What is the recommended dosing for midodrine (ProAmatine) in treating orthostatic hypotension?

Midodrine Dosing for Orthostatic Hypotension

The recommended dosing for midodrine (ProAmatine) in treating orthostatic hypotension is 10 mg three times daily, administered during daytime hours when the patient needs to be upright. 1

Dosing Schedule and Administration

• Standard dosing: 10 mg three times daily 1, 2
• Timing: Doses should be given at approximately 4-hour intervals during daytime hours 1
  • Suggested schedule: morning (upon arising), midday, and late afternoon (not later than 6 PM) 1
  • Can be given at 3-hour intervals if needed to control symptoms, but not more frequently 1
• Maximum daily dose: 30 mg total daily dose is the established safe limit 1
• Last dose timing: Should not be given after the evening meal or less than 4 hours before bedtime to reduce the risk of supine hypertension 1

Special Populations

• Renal impairment: Start with 2.5 mg doses in patients with abnormal renal function 1
• Elderly patients: No dose modifications necessary for patients 65 or older 1
• Gender considerations: No dose adjustments needed based on gender 1

Dose Titration and Efficacy

The efficacy of midodrine is dose-dependent, with a significant linear relationship between dosage and mean systolic blood pressure 3. Clinical studies have shown:

• 10 mg dose significantly increases standing systolic blood pressure, with peak effect at 1 hour 3
• Significant improvement in orthostatic symptoms compared to placebo 4, 5
• The 10 mg dose increases standing systolic blood pressure by approximately 22 mmHg (28%) 5

Monitoring and Safety Considerations

• Blood pressure monitoring: Regularly monitor both supine and standing blood pressure 6, 2
• Discontinuation criteria: Stop midodrine if supine blood pressure increases excessively 1
• Duration of action: The active metabolite (desglymidodrine) has a half-life of approximately 4 hours, supporting the three-times-daily dosing schedule 3

Common Side Effects

• Piloerection (scalp tingling/itching) - most common (13.5%) 5
• Supine hypertension (8%) 5
• Urinary retention or urgency (4%) 5
• Gastrointestinal disorders 7

Clinical Pearls

• The therapeutic goal is to minimize postural symptoms rather than restore normotension 2
• Single doses as high as 20 mg have been given but cause severe and persistent supine hypertension in about 45% of patients 1
• Consider combining midodrine with non-pharmacological approaches (compression garments, increased salt/fluid intake, physical counter-pressure maneuvers) for optimal management 6, 2
• Midodrine should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1

Alternative Medications

If midodrine is not effective or not tolerated, consider:

• Fludrocortisone (0.05-0.1 mg daily, titrated to 0.1-0.3 mg daily) 6, 2
• Droxidopa (100-600 mg three times daily) 6, 2