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

Recommended Dosing of Midodrine for Orthostatic Hypotension

The recommended dose of midodrine for orthostatic hypotension is 10 mg three times daily, administered during daytime hours when the patient needs to be upright. 1

Dosing Schedule and Administration

• Initial dosing:

  • Start with 10 mg three times daily
  • Administer at approximately 4-hour intervals: morning (upon arising), midday, and late afternoon (not later than 6 PM) 1
  • If needed, doses may be given at 3-hour intervals, but not more frequently 1

• Timing considerations:

  • Do not give after the evening meal or less than 4 hours before bedtime to reduce the risk of supine hypertension 1
  • Schedule doses during daytime hours when the patient needs to be upright for daily activities 2

• Dose adjustments:

  • For patients with renal impairment: Start with 2.5 mg doses and titrate cautiously 1
  • For elderly patients: No specific dose adjustments needed based on age 1

Efficacy and Monitoring

• Midodrine typically increases standing systolic blood pressure by 15-30 mmHg at 1 hour after a 10 mg dose, with effects persisting for 2-3 hours 1
• Clinical trials have demonstrated that 10 mg three times daily significantly improves standing systolic blood pressure and symptoms of orthostatic hypotension 3, 4
• Regular monitoring of supine and standing blood pressure is essential 1
• Continue midodrine only in patients who demonstrate symptomatic improvement during initial treatment 1

Precautions and Contraindications

• Maximum dosing:

  • Total daily doses greater than 30 mg have been tolerated but safety and efficacy not established 1
  • Single doses as high as 20 mg have been used but cause severe and persistent supine hypertension in about 45% of patients 1

• Contraindications:

  • Avoid in patients with severe cardiac disease, acute renal disease, urinary retention, pheochromocytoma, or thyrotoxicosis 2
  • Do not use in patients with supine hypertension (>180/110 mmHg) 1

Common Side Effects

• Piloerection (goosebumps) and scalp tingling/pruritus (13.5% of patients) 5
• Supine hypertension (8% of patients) 5
• Urinary urgency or retention (4% of patients) 5
• Gastrointestinal disturbances 6

Treatment Algorithm

1. Before starting midodrine:

   • Implement non-pharmacological measures first (increased salt/fluid intake, compression garments, physical counter-maneuvers) 2
   • Identify and discontinue medications that may exacerbate orthostatic hypotension 2

2. Initiate midodrine therapy:

   • Standard patients: 10 mg three times daily 1
   • Renal impairment: 2.5 mg three times daily, titrate as tolerated 1

3. Monitor effectiveness:

   • Assess standing blood pressure 1 hour after dosing 1
   • Evaluate symptom improvement (dizziness, lightheadedness, syncope) 5
   • Check for supine hypertension 1

4. Adjust as needed:

   • If inadequate response: Consider shortening interval to every 3 hours 1
   • If excessive supine hypertension: Reduce dose or discontinue 1

5. Consider combination therapy if needed:

   • Midodrine can be combined with fludrocortisone (0.1-0.3 mg daily) for enhanced effect in refractory cases 2

Remember that the therapeutic goal is to minimize postural symptoms rather than to restore normotension completely 2. Midodrine is the only medication approved by the FDA for the treatment of symptomatic orthostatic hypotension 2.