Maximum Dose of Midodrine
The maximum recommended dose of midodrine is 10 mg three times daily for orthostatic hypotension, with total daily doses not exceeding 30 mg, though doses above 30 mg have been tolerated but lack systematic safety data. 1
FDA-Approved Dosing Parameters
- The FDA label specifies that the standard recommended dose is 10 mg three times daily, administered during daytime hours when the patient needs to be upright 1
- Single doses as high as 20 mg have been given, but severe and persistent supine hypertension occurs at a high rate (approximately 45%) at this dose 1
- Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established 1
Dosing Schedule and Timing Restrictions
- Doses should be given approximately 4 hours apart during daytime hours: shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
- Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently 1
- The final daily dose must be taken at least 4 hours before bedtime to reduce the risk of supine hypertension during sleep 2, 1
- Midodrine should not be given after the evening meal 1
Titration Strategy
- Start with 2.5-5 mg three times daily and titrate upward based on blood pressure response and symptom improvement 2
- The dose can be gradually increased to the maximum of 10 mg three times daily 2
- Peak blood pressure elevation occurs at 1 hour post-dose with a duration of action of 2-4 hours 2, 3
Critical Safety Considerations
- Supine hypertension is the primary dose-limiting adverse effect, occurring in 22% of patients at 10 mg doses and 45% at 20 mg doses 2, 1
- Standing and supine blood pressure should be monitored regularly, and midodrine should be discontinued if supine blood pressure increases excessively 1
- Treatment should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1
Special Population Adjustments
- For patients with abnormal renal function, initiate treatment at 2.5 mg doses, as desglymidodrine is excreted renally 1
- For hemodialysis patients, use 5-10 mg administered 30 minutes before dialysis, as midodrine is removed by dialysis 2
- For hepatorenal syndrome specifically, higher dosing of 7.5 mg three times daily titrated to 12.5 mg three times daily may be used in combination with octreotide 2
Evidence Supporting Maximum Dosing
- Multiple randomized controlled trials have demonstrated efficacy at 10 mg three times daily, with significant improvements in standing systolic blood pressure (22-27 mmHg increase) and symptom relief 4, 5, 6
- A dose-response study confirmed a linear relationship between midodrine dosage and systolic blood pressure increase, with 10 mg being the optimal balance of efficacy and safety 3
- A 2016 Phase 4 study confirmed clinical benefit with midodrine at standard dosing, showing an additional 521 seconds of tilt-table tolerance compared to placebo 7