What is the maximum dose of midodrine (alpha-adrenergic agonist) per day?

Maximum Dose of Midodrine

The maximum daily dose of midodrine is 30 mg, typically administered as 10 mg three times daily, with the last dose taken no later than 6 PM to reduce the risk of supine hypertension during sleep. 1

Dosing Guidelines

• Standard dosing regimen: 10 mg three times daily 1
• Dosing intervals:
  • Approximately 4-hour intervals (preferred)
  • Can be given at 3-hour intervals if needed for symptom control, but not more frequently 1
• Timing considerations:
  • Morning dose: Shortly before or upon arising
  • Midday dose: Around noon
  • Afternoon dose: Late afternoon (not later than 6 PM) 1
  • Last dose should be at least 4 hours before bedtime 2

Safety Considerations

• Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (approximately 45%) at this dose 1
• While total daily doses greater than 30 mg have been tolerated by some patients, their safety and usefulness have not been systematically studied or established 1
• In exceptional cases, higher doses (up to 90 mg daily) have been reported in case studies for specific situations like treprostinil-induced hypotension in hemodialysis patients, but this is far outside standard practice and not recommended without specialist supervision 3

Special Populations

• Renal impairment: Start with lower doses (2.5 mg) in patients with abnormal renal function since desglymidodrine (the active metabolite) is excreted renally 1
• Elderly patients: No dose modifications necessary based on age, as blood levels of midodrine and desglymidodrine were similar when comparing patients 65 or older vs. younger than 65 1
• Gender considerations: No dose modifications necessary based on gender 1

Monitoring Requirements

• Regular monitoring of supine and standing blood pressure is essential 1
• Discontinue midodrine if supine blood pressure increases excessively 1
• Continue treatment only in patients who demonstrate symptomatic improvement during initial treatment 1

Pharmacokinetic Considerations

• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the active metabolite desglymidodrine 4
• The half-life of desglymidodrine is approximately 4 hours, supporting the standard 3-4 hour dosing interval 5
• Some research suggests that a 6-hour dosing frequency may be appropriate in certain clinical settings 6, but the FDA-approved dosing remains at 3-4 hour intervals 1

Common Side Effects

• Piloerection (goosebumps)
• Pruritus (itching)
• Paresthesias
• Urinary retention
• Chills 4
• Supine hypertension (occurs in up to 25% of patients) 4

By adhering to the maximum daily dose of 30 mg and following the recommended dosing schedule, the risk of adverse effects can be minimized while maximizing therapeutic benefit for patients requiring midodrine therapy.