Table 2.

Clinical Use of Opioids for Chronic Pain Management in CKD and HD Patients28,30,39

Opioid	Route of Administration	Starting Dosage	Indications	Clinical Use in CKD30	Dializability and Clinical Use in HD28, 39
Buprenorphine	Transdermal patch 7 days 4 days	5–20 mcg/h ≥ 35 mcg/h	Severe chronic pain	Safer profile. No dosage adjustment required at any stage of CKD.	Not removed by HD. No dosage adjustment required.
Fentanyl citrate	Transdermal patch 3 days	≥12 mcg/h	Severe chronic pain	Safer profile. No clinically significant accumulation in CKD.	PK characteristics do not favor removal by HD. Clearance depends on filter, flow rate and type of dialysis. It could be absorbed by CT190 dialysis membranes.
Hydromorphone hydrochloride	Oral	≥4 mg OD	Severe chronic pain (second line treatment)	Use with caution, with close monitoring. Dose adjustment required in renal failure*: Mild: 100% normal dose Moderate: 50% normal dose Severe: 25% normal dose Increase dosing intervals as needed.	H3G accumulates between dialysis treatments. Easily dialyzed: 60% removed by HD. Sudden decreases in opioid concentrations may result in withdrawal symptoms. Post-dialysis supplemental dosing could be required, but no clinical data are available.
Oxycodone hydrochloride	Oral	≥5 mg BID	Severe chronic pain (second line treatment)	Use with caution, with close monitoring. Dose adjustment required in renal failure: Mild: 50% normal dose Moderate: 25–50% normal dose Severe: contraindicated Increase dosing intervals as needed.	Oxycodone and its active metabolite, noroxycodone, are removed by HD. Oxycodone has been used in dialysis-dependent patients, and it is well-tolerated, without need for opioid compensation.
Tramadol	Oral	≥50 mg BID	Severe chronic pain (second line treatment)	Use with caution, with close monitoring. Dose adjustment required in renal failure: Mild: 100% normal dose Moderate: 50% normal dose Severe: 50% normal dose Increase dosing intervals as needed.	Significantly removed by hemodialysis. Re-dosing after a HD session may be necessary.
Tapentadol hydrochloride	Oral	≥25 mg BID	Severe chronic pain (second line treatment)	No dose adjustment required for mild to moderate renal failure. No data available for severe CKD.	Data not available in HD. It is likely to be dialyzed to some extent, because of its low protein binding, low molecular weight, and average water solubility.
Methadone	Oral	1–2 mg BID	Severe chronic pain Mainly for MMT	Use only when other opioids are contraindicated. Dose reduction may be required in ESRD because its half-life is very long and unpredictable, therefore toxicity may be delayed	Methadone and its metabolites are not removed by HD. No supplemental doses are required after a HD session. Check Q-T interval. Arrhythmias may be exacerbated by potassium and magnesium reduction after HD.
Morphine sulphate	Not recommended due to metabolites accumulation. To be avoided in CKD and HD patients.
Codeine	Not recommended due to metabolites accumulation. To be avoided in CKD and HD patients.

Notes: *Mild: Creatinine Clearance 60 to < 90 mL/min; Moderate: Creatinine Clearance 30 to < 60 mL/min; Severe: Creatinine Clearance 15 to < 30 mL/min. Green: safe use in CKD; Yellow: use with caution in CKD; Orange: not recommended in CKD.

Abbreviation: MMT, methadone maintenance treatment.