Midodrine Safety Range for Orthostatic Hypotension
The FDA-approved safe dosage range for midodrine is 10 mg three times daily (total 30 mg/day), with doses given at approximately 4-hour intervals during daytime hours when upright activity is needed, and never after the evening meal or within 4 hours of bedtime to avoid supine hypertension. 1
Standard Dosing Protocol
Initial dosing should start at 10 mg three times daily, taken at approximately 4-hour intervals during daytime hours when the patient needs to be upright and active 2, 1. A suggested schedule is:
- Shortly before or upon arising in the morning
- Midday
- Late afternoon (not later than 6 PM) 1
Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently 1.
Maximum Safe Dosing
Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been systematically studied or established 1.
Single doses as high as 20 mg have been given, but severe and persistent systolic supine hypertension occurs at a high rate (approximately 45%) at this dose 1. The 10 mg dose demonstrated a 22 mmHg increase in standing systolic blood pressure with significantly better tolerability 3.
Special Population Adjustments
For patients with renal impairment, treatment should be initiated using 2.5 mg doses 1. Desglymidodrine (the active metabolite) is excreted renally, requiring cautious dosing in abnormal renal function, though this has not been systematically studied 1.
For hemodialysis patients, a single 5 mg dose administered 30 minutes before dialysis has been shown to improve intradialytic and postdialytic blood pressure 2. Midodrine is effectively cleared by hemodialysis with its half-life reduced to 1.4 hours 2.
Critical Safety Timing Restriction
Midodrine must not be given after the evening meal or less than 4 hours before bedtime to reduce the potential for supine hypertension during sleep 1. This is the most important safety consideration, as supine hypertension is a dose-limiting adverse effect.
Monitoring Requirements and Discontinuation Criteria
The supine and standing blood pressure should be monitored regularly, and midodrine should be stopped if supine blood pressure increases excessively 1.
Midodrine should be continued only in patients who demonstrate symptomatic improvement during initial treatment 2, 4, 1. The therapeutic goal is to minimize postural symptoms rather than restore normotension 5, 2, 4.
Common Adverse Effects Within Safe Range
At the standard 10 mg three times daily dosing:
- Pilomotor reactions (goosebumps) and scalp pruritus/tingling occur in approximately 13.5% of patients 2, 3
- Urinary retention or urgency occurs in 4% of patients 2, 3
- Supine hypertension occurs in approximately 8% at therapeutic doses 3
- Bradycardia and gastrointestinal symptoms may occur 5, 2
Drug Interactions Affecting Safety
Midodrine should be used cautiously with other negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) 2.
Concomitant use with other alpha-adrenergic agents should be avoided as this may aggravate supine hypertension 2.
Midodrine can antagonize alpha-adrenergic blockers (terazosin, prazosin, doxazosin) and could result in urinary retention 2.
Evidence Quality Note
The 10 mg three times daily dosing is supported by multiple randomized controlled trials demonstrating both efficacy and safety 6, 7, 3, 8, with the most recent Phase 4 post-marketing study confirming clinical benefit with good tolerability 8. The half-life of the active metabolite desglymidodrine is approximately 4 hours, supporting the three-times-daily dosing schedule 7.