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

Maximum Daily Dose of Midodrine

The maximum daily dose of midodrine is 30 mg per day (10 mg three times daily), as explicitly stated by the FDA-approved labeling, though total daily doses greater than 30 mg have been tolerated by some patients but lack systematic safety and efficacy data. 1

FDA-Approved Maximum Dosing

• The FDA label clearly states that the recommended dose is 10 mg three times daily, with total daily doses greater than 30 mg having been tolerated but not systematically studied or established for safety and usefulness 1
• Single doses as high as 20 mg have been administered, but severe and persistent supine hypertension occurs at a high rate (approximately 45%) at this dose level 1
• The American Diabetes Association aligns with this recommendation, suggesting a maximum of 10 mg three times daily for orthostatic hypotension with careful monitoring for supine hypertension 2

Dosing Intervals and Timing Restrictions

• Doses should be spaced approximately 4 hours apart during daytime hours when the patient needs to be upright 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 and not after the evening meal to reduce the risk of supine hypertension during sleep 1
• A suggested schedule is: upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1

Dose-Limiting Adverse Effects

• Supine hypertension is the primary dose-limiting adverse effect, occurring in 22% of patients at 10 mg doses and escalating to 45% at 20 mg doses 2
• The risk of supine hypertension can be reduced by adhering to the 4-hour pre-bedtime cutoff for the final dose 3
• Treatment should be discontinued if supine blood pressure increases excessively 1

Special Population Considerations

Hepatorenal Syndrome Exception: Higher dosing of 12.5 mg three times daily (37.5 mg total daily) has been used in combination with octreotide for hepatorenal syndrome, as recommended by the American Association for the Study of Liver Diseases 2

Renal Impairment: Patients with abnormal renal function should initiate treatment at 2.5 mg doses due to renal excretion of the active metabolite desglymidodrine 1

Hemodialysis Patients: May use 5-10 mg administered 30 minutes before dialysis, as midodrine is removed by dialysis 4, 2

Critical Safety Monitoring

• Monitor supine and standing blood pressure regularly, and discontinue if supine hypertension develops 1
• Watch for reflex bradycardia, particularly in patients taking beta-blockers, digoxin, or non-dihydropyridine calcium channel blockers 4, 2
• Continue midodrine only in patients who demonstrate symptomatic improvement during initial treatment 1

Common Pitfall to Avoid

Do not exceed 30 mg total daily dose (10 mg TID) in routine orthostatic hypotension management, as doses above this threshold lack established safety profiles and carry substantially increased risk of severe supine hypertension 1. The American College of Cardiology suggests considering cardiology consultation for off-label dosing at 15 mg three times daily 2.