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. Author manuscript; available in PMC: 2021 Nov 1.
Published in final edited form as: Curr Opin Nephrol Hypertens. 2020 Nov;29(6):671–680. doi: 10.1097/MNH.0000000000000646

Table 1.

Recommended non-opioid medications in patients with kidney disease

Medication Metabolism and PK comments Dosing in CKD Dosing in ESKD Comments
Medications for nociceptive pain
Acetaminophen Hepatic, excreted in the urine primarily as non-toxic metabolites
High oral bioavailability 85-98%
Median onset 11 minutes and median duration of action ~ 4 hours after 1000 mg oral dose [83]
ClCr 10-50 mL/min: 650 mg q 6h prn
Max daily dose 4000 mg
ClCr < 10 mL/min or dialysis: 650 mg q 8h prn
Max daily dose 4000 mg [84]
Use scheduled doses instead of as needed for continuous pain control
Use with caution and Lower max daily dose (2000 mg) if liver disease or daily alcohol
NSAIDs, preferably COX-2 selective agents such as celecoxib Reduce dose and increase dosing interval, use for short term (</= 5 days only)
Contraindicated in CKD stage 5
No dose adjustment, use for short term only Monitor for volume retention, cardiotoxicity, renal and gastrointestinal toxicity
Topical analgesics (NSAIDs, lidocaine, capsaicin) Systemic exposure with topical NSAIDs is 2-3% than with oral, but increases with higher dose applied to larger surface area [85] Avoid high dose topical NSAID use over large surface area
Medications for neuropathic pain
Pregabalin Negligible, 90% excreted renally as unchanged drug
High oral bioavailability ≥ 90%
Onset of pain relief ~ 1 week
Max daily dose:
ClCr 30-60 mL/min: 300 mg daily (2-3 divided doses)
ClCr 15 to 30 mL/min: 150 mg daily (1-2 divided doses)
ClCr < 15 mL/min: 75 mg daily (single dose)
Start at 25 mg once daily, Maximum dose 75 mg once daily
Well dialyzed, Dose post-HD
Start at low dose and uptitrate every 1-2 weeks, monitor for altered mental status and falls
Gabapentin Not metabolized, excreted renally as unchanged drug
Bioavailability is dose dependent: is upto 80% with 300mg/d but decreases as dose increases to <50% above 1200 mg/d
Max daily dose:
ClCr 50-79 mL/min: 1800 mg daily (3 divided doses)
ClCr 30-49 mL/min: 900 mg/day (2-3 divided doses)
ClCr 15-29 mL/min: 600 mg/day (1-2 divided doses)
ClCr < 15 mL/min: 300 mg/day (single dose)
Maximum dose 300 mg once daily
Well dialyzed, Dose post-HD
Start at low dose and uptitrate every 1-2 weeks, monitor for altered mental status and falls
Duloxetine Extensively metabolized in the liver via CYP1A2 and 2D6 to inactive metabolites, Oral bioavailability 30-80%, >90% protein bound
Excretion: renal 70%, fecal 20%
Start with 20 mg daily
Max daily dose: 60 mg
ClCr 30-80 mL/min: no dose adjustment necessary
ClCr < 30 mL/min: avoid use
Avoid use (limited data) Monitor for hyponatremia, can rarely cause serotonin syndrome
Venlafaxine Hepatically metabolized via CYP2D6 to active metabolite, O-desmethylvenlafaxine. Bioavailability is ~ 13% for immediate release and 45% for extended release, primarily excreted renally Extended release: Start at 37.5 mg once daily
Max daily dose:
ClCr 30-89 mL/min: 150 mg daily
ClCr <30 mL/minute: 112.5 mg daily
Extended release: Start at 37.5 mg once daily
Max daily dose: 112.5 mg daily
Poorly dialyzed
Monitor for hyponatremia, can rarely cause serotonin syndrome
Desvenlafaxine (active metabolite of venlafaxine) Hepatically metabolized
Oral bioavailability approximately 80%.
Excreted renally approximately 45% as unchanged drug and 24% as metabolites
Max daily dose:
ClCr 30-50 mL/min: 50 mg once daily
ClCr <30 mL/min: 25 mg once daily or 50 mg every other day
Max daily dose: 25 mg once daily or 50 mg every other day.
Poorly dialyzed
Monitor for hyponatremia, can rarely cause serotonin syndrome
Amitriptyline Hepatically metabolized to nortriptyline (active metabolite)
Oral doses are completely and rapidly absorbed, > 90% protein bound.
Excreted renally as metabolites, 18% as unchanged drug.
Start at 10 mg once daily at bedtime, No dose adjustment recommended
Maximum dose 150 mg daily.
Start at 10 mg once daily at bedtime, No dose adjustment recommended
Maximum dose 150 mg daily.
Poorly dialyzed
Limited evidence in CKD
The Beers Criteria recommends avoidance in older adults (strong anticholinergic properties, sedation, orthostatic hypotension, urinary retention)