Table 3:
Possible CNS-related ADRs and pharmacokinetics changes of opioids in CKD or ESKD [110].
| Drug | ADR in CKD or ESKD | Pharmacokinetics data in CKD |
|---|---|---|
| Buprenorphine | Safer profile [31] | No dose adjustment required [31] |
| Codeine | Prolonged CNS depression | Not recommended in CKD [31] |
| Dihydrocodeine | CNS depression | N/A |
| Fentanyl | Prolonged sedation | Its clearance may be altered |
| Hydrocodone | Limited information available [111] | Metabolized to hydromorphone; caution in CKD [112] |
| Hydromorphone or active metabolite H3G | Myoclonus, mental status changes; neuro-excitatory side effects [30] | Active metabolite may accumulate in CKD [112, 113], close monitoring is required [31] |
| Meperidine | CNS depression, psychosis, hyperactivity, seizures, myoclonus, mental status changes [111] | Active metabolite excretion depends on GFR. Dose adjustment is recommended. It should be avoided in ESKD |
| Methadone | PK is unaffected but poorly removed by hemodialysis | |
| Morphine or M3G (active metabolite) | CNS depression, morphine encephalopathy, neuroexcitatory effects such as allodynia, myoclonus, and seizures, cognitive impairment [30] | Disposition or sensitivity is altered. Not recommended in CKD [31] |
| Oxycodone | Lower risk of hallucinations and mental confusion [31] | Active metabolite excretion depends on GFR. Dose adjustment is recommended. Close monitoring is required [31] |
| Oxymorphone | Bioavailability is increased in kidney dysfunction. Caution in CKD | |
| Pethidine | Risk of CNS depression or convulsions | Dose recommendation: in ESKD avoid if possible, if not, decrease dose in 50% in 8-h intervals |
| Propoxyphene | Active metabolite excretion depends on GFR. Dose adjustment is recommended. It should be avoided in ESKD | |
| Tapentadol | Low risk of withdrawal | Low risk of drug–drug interaction |
| Tramadol (centrally acting) | CNS depression | 2-fold prolonged t1/2 in reduced GFR; recommendations: decrease the dose, increase the intervals between doses, and careful monitoring |
M3G, morphine-3-glucuronide; H3G, hydromorphone-3-glucuronide; N/A, not available PK, pharmacokinetics; t1/2, half life.