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

Midodrine Dosage for Orthostatic Hypotension

The recommended dosage of midodrine for orthostatic hypotension is 10 mg three times daily, with doses taken during daytime hours when upright posture is needed, approximately 4 hours apart, and with the last dose no later than 6 PM to avoid supine hypertension. 1

Dosing Schedule and Administration

• Initial dosing should begin at 10 mg three times daily, with a suggested schedule of: morning (upon arising), midday, and late afternoon (not later than 6 PM) 2, 1
• Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently 1
• For patients with abnormal renal function, treatment should be initiated at a lower dose of 2.5 mg 1
• The final daily dose should be taken at least 4 hours before bedtime to reduce the risk of supine hypertension 2, 1
• Midodrine should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1

Dose Titration and Adjustments

• Dosing should be individually tailored based on patient response 2
• Single doses as high as 20 mg have been given but are associated with a high rate (about 45%) of severe supine hypertension 1
• Total daily doses greater than 30 mg have been tolerated by some patients, but safety and efficacy have not been systematically established 1
• A dose-response study showed a significant linear relationship between midodrine dosage and mean systolic blood pressure, with 10 mg being an effective dose for most patients 3

Monitoring

• Regular monitoring of supine and standing blood pressure is essential 1
• Midodrine should be discontinued if supine blood pressure increases excessively 1
• The therapeutic goal is to minimize postural symptoms rather than to restore normotension 2

Efficacy

• Midodrine significantly increases standing systolic blood pressure compared to placebo (average increase of 22 mmHg or 28% with 10 mg dose) 4, 5
• Clinical symptoms of orthostatic hypotension including dizziness, light-headedness, weakness, fatigue, and syncope show significant improvement with midodrine treatment 4, 5
• The onset of action is rapid, with peak effects at approximately 1 hour after administration 3
• The half-life of desglymidodrine (the active metabolite) is approximately 4 hours, supporting the three-times-daily dosing regimen 3

Common Side Effects and Precautions

• Most common adverse effects include piloerection (goosebumps), pruritus (especially scalp tingling/itching), paresthesias, urinary retention, and chills 2, 6, 5
• Supine hypertension occurs in up to 25% of patients, which can be minimized by proper timing of doses 6
• Midodrine should not be used in patients with severe cardiac disease, acute renal disease, urinary retention, pheochromocytoma, or thyrotoxicosis 6

Combination Therapy

• Midodrine is often used as a first-line pharmacological treatment after non-pharmacological measures have been implemented 2
• Non-pharmacological measures that should be tried first or used concurrently include:
  • Adequate hydration and salt intake (2-3 L of fluids per day and 10 g of NaCl) 2
  • Physical counter-pressure maneuvers 2
  • Compression garments over legs and abdomen 2
  • Elevation of the head of the bed by 10° during sleep 2

Alternative Pharmacological Options

• Fludrocortisone (0.1-0.3 mg daily) may be used as an alternative or adjunct to midodrine 2
• Droxidopa is another FDA-approved medication for neurogenic orthostatic hypotension 2
• Other less frequently used treatments include pyridostigmine, octreotide, and erythropoietin for specific patient populations 2