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Pharmacokinetic data on analgesic medications in the normal state and in the context of advanced chronic kidney disease

Pharmacokinetic data on analgesic medications in the normal state and in the context of advanced chronic kidney disease
Medication Percent excreted in the urine T one-half normal (hours) T one-half dialysis (ESKD) (hours) Hemodialysis Peritoneal dialysis Comments and recommendations on use in advanced CKD*
Acetaminophen (paracetamol)[1-4] <5 1 to 4 Unchanged Dialyzed Not dialyzed Accumulation of inactive metabolites. Analgesic of choice for mild-moderate pain. No dose reduction required.
Codeine[5-7] 0 to 16 2.5 to 4 13 to 18.9 Not dialyzed Unlikely to be dialyzed Metabolized to morphine derivatives and known to cause profound hypotension and CNS and respiratory depression. Not recommended in advanced CKD.
Tramadol[8-10] 90 (30 unchanged; 60 as metabolites) 6 11 Dialyzed Unknown Unpredictable risk of serious overdosing or underdosing after administration of standard doses. Not recommended in advanced CKD.
Morphine 10 2 to 3 Unchanged Parent and active metabolites dialyzed Not dialyzed Rapid accumulation of active metabolites in advanced CKD resulting in clinically significant opioid toxicity including sedation, confusion, myoclonus, and respiratory depression. Not recommended in advanced CKD.
Hydromorphone[11,12] 6 2 to 5 3.2 on dialysis; 5.9 nondialysis days Active metabolite (H3G) dialyzed Unknown Much better tolerated in advanced CKD than morphine with less toxic metabolites. Pharmacodynamic data have shown less neuroexcitation compared with morphine and a greater than 65% reduction in pain over dosing intervals with no clinically significant opioid toxicity when given in low doses and monitored carefully.
Fentanyl[13] <7 2 to 7 Possibly increased Not dialyzed Not dialyzed Inactive metabolites. Most pharmacokinetic studies in advanced CKD use parenteral rather than transdermal fentanyl. Generally considered safe for use in advanced CKD if monitored carefully.
Alfentanil[14] 0.4 1 to 2 Unchanged Not dialyzed Not dialyzed Although pharmacokinetics of fentanyl analogs alfentanil and sufentanil do not appear to differ in advanced CKD, there is a single case report of prolonged respiratory depression in a patient with ESKD where there was an elevated plasma concentration of sufentanil.
Buprenorphine[15-18] Minimal 30 Unchanged Dialyzed Dialyzed Buprenorphine may be given in standard doses to patients with advanced CKD. Generally considered safe for use in advanced CKD if monitored carefully.
Oxycodone[19-22] <10 2 to 4 3 to 5 Dialyzed Unknown There are case reports of toxicity in association with advanced CKD, yet overall consensus from the literature is that oxycodone is reasonably safe to use in advanced CKD if monitored carefully.
Methadone[23,24] 15 to 60 13 to 47 Unknown Not dialyzed Not dialyzed Primarily excreted in the feces. Plasma concentrations are similar in advanced CKD compared with those with normal kidney function. Generally considered safe for use in advanced CKD if monitored carefully.
Gabapentin[25-27] Approximately 100 5 to 7 52 to 132 Dialyzed Possibly dialyzed Freely crosses the blood-brain barrier. Dose postdialysis. The following are maximum doses:  
  • eGFR 50 to 79 mL/min/1.73 m2: 600 mg three times per day
  • eGFR 30 to 49 mL/min/1.73 m2: 300 mg three times per day
  • eGFR 15 to 29 mL/min/1.73 m2: 300 mg twice per day
  • eGFR <15 mL/min/1.73 m2: 300 mg once per day
Pregabalin[28,29] 92 to 99 5 to 6.5 Increased Dialyzed (50% dialyzed in four hours) Dialyzed

Similar mechanism of action as gabapentin. Can give supplementary dose postdialysis (75 mg).

Dose regimen equivalent to approximately 600 mg per day of pregabalin in patient with normal kidney function:
  • eGFR >30 to 60 mL/min/1.73 m2: 150 mg twice per day
  • eGFR 15 to 30 mL/min/1.73 m2: 150 mg once per day
  • eGFR <15 mL/min/1.73 m2: 75 mg once per day
Carbamazepine[30] 3 to 5 35 Unchanged Dialyzed Unknown Start at 100 mg daily or twice daily and increase by 100 mg daily to a maximum of 1200 mg daily.
Duloxetine[6,31] <1 8 to 17 Unchanged Not dialyzed Not dialyzed Reduced starting dose in advanced CKD (30 mg) with a maximum dose of 60 mg per day. Some sources recommend avoiding in patients with a CrCl of <30 mL/min. Others suggest starting at a very low dose and increase according to response, with a maximum dose of 30 mg daily.
Ketamine[6] 2 to 4 2 to 4 Unchanged Not dialyzed Unlikely to be dialyzed Dose as per normal kidney function.
Amitriptyline[32,33] <2 9 to 25 Unchanged Not dialyzed Not dialyzed Although no dose reduction is required, a low starting dose is recommended given likelihood of anticholinergic adverse effects.
Detailed dosing and dose adjustment recommendations for use in patients with advanced CKD are available in the individual drug monographs (Lexicomp) included within UpToDate.
ESKD: end-stage kidney disease; CKD: chronic kidney disease; CNS: central nervous system; H3G: hydromorphone-3-glucuronide; eGFR: estimated glomerular filtration rate; CrCl: creatinine clearance.
*Advanced CKD: CKD with eGFR <30 mL/min/1.73 m2
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From: Davison SN, Koncicki H, Brennan F. Pain in chronic kidney disease: A scoping review. Semin Dial 2014; 27:188. http://onlinelibrary.wiley.com/doi/10.1111/sdi.12196/abstract. Copyright © 2014 Wiley Periodicals, Inc. Modified and reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: permissions@wiley.com or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (http://onlinelibrary.wiley.com).
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