What is the maximum recommended dose of midodrine (alpha-adrenergic agonist) for treating orthostatic hypotension?

Maximum Midodrine Dose

The maximum recommended dose of midodrine is 10 mg three times daily (total daily dose of 30 mg), with doses spaced approximately 4 hours apart during daytime hours and the last dose given no later than 6 PM to avoid supine hypertension during sleep. 1

Standard Dosing Parameters

The FDA-approved dosing regimen establishes clear upper limits:

• Maximum single dose: 10 mg 1
• Maximum daily dose: 30 mg (10 mg three times daily) 1
• Dosing interval: Approximately 4-hour intervals, or 3-hour intervals if needed to control symptoms 1
• Last dose timing: Not later than 6 PM or at least 4 hours before bedtime 1

Higher Doses and Associated Risks

While single doses as high as 20 mg have been administered in clinical studies, this practice carries significant risks:

• Severe supine hypertension occurs in approximately 45% of patients at 20 mg single doses 1
• At 10 mg doses, supine systolic pressure ≥200 mmHg occurred in 22% of patients 1
• At 20 mg doses, supine systolic pressure ≥200 mmHg occurred in 45% of patients, with elevated pressures often lasting 6 hours or more 1
• Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been systematically studied or established 1

Special Population Adjustments

Renal impairment: Treatment should be initiated at 2.5 mg doses due to renal excretion of the active metabolite desglymidodrine 1

Hepatorenal syndrome: Higher dosing is used, starting at 7.5 mg three times daily and titrating to 12.5 mg three times daily in combination with octreotide 2

Hemodialysis patients: Midodrine is removed by dialysis; doses of 5-10 mg can be given 30 minutes before dialysis sessions 2, 1

Clinical Evidence Supporting 10 mg Three Times Daily

The 10 mg three times daily regimen is supported by multiple high-quality studies:

• A dose-response study demonstrated that 10 mg doses produced standing systolic pressure increases of approximately 30 mmHg at 1 hour, with effects sustained for 2 hours 3
• The half-life of the active metabolite desglymidodrine is approximately 3-4 hours, supporting three-times-daily dosing 1, 3
• A multicenter randomized controlled trial of 171 patients confirmed that 10 mg three times daily significantly improved standing systolic blood pressure and symptoms 4
• A Phase 4 confirmatory study demonstrated clinical benefit with increased time to syncopal symptoms (521 seconds longer than placebo, p=0.0131) 5

Critical Safety Considerations

Supine hypertension monitoring is mandatory: The supine and standing blood pressure should be monitored regularly, and midodrine should be stopped if supine blood pressure increases excessively 1

Timing restrictions are essential: 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

Treatment continuation criteria: Midodrine should only be continued in patients who demonstrate symptomatic improvement during initial treatment 1