Moderate to severe chronic pain is common in chronic kidney disease and impact 50% of hemodialysis patients. The pharmacokinetics of opioids is complex in renal failure; still, with their appropriate selection and titration, patients with renal failure can achieve analgesia with minimal adverse effects.

Not recommended for use:
• Meperidine: may cause seizures due to accumulation of normeperidine.
• Codeine: can cause profound toxicity that can be delayed and may occur after small doses. It should be avoided in patients with a Glomerular Filtration Rate (GFR) <30 mL/min.
• Dextropropoxyphene: can cause central nervous system and cardiac toxicity.
• Morphine and hydromorphone: both have 3-glucuronide metabolites that accumulate and may case neurotoxicity, so these should be used with caution for chronic use when GFR is <30 mL/min.

Use with caution:
• Oxycodone: its metabolites do not appear to be as associated with clinically-significant neurotoxicity. Titration and careful monitoring are needed.

Less associated risk:
• Fentanyl: is relatively safe as it has no active metabolites. Titration and close monitoring for sedation are needed.
• Methadone: is relatively safe as it has no active metabolites and limited plasma accumulation due to enhanced elimination in the feces.
• Buprenorphine: may be a good option in renal failure due to lack of active metabolites or accumulation of parent compound. Titration and careful monitoring are needed.

It is difficult to promote specific opioid dosing algorithms.
• Methadone and buprenorphine likely do not require dose adjustment.
• It is suggested to decrease the dose of morphine, oxycodone, or hydromorphone by 25% if creatinine clearance is 10-50 mL/min and 50% if creatinine clearance is <10mL/min.
• It is suggested to focus on PRN opioid dosing that adequately relieves pain without unacceptable side effects, and to use caution with scheduled dosing.

Many opioids can be used with titration and careful monitoring when GFR is <50; this should not impede the effective use of opioids in these patients.
A multimodal approach to pain therapy should be considered. This may involve: acetaminophen, nortriptyline, renally-dosed gabapentin or pregabalin, corticosteroids, tizanidine, interventional therapies, and physical therapy.

See reference for more information.

Adapted from Arnold R, Verrico P, Kamell A, Davidson SN. Opioid use in renal failure. Palliative Care Network of Wisconsin. Fast facts and concepts #161. Internet. Available at https://www.mypcnow.org/fast-fact/opioid-use-in-renal-failure/ Accessed on June 5, 2020.