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

Midodrine Dosing for Orthostatic Hypotension

The recommended dosing for midodrine in orthostatic hypotension is 10 mg three times daily, administered during daytime hours when the patient needs to be upright, with doses spaced approximately 4 hours apart (e.g., morning, midday, and late afternoon, not later than 6 PM). 1

Dosing Schedule and Administration

• Initial dosing:

  • Standard starting dose: 10 mg three times daily 2, 1
  • For patients with renal impairment: Start with 2.5 mg doses 1
  • For elderly patients: Consider starting at lower doses and titrating up 3

• Timing of administration:

  • First dose: Shortly before or upon arising in the morning
  • Second dose: Midday
  • Third dose: Late afternoon (not later than 6 PM)
  • Important: Do not administer after the evening meal or less than 4 hours before bedtime 1

• Dose adjustments:

  • Doses may be given in 3-hour intervals if needed to control symptoms, but not more frequently 1
  • Single doses up to 20 mg have been given but cause severe supine hypertension in about 45% of patients 1
  • Total daily doses greater than 30 mg have been tolerated but safety and efficacy not established 1

Monitoring and Continuation of Therapy

• Regular monitoring of supine and standing blood pressure is essential 1
• Continue therapy only in patients who demonstrate symptomatic improvement during initial treatment 1
• Discontinue if supine blood pressure increases excessively 1
• Evaluate treatment effectiveness based on symptom improvement rather than blood pressure normalization 3

Efficacy and Evidence

Midodrine has demonstrated significant efficacy in treating neurogenic orthostatic hypotension:

• Increases standing systolic blood pressure by approximately 22 mmHg (28%) compared to placebo 4
• Significantly improves symptoms including dizziness, lightheadedness, weakness, fatigue, and syncope 4
• Shows dose-dependent effect on blood pressure 2
• Is considered a first-line pharmacologic treatment for symptomatic orthostatic hypotension 2

Adverse Effects and Precautions

• Common adverse effects:

  • Supine hypertension (major concern)
  • Scalp tingling/pruritus
  • Piloerection (goosebumps)
  • Urinary retention or urgency 2, 5

• Special precautions:

  • Patients with spinal cord injury who void spontaneously may develop urologic adverse effects 5
  • Use with caution in patients with cardiac amyloidosis or restrictive physiology 2
  • Avoid in patients with severe cardiac disease, acute renal disease, urinary retention, pheochromocytoma, or thyrotoxicosis

Combination Therapy

• For severe cases unresponsive to midodrine alone, consider combination with:
  • Fludrocortisone (0.05-0.1 mg daily with individual titration to 0.1-0.3 mg daily) 2
  • Non-pharmacological measures (compression garments, increased salt/fluid intake) 2

Non-Pharmacological Management

Always combine midodrine therapy with non-pharmacological approaches:

• Physical counter-pressure maneuvers (leg crossing, squatting) 2
• Compression garments (at least thigh-high, preferably including abdomen) 2
• Increased salt and fluid intake if not contraindicated 2
• Gradual positional changes 2
• Elevated head of bed during sleep 3
• Moderate physical activity to prevent deconditioning 3

Algorithm for Treatment

1. Start with non-pharmacological measures
2. If symptoms persist, initiate midodrine at 10 mg three times daily during daytime hours
3. Monitor for symptom improvement and supine hypertension
4. If inadequate response and no excessive supine hypertension, consider increasing dose (not exceeding 30 mg/day)
5. For refractory cases, consider adding fludrocortisone or switching to droxidopa
6. Discontinue if no symptomatic improvement or if supine hypertension becomes problematic

Remember that the goal of treatment is to minimize postural symptoms rather than to restore normotension 2.