What is the maximum recommended dose and frequency of midodrine (prodrug, converts to desglymidodrine) for the treatment of orthostatic hypotension?

Midodrine Maximum Dose and Frequency

The maximum recommended dose of midodrine is 10 mg three times daily (total 30 mg/day), administered at approximately 4-hour intervals during daytime hours, with the last dose no later than 6 PM to prevent supine hypertension during sleep. 1

Standard Dosing Protocol

• Initial dose: Start with 10 mg three times daily, taken at approximately 4-hour intervals when the patient needs to be upright and active 2, 1
• Suggested schedule: Shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
• Minimum dosing interval: Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently 1

Maximum Dose Considerations

• Standard maximum: 10 mg three times daily (total 30 mg/day) is the recommended maximum for routine use 1
• Higher doses: Single doses as high as 20 mg have been administered, but severe and persistent systolic supine hypertension occurs at a high rate (approximately 45%) at this dose 1
• Total daily maximum: Doses greater than 30 mg/day have been tolerated by some patients, but their safety and usefulness have not been systematically studied or established 1

Critical Timing Restrictions

• Evening cutoff: Midodrine should not be given after the evening meal or less than 4 hours before bedtime to reduce the risk of supine hypertension during sleep 1
• Last dose timing: The final dose must be taken at least 3-4 hours before bedtime, and not later than 6 PM 3, 1

Special Population Dosing

Renal Impairment

• Initial dose: Start with 2.5 mg doses in patients with abnormal renal function, as desglymidodrine is excreted renally 1
• Titration: Dose cautiously upward based on response and tolerability 1

Hepatorenal Syndrome Context

• Alternative dosing: When used for hepatorenal syndrome-acute kidney injury (HRS-AKI), initiate at 7.5 mg and titrate upward to 12.5 mg three times daily, combined with octreotide 4

Hemodialysis Patients

• Single pre-dialysis dose: 5 mg administered 30 minutes before dialysis has been shown to improve intradialytic and postdialytic blood pressure 2
• Clearance consideration: Midodrine is effectively cleared by hemodialysis with a reduced half-life of 1.4 hours 2

Evidence Base for Dosing

• 10 mg three times daily: This dose demonstrated a 22 mmHg (28%) increase in standing systolic blood pressure with significant symptom improvement in the largest randomized controlled trial 5, 6
• Dose-response relationship: A significant linear relationship exists between midodrine dosage and mean systolic blood pressure, with peak effect at 1 hour post-dose 7
• Duration of action: The half-life of the active metabolite desglymidodrine is approximately 4 hours, supporting three-times-daily dosing 7

Monitoring and Safety

• Supine hypertension risk: This is the most important limiting factor and must be monitored regularly 3, 1
• Continuation criteria: Midodrine should only be continued in patients who demonstrate symptomatic improvement during initial treatment 1
• Blood pressure monitoring: Measure supine and standing blood pressure regularly, and discontinue if supine blood pressure increases excessively 1

Common Pitfalls to Avoid

• Do not administer after 6 PM: This significantly increases the risk of nocturnal supine hypertension 2, 3
• Do not exceed 10 mg per dose routinely: Higher single doses (20 mg) carry a 45% risk of severe supine hypertension 1
• Do not use in patients with severe supine hypertension: This is a contraindication to therapy 3
• Monitor for urinary retention: Particularly in patients with spinal cord injury or neurogenic bladder, as midodrine increases vesical sphincter tone through alpha-1 adrenergic effects 8