What is the recommended dosage of midodrine (alpha-1 adrenergic receptor agonist) for orthostatic hypotension?

Midodrine Dosage for Orthostatic Hypotension

The recommended 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, with the last dose no later than 6 PM to avoid supine hypertension during sleep. 1

Standard Dosing Regimen

• Start with 10 mg three times daily at 4-hour intervals: upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
• Doses may be given at 3-hour intervals if needed to control symptoms, but not more frequently 1
• Total daily doses should not exceed 30 mg (three 10 mg doses), as higher doses have not been systematically studied for safety 1

Dose Adjustments

For Renal Impairment

• Begin with 2.5 mg doses in patients with abnormal renal function, as the active metabolite desglymidodrine is renally excreted 1
• Midodrine is removed by hemodialysis; for dialysis patients, a single 5 mg dose given 30 minutes before dialysis improves intradialytic and postdialytic blood pressure 2

Higher Doses (Use with Caution)

• Single doses up to 20 mg have been used, but severe supine hypertension occurs in approximately 45% of patients at this dose 1
• The 20 mg dose produces similar standing blood pressure increases as 10 mg (about 30 mmHg at 1 hour) but with prolonged duration (4 hours vs 2 hours) and significantly higher risk of supine hypertension 1, 3

Critical Timing Considerations

• Never administer after the evening meal or less than 4 hours before bedtime to reduce supine hypertension risk during sleep 1
• The first dose should be taken shortly before or upon arising in the morning 1
• Peak effect occurs at 1 hour post-dose, with some effect persisting for 2-3 hours after a 10 mg dose 1

Monitoring and Continuation Criteria

• Monitor supine and standing blood pressure regularly and discontinue if supine blood pressure increases excessively 1
• Continue midodrine only in patients who demonstrate symptomatic improvement during initial treatment 4, 1
• The therapeutic goal is to minimize postural symptoms, not to restore normotension 5, 4

Evidence Supporting This Dosing

The 10 mg three times daily regimen is supported by multiple randomized controlled trials demonstrating:

• Standing systolic blood pressure increases of 15-30 mmHg at 1 hour post-dose 1, 6
• Significant improvement in orthostatic symptoms including dizziness, lightheadedness, weakness, and syncope 6, 7
• A dose-response relationship showing 10 mg is effective while minimizing supine hypertension risk compared to 20 mg 3

Common Pitfalls to Avoid

• Do not dose too late in the day: Evening doses cause nocturnal supine hypertension, which can lead to end-organ damage 5, 1
• Do not start at full dose in renal impairment: The active metabolite accumulates, increasing adverse effect risk 1
• Do not continue without documented benefit: Midodrine carries risks (supine hypertension, urinary retention) that only justify use when symptomatic improvement is clear 1

Non-Pharmacological Measures (Should Be Implemented Concurrently)

• Increase fluid intake to 2-2.5 liters daily (unless contraindicated by heart failure) 2
• Increase salt intake unless contraindicated 5, 2
• Use compression garments over legs and abdomen 5, 2
• Teach physical counter-pressure maneuvers (leg-crossing, squatting, muscle tensing) 5, 2
• Elevate head of bed by 10 degrees during sleep 4

Side Effects

The most common adverse effects include:

• Piloerection (goosebumps) and scalp pruritus/tingling (13.5% of patients) 2, 7
• Supine hypertension (8% at 10 mg dose, 45% at 20 mg dose) 1, 7
• Urinary retention or urgency (4%) 5, 7
• Bradycardia and gastrointestinal symptoms 5