Is lemborexant safe and appropriately dosed for a patient with end‑stage renal disease (chronic kidney disease stage 5) on hemodialysis and hyperthyroidism who has persistent insomnia?

Lemborexant Use in CKD Stage 5 on Hemodialysis with Hyperthyroidism and Persistent Insomnia

Lemborexant is safe and does not require dose adjustment in patients with end-stage renal disease on hemodialysis, making it an appropriate choice for this patient's persistent insomnia.

Pharmacokinetic Profile in Severe Renal Impairment

• Lemborexant exposure (AUC) increases approximately 1.5-fold in patients with severe renal impairment (eGFR 15-29 mL/min) compared to those with normal renal function, while peak concentrations (Cmax) remain similar 1
• Despite this modest increase in exposure, the pharmacokinetic alterations are not sufficiently significant to warrant dose adjustment in patients with renal impairment 1
• The drug is highly protein-bound (>99.9%), making it unlikely to be removed by hemodialysis 2
• Lemborexant is primarily eliminated through hepatic metabolism rather than renal excretion, with unchanged drug accounting for only 13.0% of fecal elimination and being undetectable in urine 3

Dosing Recommendations

Standard dosing of lemborexant 5 mg or 10 mg once daily at bedtime should be used without modification in hemodialysis patients 1

• No therapeutic drug monitoring is required for lemborexant in ESRD patients, unlike medications such as cycloserine or aminoglycosides 2
• The timing of administration relative to dialysis sessions is not critical due to the drug's high protein binding and minimal dialytic clearance 2
• The mean effective half-life of 17-19 hours for the 5-10 mg doses supports once-daily dosing 4

Safety Profile in Renal Impairment

• All treatment-emergent adverse events in the severe renal impairment study were mild or moderate in severity 1
• The most common adverse effects are somnolence (7.65%) and headache, with no marked cognitive or psychomotor impairment observed 5, 6
• No serious adverse drug reactions related to suicidal ideation or behavior were observed in postmarketing surveillance 6
• Lemborexant demonstrates a favorable safety profile compared to benzodiazepines and Z-drugs, particularly important in patients with multiple comorbidities 5

Special Considerations for This Patient

Hyperthyroidism Impact

• Hyperthyroidism itself can contribute to insomnia and should be optimally managed concurrently with lemborexant therapy
• No specific drug interactions between lemborexant and antithyroid medications have been reported

Medication Administration Principles in Hemodialysis

• While general principles recommend administering medications after hemodialysis to prevent premature drug removal 7, 8, this is not necessary for lemborexant due to its high protein binding and minimal dialytic clearance 2
• ESRD patients are at heightened risk for adverse drug reactions due to polypharmacy and altered pharmacokinetics, making medication reconciliation critical at every care transition 2

Clinical Efficacy

• Lemborexant significantly reduces subjective sleep onset latency and increases total sleep time, with efficacy rates of approximately 81% in real-world clinical practice 6
• Improvements in sleep parameters are observed starting from Week 8 of treatment and are sustained with continued use 6
• No next-morning residual sleepiness or impairment in psychomotor performance occurs at therapeutic doses through 10 mg 4

Common Pitfalls to Avoid

• Do not reduce the lemborexant dose based solely on renal function, as the modest increase in exposure does not translate to clinically significant safety concerns 1
• Do not assume dialytic clearance requires post-dialysis supplementation, as the drug's high protein binding prevents significant removal 2
• Do not overlook hyperthyroidism management, as inadequately controlled thyroid disease will perpetuate insomnia regardless of hypnotic therapy