What is the maximum recommended dose of midodrine (proamatine) for orthostatic hypotension?

Maximum Recommended Dose of Midodrine for Orthostatic Hypotension

The maximum recommended dose of midodrine for orthostatic hypotension is 10 mg three times daily, with a maximum total daily dose of 30 mg. 1

Dosing Guidelines

• The FDA-approved standard dosing regimen is 10 mg three times daily, administered during daytime hours when the patient needs to be upright 1
• Doses should be given at approximately 4-hour intervals (e.g., morning, midday, and late afternoon - not later than 6 PM) 1
• If needed for symptom control, doses may be given at 3-hour intervals, but not more frequently 1
• Single doses as high as 20 mg have been administered in clinical studies, but resulted in severe and persistent supine hypertension in about 45% of patients 1, 2
• Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been systematically established 1

Titration and Administration

• For orthostatic hypotension, treatment typically starts at lower doses and is titrated upward:
  • Initial dose can start at 2.5-5 mg three times daily 3, 4
  • Dose can be gradually increased to 10 mg three times daily based on blood pressure response and symptom improvement 3, 5
• For hepatorenal syndrome, midodrine should be initiated at 7.5 mg and titrated upward to 12.5 mg three times daily (in combination with octreotide) 3
• Midodrine should be taken during daytime hours only, with the last dose no later than 6 PM to reduce the risk of supine hypertension during sleep 1
• The medication should not be given after the evening meal or less than 4 hours before bedtime 1

Special Populations

• In patients with renal impairment, dosing should be cautious with a recommended starting dose of 2.5 mg 1
• In elderly patients (≥65 years), no specific dose adjustments are necessary as blood levels are similar to those in younger patients 1
• In hemodialysis patients, midodrine is removed by dialysis and may be used at doses of 5-10 mg to prevent intradialytic hypotension 3

Monitoring and Safety

• Regular monitoring of supine and standing blood pressure is essential 1, 5
• Treatment should be discontinued if supine blood pressure increases excessively 1
• The most common side effects include:
  • Piloerection (goosebumps) and scalp tingling/pruritus (13.5% of patients) 4
  • Supine hypertension (8% of patients) 4
  • Urinary urgency (4% of patients) 4
• Midodrine should be used cautiously in patients with heart failure and those taking other negative chronotropic agents such as beta-blockers, digoxin, and non-dihydropyridine calcium channel blockers 3

Clinical Efficacy

• At the 10 mg dose, midodrine increases standing systolic blood pressure by approximately 15-30 mmHg at 1 hour after administration 1, 5
• The effect persists for 2-3 hours, with the active metabolite (desglymidodrine) having a half-life of 3-4 hours 1, 2
• Midodrine has been shown to significantly improve symptoms of orthostatic hypotension including dizziness, lightheadedness, weakness, fatigue, syncope, and low energy levels 4, 6

Remember that midodrine is a prodrug that is converted to its active metabolite desglymidodrine, which acts as an alpha-1 agonist to increase vascular tone and elevate blood pressure 1, 7.