Is Isosorbide Dialyzable?
Isosorbide dinitrate is partially removed by hemodialysis, while isosorbide mononitrate shows minimal to no significant dialytic clearance.
Hemodialysis Effects on Isosorbide Dinitrate
Hemodialysis significantly removes isosorbide dinitrate from the blood, with studies showing approximately 20% reduction in peak concentration (Cmax), 30% reduction in area under the curve (AUC), and an increase in plasma clearance by 81 ml/min during dialysis sessions 1.
The half-life of isosorbide dinitrate decreases from approximately 4.3 hours to 3.4 hours during hemodialysis, confirming active removal of the drug 1.
Despite this dialytic clearance, the FDA label states that it is not known which substances can usefully be removed by hemodialysis and provides no specific guidance on supplemental dosing post-dialysis 2.
Peritoneal Dialysis Considerations
- Continuous ambulatory peritoneal dialysis (CAPD) does not result in important loss of isosorbide-5-nitrate, making dose adjustments unnecessary for patients on this modality 1.
Isosorbide Mononitrate in Renal Failure
Isosorbide mononitrate shows minimal accumulation in patients with renal failure, with only somewhat higher plasma concentrations of the 5-mononitrate metabolite observed in uremic patients compared to those with normal renal function 3.
The pharmacokinetic profile remains largely unchanged between patients with and without renal failure after oral administration 3.
Clinical Implications for Dosing
No formal dose adjustment is recommended for isosorbide dinitrate or isosorbide mononitrate in patients with renal impairment or those on dialysis, based on current guidelines 4.
The combination of hydralazine and isosorbide dinitrate can be useful in patients with heart failure who have renal insufficiency and cannot tolerate ACE inhibitors or ARBs 4.
Important Caveats
While isosorbide dinitrate is partially dialyzable, the clinical significance of this removal is unclear, and no controlled studies have established whether timing doses around dialysis sessions improves outcomes 2.
The high protein binding of many cardiovascular drugs typically limits dialytic clearance, but isosorbide dinitrate represents an exception with measurable removal 1.
Patients with renal disease receiving isosorbide therapy require careful monitoring for hypotension and volume status, as treatment resulting in central volume expansion carries risks in this population 2.