Table 1 |.
Pharmacological considerations for opioid use in patients with HDKF
| Medication (MW in g/mol) | Typical pharmacokinetic properties | Pharmacokinetics in patients with HDKF | Effects of dialysis | Use and dosing information in hDKF | ||
|---|---|---|---|---|---|---|
| PB (%) | VD (L/kg) | t1/2 (hr) | ||||
| Codeine (299.4) | 7–25 | 3–6 | 3 | t1/2 of metabolites substantially greater in patients with HDKF than in healthy controls166,167 | Metabolites substantially removed by HD166 | Not recommended Risk of death increased in patients with CYP2D6 polymorphism Drug accumulation might result in serious adverse drug events, including severe hypotension, narcolepsy and respiratory depression |
| Fentanyl (336.5) | 85 | 4 | 7 | Inverse relationship between degree of azotaemia and fentanyl clearance168,169 | No significant removal by HD170, including high-efficiency or high-flux HD membranes169 | May be used but consider a 25% dose reduction53 No supplemental dose needed with HD |
| Hydrocodone (299.4) | 36 | 5 | IR: 4 ER: 9 |
t1/2 increased in patients with HDKF compared with healthy controls171 | Minimal clearance by HD171 | Initiate treatment at a low dose (generally 50% reduction)53 Carefully monitor patients during titration to an effective dose |
| Hydromorphone (285.3) | 8–19 | 4 | IR: 2–3 ER: 8–15 |
Primary metabolite H3G accumulates in patients with kidney failure172,173 | Parent drug and primary metabolite H3G efficiently removed by HD172,174 | May be used but consider a 75% dose reduction53 No supplemental dose needed with HD |
| Meperidine (247.3) | 60–80 | 3–4 | 3–5 | Meperidine and its active metabolite normeperidine accumulate in patients with kidney failure175 | HD efficiently removes meperidine and its metabolite normeperidine175,176 | Not recommended Meperidine and normeperidine increase the risk of seizures and are highly neurotoxic HD has been used to treat normeperidine neurotoxicity176 |
| Methadone (309.4) | 85–90 | 1–8 | 7–59 | t1/2 of methadone is variable and may be increased in patients with HDKF172 177–179 | Methadone and primary metabolite EDDp not significantly removed by HD or PD172 177 178 | May be used but consider a 25–50% dose reduction53,180 No supplemental dose needed with HD |
| Morphine (285.3) | 35 | 5.3 | 2–3 | Morphine and its active metabolites M6G and M3G accumulate substantially in patients with HDKF181 | Minimal clearance of morphine by PD181 Average 37% extraction of morphine during HD session170 |
Not recommended Accumulation of M3G and M6G is associated with serious adverse events including myoclonus, seizures, sedation and respiratory depression Serious adverse drug events related to use of morphine in patients with kidney failure are well documented104,182,183 Use with extreme caution; reduce dose by 75%53,180 |
| Oxycodone (315.4) | 45 | 2.6 | IR: 3.2 ER: 4.5 |
t1/2 of oxycodone increased in patients with HDKF184–186 | Oxycodone removed by HDF (54%) and HD (22%); primary metabolite noroxycodone removed by HDF (27%) and HD (17%)185 | May be used but consider a 75% dose reduction53 No supplemental dose needed with HD Uncertainty regarding variable individual response and prolonged effects with long-acting formulations Drug concentration might be significantly altered in patients with CYP2D6 polymorphism and patients might be at increased risk of drug interactions with CYP2D6 inducers or inhibitors104,183,187 |
| Tramadol (263.4) | 20 | 2.9 | 6 | t1/2 of tramadol may be increased in patients with HDKF188 | Substantial removal by HD | Dose every 12 h53 Reduce dose by 50%188 |
CYP, cytochrome P450; EDDP, 2- ethylidene-1,5- dimethyl1–3,3- diphenylpyrrolidine; ER, extended release; H3G, hydromorphone-3- glucuronide; HD, haemodialysis; HDF, haemodiafiltration; HDKF, HD- dependent kidney failure; IR, immediate release; M3G, morphine-3- glucuronide; M6G, morphine-6- glucuronide; MW, molecular weight; PB, protein binding; PD, peritoneal dialysis; t1/2, drug half-life; VD, volume of distribution.