Montelukast (Singulair) in End-Stage Renal Disease
Montelukast is safe for ESRD patients on dialysis and requires no dose adjustment. 1
Pharmacokinetic Rationale
Montelukast has favorable pharmacokinetic properties that make it safe in ESRD:
- Biliary excretion is the primary elimination route, with montelukast and its metabolites excreted almost exclusively via bile (86% fecal recovery, <0.2% urinary recovery) 1
- Renal insufficiency does not alter pharmacokinetics because the drug is not renally eliminated, eliminating the need for dose adjustment 1
- High protein binding (>99.9%) prevents significant removal by dialysis, similar to other highly protein-bound medications 2
Dosing Recommendations
- Standard dose of 10 mg once daily should be used without modification in ESRD patients 1, 3, 4
- No therapeutic drug monitoring required, unlike medications such as aminoglycosides that necessitate serum concentration monitoring in ESRD 2
- No timing considerations with dialysis sessions are necessary, as the drug is not dialyzable 2, 1
Clinical Evidence in ESRD Populations
Multiple studies have demonstrated both safety and efficacy of montelukast in hemodialysis patients:
- A randomized controlled trial in 16 hemodialysis patients with refractory uremic pruritus showed 35% reduction in pruritus with montelukast versus 7% with placebo (P = 0.002), with satisfactory compliance and safety 3
- A larger double-blind trial of 80 hemodialysis patients demonstrated significant reduction in visual analogue scale scores (2.73 ± 2.03 vs 5.47 ± 2.37 in placebo, P < 0.001) and Detailed Pruritus Scores (3.24 ± 2.2 vs 6.44 ± 3.25, P < 0.001) 4
- High-sensitivity C-reactive protein decreased in the montelukast group (5.48 to 3.86 µg/mL) while increasing in placebo (6.69 to 8.14 µg/mL), suggesting anti-inflammatory benefits 4
Safety Profile
- No hepatic dose adjustment needed in mild-to-moderate hepatic insufficiency, though montelukast has not been evaluated in severe hepatic impairment 1
- Medication reconciliation should be performed at every care transition for ESRD patients taking montelukast, particularly when moving between hospital, dialysis unit, and rehabilitation settings 2
- While neuropsychiatric events (anxiety, depression, sleep disturbance, suicidality) have been reported with montelukast in general populations, data remain insufficient to establish causality 5
Practical Clinical Application
Prescribe montelukast 10 mg once daily without regard to dialysis timing or dose modification. Unlike many medications requiring interval adjustment or dose reduction in ESRD (such as antimicrobials, antiretrovirals, or sofosbuvir), montelukast maintains its standard dosing regimen 6, 2, 1. This simplifies medication management in a population already burdened by polypharmacy and complex dosing schedules 2.