What is the recommended midodrine (ProAmatine) regimen for managing orthostatic hypotension?

Midodrine Regimen for Orthostatic Hypotension

Midodrine should be administered at a dosage of 5-20 mg three times daily, with the last dose taken at least 4 hours before bedtime to minimize the risk of supine hypertension. 1, 2

Dosing Schedule and Titration

• Initial dose: Start with 2.5-5 mg three times daily
• Timing: Administer at approximately 8 AM, 1 PM, and 6 PM (with the last dose no later than 6 PM)
• Titration: Gradually increase to 10 mg three times daily as needed and tolerated
• Maximum dose: Up to 20 mg three times daily for refractory cases

The therapeutic effect typically occurs within 1 hour of administration and may persist for 2-3 hours, with peak blood concentrations of the active metabolite (desglymidodrine) reached 1-2 hours after dosing 2.

Monitoring Parameters

• Blood pressure: Monitor standing and supine BP regularly
  • Expected increase in standing systolic BP: 15-30 mmHg at 1 hour post-dose 2
  • Watch for supine hypertension (systolic BP >200 mmHg), which occurs in up to 25% of patients 2, 3
• Symptom improvement: Track dizziness, lightheadedness, and syncope frequency
• Urinary function: Monitor for urinary retention, especially in patients with spinal cord injury 4

Precautions and Contraindications

• Supine hypertension: Elevate head of bed 10° to reduce risk 5
• Timing restrictions: Last dose should be taken at least 4 hours before bedtime 2, 3
• Drug interactions: Use caution with:
  • Other vasoconstrictors (phenylephrine, ephedrine)
  • Cardiac glycosides
  • Beta-blockers
  • MAO inhibitors (avoid concomitant use) 2
• Special populations:
  • Renal impairment: Start with 2.5 mg dose and monitor closely 2
  • Urinary retention: Use with caution in patients with this history 2
  • Diabetic patients: Monitor closely 2

Combination Therapy

Midodrine can be combined with other treatments for orthostatic hypotension:

• Fludrocortisone (0.1-0.3 mg once daily)
• Adequate hydration (2-3 L of fluids daily)
• Salt intake (10g NaCl daily)
• Physical counterpressure maneuvers
• Compression stockings or abdominal binders 5, 1

Efficacy and Evidence

Randomized controlled trials have demonstrated that midodrine significantly improves standing systolic blood pressure by 22-30 mmHg compared to placebo, along with significant improvement in orthostatic symptoms including dizziness, lightheadedness, weakness, fatigue, and syncope 6, 7.

Common Pitfalls to Avoid

1. Supine hypertension: Always advise patients to avoid the supine position shortly after taking midodrine
2. Inadequate timing: Administering the last dose too close to bedtime increases risk of nocturnal hypertension
3. Urinary retention: May develop insidiously, particularly in patients with neurological conditions 4
4. Insufficient monitoring: Regular BP checks in both standing and supine positions are essential

Midodrine is generally well-tolerated, with the most common side effects being piloerection (goosebumps), pruritus, paresthesias, urinary retention, and chills 3, 7.