What is the appropriate dosing for midodrine (Proamatine) in a patient with orthostatic hypotension?

Midodrine Dosing for Orthostatic Hypotension

Start midodrine at 10 mg three times daily, taken at approximately 4-hour intervals during daytime hours when the patient needs to be upright, with the last dose no later than 6 PM and never within 4 hours of bedtime to prevent supine hypertension. 1

Standard Dosing Regimen

• Initial dose: 10 mg three times daily at 4-hour intervals (e.g., upon arising, midday, and late afternoon before 6 PM) 1, 2
• Doses may be given at 3-hour intervals if needed to control symptoms, but not more frequently 1
• Maximum single dose studied is 20 mg, though this causes severe supine hypertension in approximately 45% of patients 1
• Total daily doses above 30 mg have been tolerated but lack systematic safety data 1

Dose Adjustments for Special Populations

Renal impairment: Start at 2.5 mg doses due to renal excretion of the active metabolite desglymidodrine 1

Hemodialysis patients: A single 5 mg dose administered 30 minutes before dialysis improves intradialytic and postdialytic blood pressure, with the drug effectively cleared during dialysis (half-life reduced to 1.4 hours) 2

Critical Timing Considerations

• Never administer after the evening meal or within 4 hours of bedtime to minimize supine hypertension during sleep 1
• The drug peaks at 1 hour post-dose with a half-life of approximately 4 hours for the active metabolite desglymidodrine 3, 2
• Schedule doses around periods when the patient needs to be upright and active 1

Monitoring and Continuation Criteria

• Monitor supine and standing blood pressure regularly 1, 4
• Discontinue if supine blood pressure increases excessively 1
• Continue midodrine only in patients who demonstrate symptomatic improvement during initial treatment 1, 4
• The therapeutic goal is minimizing postural symptoms (lightheadedness, syncope, weakness), not restoring normotension 2, 4

Evidence for Efficacy

The 10 mg three-times-daily regimen increases standing systolic blood pressure by approximately 22 mm Hg (28% increase) and significantly improves symptoms including dizziness, weakness, syncope, and impaired ability to stand 5, 6. This dose demonstrates a significant linear dose-response relationship and represents the FDA-approved regimen 3, 1.

Common Side Effects

• Piloerection (goosebumps) is the most characteristic side effect, reported in approximately 13.5% of patients 2, 6
• Supine hypertension occurs in 8% at standard doses but 45% at 20 mg doses 6, 1
• Scalp pruritus/tingling (13.5%), urinary urgency/retention (4%), and gastrointestinal complaints 6, 2

Concurrent Non-Pharmacological Measures

Implement these measures alongside midodrine therapy 2, 4:

• Increase fluid intake to 2-2.5 liters daily (unless contraindicated by heart failure) 2
• Increase salt intake (unless contraindicated) 2
• Use compression garments over legs and abdomen 4
• Teach physical counter-pressure maneuvers 2
• Elevate head of bed by 10° during sleep 4

Drug Interactions and Precautions

• Use cautiously with beta-blockers, digoxin, and non-dihydropyridine calcium channel blockers due to negative chronotropic effects 2
• Avoid concomitant alpha-adrenergic agents as this aggravates supine hypertension 2
• Midodrine antagonizes alpha-blockers (terazosin, prazosin, doxazosin) and may cause urinary retention 2
• Use cautiously in patients with congestive heart failure 2