Analgesics in kidney and liver disease

In kidney failure avoid morphine and codeine, use hydromorphone or oxycodone cautiously at reduced doses, and favor fentanyl or methadone; renally dose gabapentinoids and give pregabalin a supplemental dose after hemodialysis.

1. Active metabolites drive renal risk. A review of opioid kinetics in renal failure recommends avoiding morphine and codeine, using hydromorphone or oxycodone with caution and monitoring, and notes methadone and fentanyl appear safe ¹.
2. "Safe" renal opioids are least dialyzable. Methadone and fentanyl, considered safest in renal failure, are also the least removed by dialysis ¹.
3. Hydromorphone needs a lower start. In renal or hepatic impairment, begin at one-quarter to one-half the usual starting dose depending on severity, with careful titration ².
4. Tramadol intervals lengthen. With creatinine clearance below 30 mL/min, give tramadol every 12 hours, maximum 200 mg/day; in severe hepatic impairment the dose is 50 mg every 12 hours ³.
5. Pregabalin is renally cleared. It is eliminated mainly unchanged in urine, so its daily dose is adjusted to creatinine clearance, and dialysis patients receive a supplemental dose immediately after each 4-hour hemodialysis session ⁴.
6. Count kidney and liver disease as opioid risk factors. CDC asks clinicians to consider renal or hepatic insufficiency, with sleep apnea, pregnancy and mental health or substance use disorders, when assessing opioid risk ⁵.

Codeine is metabolized to morphine, so it shares morphine's renal risk; neither belongs in a dialysis regimen, and switching to fentanyl or methadone is the safer direction ¹.

• Only about 7% of a tramadol dose is removed by hemodialysis, so dialysis patients can take their regular dose on dialysis day ³.
• Dialysis does not help much in tramadol overdose because so little drug is removed ³.
• Hepatic impairment raises hydromorphone exposure, the reason for the reduced start ².
• Hydrocodone levels rise in renal and hepatic impairment; start low ⁶.
• Pregabalin at creatinine clearance 30–60 mL/min is 75–300 mg/day; below 15 mL/min, 25–75 mg/day ⁴.
• Celecoxib dose is halved in moderate hepatic impairment (Child-Pugh B) and not recommended in severe hepatic impairment ⁷.
• Avoid celecoxib in advanced renal disease unless benefit outweighs the risk of worsening renal function ⁷.
• CDC advises weighing NSAID risks carefully with renal insufficiency, hypertension or heart failure ⁵.

• Choosing morphine or codeine for a dialysis patient ¹.
• Skipping pregabalin on dialysis days instead of dosing after dialysis ⁴.
• Giving the usual hydromorphone starting dose in hepatic or renal impairment ².
• Reducing tramadol on dialysis days; little is removed, so the regular dose is given ³.