Which opioids are contraindicated in patients with End-Stage Renal Disease (ESRD)?

Opioids Contraindicated in End-Stage Renal Disease

Avoid meperidine, codeine, morphine, tramadol, and tapentadol in patients with ESRD due to accumulation of toxic metabolites that cause neurotoxicity, seizures, and respiratory depression. 1

Opioids That Must Be Avoided

Absolutely Contraindicated

• Meperidine (Demerol): Accumulation of normeperidine causes neurotoxicity, seizures, and has poor analgesic efficacy 1, 2
• Codeine: Produces toxic metabolites that accumulate in renal failure and is contraindicated in ESRD 1, 3, 4
• Morphine: Morphine-6-glucuronide (active) and morphine-3-glucuronide (antagonist) accumulate significantly, causing opioid-induced neurotoxicity including confusion, myoclonus, and seizures 3, 4, 2

Not Recommended

• Tramadol: Not recommended in renal insufficiency (GFR <30 mL/min) and ESRD due to metabolite accumulation and increased seizure risk 1, 3, 4
• Tapentadol: Not recommended in renal insufficiency (GFR <30 mL/min) and ESRD 1

Opioids Requiring Extreme Caution (Use Only If Alternatives Unavailable)

These agents require dose reduction of 50%, extended dosing intervals, and intensive monitoring for neurotoxicity:

• Hydrocodone: Use with caution and adjust dosage in ESRD 1
• Oxycodone: Requires dose reduction and increased dosing intervals with careful titration and frequent clinical observation 1, 3
• Hydromorphone: Active metabolite (hydromorphone-3-glucuronide) accumulates between dialysis treatments, causing increased sensory-type pain and reduced analgesia duration 3, 2

Preferred Safe Opioids for ESRD

Fentanyl is the first-line opioid for ESRD patients because it undergoes hepatic metabolism with no active metabolites and minimal renal clearance 1, 3, 4, 2

Other safe alternatives include:

• Buprenorphine: Safe in chronic kidney disease stages 4-5 with predominantly hepatic excretion and no dose adjustment needed 4, 2
• Methadone: Safe due to fecal excretion with no active metabolites, but should only be administered by clinicians experienced in its use due to variable half-life and risk of QT prolongation 1, 3, 4, 2
• Sufentanil: No active metabolites, preferred for renal insufficiency 1

Critical Monitoring Requirements

Monitor all ESRD patients receiving opioids for:

• Excessive sedation and respiratory depression 3, 2
• Myoclonus, confusion, and hallucinations (signs of metabolite accumulation) 4, 2
• Hypotension 3, 2

Have naloxone immediately available for patients at higher risk of opioid toxicity, particularly those with renal impairment 3, 2

Common Pitfalls to Avoid

• Never use morphine "just this once" - even single doses cause metabolite accumulation in ESRD patients 2
• Do not assume standard dosing applies to any opioid except fentanyl, buprenorphine, and methadone 2
• Avoid combining opioids with benzodiazepines or gabapentinoids as synergistic respiratory depression is magnified in renal failure 2
• Institute bowel regimen with stimulant or osmotic laxatives prophylactically for all patients on sustained opioid therapy 3, 2