dosing interval to account for decreased clearance. Careful monitoring for signs of opioid toxicity such as excessive sedation, respiratory depression, or confusion is essential. Dose adjustments should be made gradually based on patient response. The reason oxycodone is preferred is that while both medications are eliminated primarily by the liver, hydromorphone's metabolites are more dependent on renal clearance and can accumulate in ESRD, potentially causing prolonged or unpredictable effects. However, all opioids should be used cautiously in ESRD, with close monitoring and consideration of alternative pain management strategies when appropriate.

Some key points to consider when using opioids in ESRD patients include:

• Avoiding opioids with active metabolites that can accumulate in renal failure, such as morphine and codeine 1
• Using opioids with no active metabolites, such as fentanyl and methadone, which are preferred in patients with renal insufficiency or ESRD 1
• Carefully titrating and frequently monitoring opioids primarily eliminated in urine, such as fentanyl, oxycodone, and hydromorphone, for risk of accumulation of the parent drug or active metabolites 1
• Performing more frequent clinical observation and opioid dose adjustment in patients with renal or hepatic impairment who receive opioids 1

It's also important to note that methadone can be a good alternative in patients with significant renal function impairment, but it should only be used by experienced clinicians 1. Overall, the use of opioids in ESRD patients requires careful consideration and monitoring to minimize the risk of adverse outcomes. The most recent and highest quality study recommends using methadone or opioids with no active metabolites in patients with renal impairment, and carefully titrating and monitoring opioids primarily eliminated in urine 1.

From the FDA Drug Label

Oxycodone 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. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Initiate therapy with a lower than usual dosage of oxycodone hydrochloride tablets and titrate carefully. Monitor closely for adverse events such as respiratory depression, sedation, and hypotension [see Clinical Pharmacology (12.3)] .

After oral administration of a single 4 mg dose (2 mg hydromorphone immediate-release tablets), exposure to hydromorphone (C max and AUC 0-48) is increased in patients with impaired renal function by 2-fold in moderate (CLcr = 40 to 60 mL/min) and 3-fold in severe (CLcr < 30 mL/min) renal impairment compared with normal subjects (CLcr > 80 mL/min)

In addition, in patients with severe renal impairment hydromorphone appeared to be more slowly eliminated with longer terminal elimination half-life (40 hr) compared to patients with normal renal function (15 hr). Patients with moderate renal impairment should be started on a lower dose. Starting doses for patients with severe renal impairment should be even lower

Patients with renal impairment should be closely monitored during dose titration [see Use in Specific Populations ( 8. 7)].

Comparison of Safety in End-Stage Renal Disease (ESRD)

• Both oxycodone and hydromorphone require dose adjustments in patients with renal impairment.
• Hydromorphone is increased by 2-fold in moderate and 3-fold in severe renal impairment, and has a longer terminal elimination half-life in severe renal impairment.
• Oxycodone requires careful dose selection and monitoring of renal function in patients with decreased renal function.
• Neither drug is safer than the other in ESRD, as both require careful dose titration and monitoring. 2 3

From the Research

Comparison of Oxycodone and Hydromorphone in End-Stage Renal Disease (ESRD)

• Both oxycodone and hydromorphone are used for pain management in patients with ESRD, but their safety profiles differ due to varying pharmacokinetics and metabolite accumulation [(4,5)].
• Oxycodone is considered safer than hydromorphone in ESRD patients due to its relatively shorter half-life and lower risk of toxic metabolite accumulation [(6,7)].
• Hydromorphone, on the other hand, has limited evidence supporting its use in ESRD patients, and its metabolites may accumulate to toxic levels 4.

Pharmacokinetics and Metabolism

• Oxycodone undergoes significant removal during hemodialysis, with approximately 10% of the administered dose removed 7.
• The pharmacokinetics of oxycodone in ESRD patients are characterized by a relatively short half-life, which is further reduced during hemodialysis [(6,7)].
• Hydromorphone's pharmacokinetics in ESRD patients are not as well-studied, but its use is generally cautioned due to the potential for toxic metabolite accumulation [(4,5)].

Clinical Recommendations

• Oxycodone can be used at usual doses in patients requiring dialysis, but careful monitoring is necessary [(7,5)].
• Hydromorphone should be used with caution in ESRD patients, and alternative opioids such as buprenorphine or fentanyl may be preferred [(4,8,5)].
• Accurate pain diagnosis, opioid titration, and tailoring are essential to minimize risks and improve outcomes in ESRD patients 5.