Chronic Kidney Disease
Table 1: Preferred Analgesics in Chronic Kidney Disease Stage 4 and 5 WHO Analgesic
Preferred
Ladder Category Analgesic Step 1
Acetaminophen CKD 4 and 5
Without Dialysis Recommended
Intermittent Hemodialysis Recommended
Additional Comments
3.2 g maximum daily dose in the elderly or those on dialysis
Step 2
NSAID use discouraged in CKD, particularly in patients with residual urine output, advanced age or multiple comorbidities. NSAID-based topical gels are acceptable on small joints, applied up to three times daily. Maximum daily dose 200 mg in CKD 4 and 100 mg in CKD 5. Dose every 12 hours. Use cautiously.
Tramadol Oxycodone
Starting dose 2.5 mg by mouth every 8–12 hours.
Step 3 Hydromorphone
Maximum daily dose 200 mg. Dose every 12 hours.
Use cautiously. Dialysis removal unclear.
Mild analgesics unsafe in CKD: codeine, merperidine, and propoxyphene Use cautiously, especially if stage 5 CKD and not on
dialysis. Starting dose 0.5 mg every 6 hours. Switch to transdermal fentanyl if daily dose exceeds 9 mg.
Fentanyl
Transdermal dose dependent on baseline opioid dose. Subcutaneous dose 25 μg every 4 hours as needed.
Methadone
Reduce dose and increase dosing intervals.
Starting dose 0.5 mg every 6 hours. Switch to transdermal fentanyl if daily dose exceeds 9mg.
H3G is removed on dialysis
Transdermal dose dependent on baseline opioid dose Subcutaneous dose 25 μg
every 4 hours as needed. Dialysis removal of drug and metabolites limited. Reduce dose and increase dosing intervals.
Buprenorphine Use cautiously.
Reduce dose and increase dosing intervals.
Dialysis removal of drug and metabolites limited. Use cautiously.
Reduce dose and increase dosing intervals.
Metabolites inactive.
Do not use transdermal patch in opioid-naïve patients.
Renal clearance of tramadol and metabolites
Parent drug and metabolites may accumulate causing CNS depression.
H3G accumulation may cause neuro-excitatory or analgesic antagonism.
Pharmacokinetic variability large.
Metabolites inactive and cleared via the bowel. Special prescriber licensing may be required.
Anticipate limited removal with dialysis.
Strong analgesics unsafe in CKD: morphine. Accumulation of parent drug and metabolites including M6G causes toxicity that includes CNS sedation. Can be dialyzed but effects may be prolonged due to M6G accumulation in CNS tissue.
CKD = chronic kidney disease, CNS = central nervous system, H3G = hydromorphone-3-glucuronide, M6G = morphine-6-glucuronide, NSAID = non-steroidal anti-inflammatory drug, WHO = World Health Organization.
excreted in the urine.56 may be compounded by antidepressants, seizure history or CKD.57
Reported complications include seizures. Risk While
use has been limited by a ceiling effect, efficacy was demonstrated in moderate to severe cancer pain, including those with neuropathic pain.57,58
In advanced CKD, the elimination half-life may double.59 A
maximum daily dose of 200 mg taken 12-hourly is suggested for dialysis patients and those with a creatinine clearance of 15–30 ml/minute. Negligible amounts are removed with dialysis.60
For patients with
creatinine clearance below 15 ml/minute and not receiving dialysis, a maximum total daily dose of 100 mg is recommended.61
Extended-
release preparations are discouraged. Toxicity is incompletely reversed by naloxone.
Propoxyphene and Merperidine
Propoxyphene (which is no longer available in North America) and merperidine are contraindicated in CKD patients due to accumulation and subsequent life-threatening cardiac complications, central nervous system (CNS) sedation, delirium, and seizures.62
24 Step 3
For patients with severe pain or on-going moderate pain despite weak opioids, strong opioids are recommended. Those believed most efficacious and safe in CKD patients are hydromorphone, methadone, and fentanyl.
Hydromorphone
Hydromorphone is a semi-synthetic opioid agonist with excellent efficacy in moderate to severe pain. It has five to seven times the potency of
US NEPHROLOGY Morphine
Morphine is not recommended for chronic pain management. A cornerstone for moderate to severe pain in the general population, morphine is metabolized in the liver to the potent morphine-6-glucuronide (5–10 %) and less-active morphine-3-glucuronide (45–55 %). Metabolites are renally excreted in direct relationship to creatinine clearance.63
Morphine can be
dialyzed but prolonged toxicity from morphine-6-glucuronide accumulation has been observed. In ESRD, particularly among those not receiving dialysis, accumulation and toxicity are anticipated with chronic use.13,14,64
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