Bedtime Doxazosin Administration in Dialysis Patients
Yes, doxazosin can be safely administered at bedtime to dialysis patients, and this timing is actually preferable for optimal blood pressure control throughout the 24-hour period, particularly for morning hypertension. 1, 2
Pharmacokinetic Safety in Renal Impairment
Doxazosin does not require dose adjustment in dialysis patients because pharmacokinetic studies demonstrate no significant alterations in patients with renal impairment compared to those with normal renal function. 1
The drug undergoes extensive hepatic metabolism (primarily via CYP3A4) with only 4.8% excreted unchanged in feces and trace amounts in urine, making renal clearance negligible. 1
The terminal elimination half-life remains approximately 22 hours regardless of renal function status. 1
Optimal Timing: Bedtime Administration
Bedtime dosing of doxazosin provides superior 24-hour blood pressure control compared to morning administration, which is particularly important for dialysis patients who often struggle with morning hypertension. 2
Evidence for Bedtime Dosing:
Morning administration fails to provide adequate 24-hour coverage, showing only minimal and non-significant BP reductions (1.8/3.2 mmHg in monotherapy) with essentially no effect on nocturnal blood pressure. 2
Bedtime administration produces significantly greater BP reduction (6.9/5.9 mmHg systolic/diastolic in monotherapy; 5.3/4.5 mmHg in combination therapy) that is sustained throughout both day and nighttime hours. 2
Bedtime doxazosin effectively controls morning hypertension, which is measured by home blood pressure monitoring and is particularly problematic in patients with chronic kidney disease. 3, 4
Blood Pressure Management in Dialysis
The K/DOQI guidelines emphasize that hypertension management in dialysis patients requires attention to both fluid status and antihypertensive medications. 5
Antihypertensive drugs should be given preferentially at night to reduce nocturnal blood pressure surge and minimize intradialytic hypotension that may occur with morning dosing before dialysis sessions. 5
Target predialysis blood pressure should be <140/90 mmHg and postdialysis <130/80 mmHg. 5
Drugs that inhibit the renin-angiotensin system (ACE inhibitors or ARBs) are preferred for dialysis patients, but doxazosin can be used as adjunctive therapy. 5
Renal Protective Effects
Doxazosin demonstrates renal protective actions in patients with chronic renal failure, making it particularly suitable for dialysis patients:
Treatment with doxazosin (average dose 5.6 mg/day) was associated with increased glomerular filtration and decreased plasma BUN and creatinine levels in chronic renal failure patients. 6
Proteinuria decreased significantly from 1.8 mg/day to 1.3 mg/day with doxazosin treatment. 6
The reduction in mean blood pressure correlated significantly with decreased proteinuria (r=0.048, p=0.007). 6
Important Caveats and Monitoring
Heart Failure Risk:
Doxazosin can increase left ventricular diameter and carries a risk of congestive heart failure, particularly in patients not taking diuretics. 7
Prior use of diuretics can prevent unfavorable effects on left ventricular structure, so ensure dialysis patients are adequately volume-managed through ultrafiltration. 7
Three cases of congestive heart failure occurred in the doxazosin group versus none in controls in one study, though this was in the context of inadequate volume management. 7
Dosing Considerations:
Start with 2 mg at bedtime and titrate as needed for blood pressure control. 1, 6
Higher doses (up to 8 mg/day) can be safely given to patients with chronic renal failure without dose adjustment. 6
Peak plasma levels occur 2-3 hours after dosing, which with bedtime administration provides optimal morning blood pressure control. 1
Dialyzability:
Consider whether doxazosin is removed during dialysis when timing the dose, though given its high protein binding (98%) and hepatic metabolism, dialytic removal is likely minimal. 5, 1
The guideline recommendation to give antihypertensives at night rather than morning before dialysis helps avoid intradialytic hypotension. 5