Which medications are safe to use in a patient with End-Stage Renal Disease (ESRD)?

Medications Safe in End-Stage Renal Disease (ESRD)

For patients with ESRD, prioritize opioids without active metabolites (methadone, buprenorphine, fentanyl), SSRIs (particularly sertraline), acetaminophen, topical analgesics, and avoid NSAIDs, gabapentin/pregabalin, morphine, codeine, meperidine, tramadol, and tapentadol.

Pain Management

Safe Opioid Options

• Opioids without active metabolites are the preferred choice: methadone, buprenorphine, or fentanyl are most appropriate for patients with renal dysfunction 1.
• Fentanyl and buprenorphine (transdermal or intravenous) are the safest opioids in chronic kidney disease stages 4 or 5 (eGFR <30 mL/min) 1.
• Low-dose oral opioids are generally well tolerated and safe, with immediate-release formulations preferred initially for intermittent use 1.

Opioids to AVOID in ESRD

• Meperidine, codeine, and morphine must be avoided due to active metabolites that accumulate in renal insufficiency (GFR <30 mL/min/1.73 m²) 1.
• Tramadol and tapentadol are not recommended in renal insufficiency (GFR <30 mL/min/1.73 m²) and ESRD 1.
• Hydrocodone, oxycodone, and hydromorphone require caution with dose adjustment in ESRD 1.

Non-Opioid Analgesics

• Acetaminophen is widely used as initial therapy for musculoskeletal or inflammatory pain, though doses of 4 g daily may increase systolic blood pressure in hypertensive patients 1.
• Topical agents are safe alternatives: lidocaine, diclofenac, capsaicin 1.
• Less-sedating muscle relaxants (methocarbamol, metaxalone) can be used 1.

Medications to AVOID for Pain

• NSAIDs must be avoided due to cardiovascular toxicity, renal toxicity, increased bleeding risk, sodium/water retention, and increased heart failure hospitalization risk 1.
• Gabapentin and pregabalin are typically not recommended despite requiring renal dose adjustment, due to fluid retention, weight gain, and heart failure exacerbation risk 1.

Psychiatric Medications

Safe Antidepressants/Anxiolytics

• SSRIs are safe in ESRD, with sertraline being the preferred agent due to extensive study in cardiovascular disease and lower QTc prolongation risk compared to citalopram or escitalopram 1.
• Mirtazapine is safe with additional benefits including appetite stimulation and sleep promotion 1.
• Sedating antidepressants (trazodone, mirtazapine) or melatonin receptor agonists (ramelteon) can be used for insomnia after cognitive behavioral therapy 1.

Medications to AVOID for Psychiatric Conditions

• Monoamine oxidase inhibitors and tricyclic antidepressants should be avoided due to significant cardiovascular side effects including hypertension, hypotension, and arrhythmias 1.
• Hypnotics (zolpidem, eszopiclone) should be prescribed with caution due to cognitive impairment and fall risk 1.

Antimicrobial Agents

Agents Requiring Dose Adjustment

• Ciprofloxacin requires dose reduction: 250-500 mg q12h for creatinine clearance >50 mL/min; 250-500 mg q18h for 10-50 mL/min; 250-500 mg q24h for <10 mL/min 1.
• Levofloxacin: 500 mg loading dose, then 250 mg q24h for creatinine clearance 50-80 mL/min; 250 mg q48h for <50 mL/min 1.
• Trimethoprim-sulfamethoxazole: reduce to half dose for creatinine clearance 15-30 mL/min; half dose or use alternative for <15 mL/min 1.
• Fluconazole requires 50% dose reduction for creatinine clearance <50 mL/min 1.

Hepatitis C Treatment

• Glecaprevir/pibrentasvir is the treatment of choice for chronic hepatitis C with stage 4 or 5 CKD, including hemodialysis patients, with 99% SVR rates 1.
• Sofosbuvir-based regimens can be used when no other relevant treatment options are available, though sofosbuvir metabolite exposure increases 20-fold in ESRD 1.
• Sofosbuvir/ledipasvir has no dose recommendation for severe renal impairment (eGFR <30 mL/min/1.73 m²) or ESRD, but can be used when alternatives unavailable 1.

Other Medications

Safe Options

• Theophylline requires no dosage adjustment in adults and children >3 months with ESRD, as only 10% is excreted unchanged and active metabolites don't accumulate 2.
• Loop diuretics are the agents of choice in ESRD, though higher doses are needed due to pharmacokinetic changes 3.
• Insulin is the preferred treatment for diabetes requiring medication in ESRD 4.

Immunosuppressive Agents in Rheumatic Disease

• Hydroxychloroquine requires more frequent monitoring for adverse reactions 5.
• Mycophenolate mofetil, cyclosporine A, and tacrolimus require therapeutic drug monitoring 5.
• Cyclophosphamide and azathioprine need dose adjustments 5.
• Methotrexate and bucillamine are contraindicated in ESRD 5.
• Leflunomide and sulfasalazine do not require significant dose reduction 5.
• Biological agents (rituximab, belimumab) are not affected by ESRD and require no dose adjustments 5.

Critical Pitfalls

• Always check for active metabolites when prescribing opioids—accumulation causes respiratory depression, falls, and confusion 1.
• Avoid combining sedating medications with antihypertensives and diuretics due to amplified fall risk and orthostatic hypotension 1.
• Monitor closely when initiating or stopping medications as ESRD patients have altered pharmacokinetics requiring frequent dose adjustments 6, 4.
• Preserve peripheral veins in stage III-V CKD patients for future hemodialysis access 4.