What sleeping medication is recommended for patients with End-Stage Renal Disease (ESRD)?

Sleeping Medication for ESRD Patients

Primary Recommendation

For ESRD patients requiring sleep medication, ramelteon (8 mg at bedtime) is the safest first-line option because it undergoes hepatic metabolism, requires no dose adjustment in renal failure, and has minimal adverse effects. 1

Medication Selection Algorithm

First-Line: Ramelteon

• Ramelteon 8 mg taken at bedtime is the preferred agent because it is a melatonin receptor agonist that does not rely on renal excretion and carries no risk of accumulation in ESRD 2, 1
• The most common adverse effects are somnolence (3%), fatigue (3%), dizziness (4%), and nausea (3%), which are generally mild 1
• No dose adjustment is required for renal impairment 1
• This medication is particularly appropriate for sleep-onset insomnia 2

Second-Line: Short-Acting Benzodiazepine Receptor Agonists (BzRAs)

If ramelteon is ineffective, consider hepatically-metabolized BzRAs:

• Zaleplon 10 mg at bedtime is the safest BzRA option for ESRD patients because it has the shortest half-life and is metabolized hepatically 2

• Reduce to 5 mg in elderly or debilitated patients 2

• Primarily useful for sleep-onset insomnia, can be used for maintenance insomnia if at least 4 hours of sleep time remains 2

• Zolpidem 10 mg at bedtime (immediate-release) is another hepatically-metabolized option 2

• Reduce to 5 mg in elderly or debilitated patients 2

• Short to intermediate-acting, primarily for sleep-onset insomnia 2

Medications to AVOID in ESRD

Critical warning: Multiple sleeping medications are associated with increased risk of CKD progression to ESRD and should be avoided or used with extreme caution:

• Benzodiazepines (clonazepam, diazepam, estazolam, flunitrazepam, nitrazepam) are associated with increased CKD risk and progression to ESRD 3
• Zolpidem and zopiclone are also associated with increased CKD risk despite being non-benzodiazepine hypnotics 3
• Trazodone is associated with increased CKD risk 3
• Flurazepam should be avoided due to its extended half-life and risk of accumulation 2

Special Considerations for ESRD

• All sedative-hypnotics should be used with extreme caution because ESRD patients have highly complex medication regimens and are at disproportionately high risk for medication-related problems and adverse drug events 4, 5
• Medication reconciliation is critically important in dialysis patients to avoid drug-related problems 4, 5
• The dialysis facility should serve as the coordination center for medication management 4

When Sedating Antidepressants Are Considered

If comorbid depression exists or other treatments fail:

• Low-dose sedating antidepressants may be considered, though evidence for efficacy is weak 2
• These are NOT FDA-approved for insomnia 2
• However, trazodone specifically is associated with increased CKD risk and should be avoided in ESRD patients 3

Critical Pitfalls to Avoid

• Never use benzodiazepines as first-line therapy in ESRD patients given the association with CKD progression to ESRD 3
• Avoid medications with renal excretion that can accumulate in ESRD 2
• Do not prescribe sleeping pills on an empty stomach - administration should be timed appropriately 2
• Caution patients about complex sleep-related behaviors (sleepwalking, sleep-driving, sleep-eating) associated with BzRAs 2
• Avoid combining sleeping medications with alcohol or other CNS depressants 2
• Monitor for signs of depression as caution is advised when depression is present 2

Non-Pharmacological Approaches

• Address underlying causes first: evaluate for medications that may worsen sleep, optimize dialysis adequacy, and assess for sleep-disordered breathing 6, 7
• Behavioral interventions should be implemented alongside any pharmacotherapy 7