What is the starting dose of midodrine (ProAmatine) for orthostatic hypotension?

Starting Dose of Midodrine for Orthostatic Hypotension

The FDA-approved starting dose of midodrine is 10 mg three times daily, taken at approximately 4-hour intervals during daytime hours when the patient needs to be upright. 1

Standard Dosing Protocol

• Begin with 10 mg three times daily as the initial dose, administered during waking hours when upright activity is required 2, 1
• The recommended dosing schedule is approximately 4-hour intervals: shortly before or upon arising in the morning, at midday, and in 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

Alternative Lower Starting Dose for Special Populations

• For patients with renal impairment, initiate treatment at 2.5 mg three times daily, as desglymidodrine (the active metabolite) is excreted renally 1
• For hemodialysis patients specifically, a single 5 mg dose administered 30 minutes before dialysis has been shown effective for intradialytic and postdialytic blood pressure improvement 2

Critical Timing Considerations to Prevent Supine Hypertension

• The last dose must be taken at least 4 hours before bedtime to reduce the risk of supine hypertension during sleep 1
• Midodrine should not be given after the evening meal 1
• The first dose should be taken before arising in the morning, ideally while still in bed 3

Evidence Supporting the 10 mg Starting Dose

• Multiple randomized controlled trials demonstrated that 10 mg doses significantly increased standing systolic blood pressure by approximately 22-27 mmHg (28%) compared to placebo (p < 0.001) 4, 5
• The 10 mg dose improved symptoms of dizziness, lightheadedness, syncope, weakness, and energy level compared to placebo (p < 0.05 or better) 4, 6, 5
• A dose-response study confirmed a significant linear relationship between midodrine dosage and mean systolic blood pressure increase, with peak effect at 1 hour post-dose 7
• The half-life of desglymidodrine is approximately 4 hours, supporting the three-times-daily dosing schedule 7

Dose Titration Parameters

• Single doses as high as 20 mg have been studied, but severe supine hypertension occurs at a high rate (approximately 45%) at this dose 1
• Total daily doses greater than 30 mg have been tolerated but their safety and usefulness have not been systematically established 1
• Treatment should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1

Common Pitfalls to Avoid

• Do not start at lower doses (2.5 mg or 5 mg) in patients with normal renal function, as the FDA label and clinical trials support 10 mg as the effective starting dose 1, 4
• Monitor supine blood pressure regularly and discontinue if supine hypertension becomes excessive 1
• The therapeutic goal is to minimize postural symptoms, not to restore normotension 3, 2
• Midodrine should be used only after non-pharmacological measures (increased fluid/salt intake, compression garments, physical counter-maneuvers) have been attempted 3, 2

Expected Side Effects

• The most common adverse events are piloerection (goosebumps), pruritus, paresthesias, urinary retention, and chills 8
• Supine hypertension occurs in up to 25% of patients but can be minimized by proper timing of the last daily dose 8
• Scalp pruritus/tingling was reported in 13.5% of patients in clinical trials 5