Is Dilaudid (hydromorphone) contraindicated in patients with acute renal failure?

Hydromorphone (Dilaudid) in Acute Renal Failure

Hydromorphone is not contraindicated in acute renal failure, but requires significant dose adjustment and careful monitoring due to altered pharmacokinetics and increased risk of adverse effects in renal impairment. 1

Pharmacokinetics in Renal Impairment

• After oral administration of hydromorphone, exposure (Cmax and AUC) increases 2-fold in moderate renal impairment (CLcr = 40-60 mL/min) and 3-fold in severe renal impairment (CLcr < 30 mL/min) compared to normal renal function 1
• In patients with severe renal impairment, hydromorphone has a prolonged terminal elimination half-life (40 hours vs 15 hours in normal renal function) 1
• Only a small amount of hydromorphone is excreted unchanged in urine, with most of the dose excreted as hydromorphone-3-glucuronide (H3G) 1

Dosing Recommendations

• Patients with moderate renal impairment should be started on a lower dose of hydromorphone 1
• Patients with severe renal impairment (including acute renal failure) should be started on an even lower dose 1
• All patients with renal impairment should be closely monitored during dose titration 1

Risk of Adverse Effects

• Accumulation of hydromorphone-3-glucuronide (H3G) in renal impairment can potentially lead to neuroexcitatory effects 2
• Studies have shown that H3G levels in patients with renal insufficiency are 4 times higher than in those with normal renal function 2
• Neuroexcitatory effects observed with increasing dose or duration of hydromorphone in renal impairment include:
  • Tremor (20% prevalence) 2
  • Myoclonus (20% prevalence) 2
  • Agitation (48% prevalence) 2
  • Cognitive dysfunction (39% prevalence) 2

Clinical Decision Making

• Drug selection in acute kidney disease should be guided by the functional phase, trajectory, and stage of AKD 3
• Consider the following when selecting medications in renal impairment:
  • Renal versus non-renal excretion 3
  • Potential for nephrotoxicity 3
  • Effect of AKD on metabolites 3
  • Urgency for use of the drug 3
  • Availability of suitable alternatives 3

Alternative Opioid Options

• The American Society of Nephrology recommends opioids with no active metabolites, such as fentanyl, sufentanil, and methadone, for patients with renal insufficiency 4
• Morphine and codeine should be avoided in renal failure/dialysis patients due to accumulation of active metabolites 5
• Methadone and fentanyl appear to be safer options in renal failure 5

Monitoring Recommendations

• Patients with renal impairment receiving hydromorphone should be monitored for:
  • Signs of opioid toxicity 4
  • Neuroexcitatory effects (tremor, myoclonus, agitation, cognitive dysfunction) 2
  • Changes in renal function that may necessitate further dose adjustments 1

Clinical Pitfalls to Avoid

• Avoid using standard dosing of hydromorphone in renal impairment, as this can lead to drug accumulation and toxicity 1
• Be cautious with prolonged use of hydromorphone in renal impairment, as neuroexcitatory effects increase with duration of therapy 2
• Do not administer multiple nephrotoxic medications concomitantly with hydromorphone when possible, as this may worsen renal function 3
• Have naloxone available for patients with renal impairment receiving opioids due to higher risk of toxicity 4