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)