What is the recommended dosing for midodrine (ProAmatine) in the treatment of orthostatic hypotension?

Midodrine Dosing for Orthostatic Hypotension

The recommended dosing for midodrine (ProAmatine) in the treatment of orthostatic hypotension is 10 mg three times daily, with doses taken during daytime hours approximately 4 hours apart (morning, midday, and late afternoon - not after 6 PM). 1

Dosing Schedule and Administration

• Initial dosing should begin with 10 mg three times daily, taken at approximately 4-hour intervals during daytime hours when the patient needs to be upright and active 2, 1
• A suggested schedule is: 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
• 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

Dose Adjustments

• Dosing should be individually tailored based on patient response and tolerability 2
• Single doses as high as 20 mg have been given to patients, but severe and persistent supine hypertension occurs at a high rate (about 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 systematically established 1
• For patients with abnormal renal function, treatment should be initiated using 2.5 mg doses due to renal excretion of desglymidodrine (the active metabolite) 1

Dose-Response Relationship

• There is a significant linear relationship between midodrine dosage and mean systolic blood pressure response 3
• A 10 mg dose increases standing systolic blood pressure by approximately 22 mmHg (28%) compared to placebo 4
• The blood pressure effect peaks at approximately 1 hour after administration 3
• The half-life of desglymidodrine (the active metabolite) is approximately 4 hours, supporting the three-times-daily dosing schedule 3

Monitoring and Continuation

• Supine and standing blood pressure should be monitored regularly 1
• Midodrine should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1
• Treatment should be stopped if supine blood pressure increases excessively 1
• The therapeutic goal is to minimize postural symptoms rather than to restore normotension 2

Common Side Effects

• Supine hypertension (8% of patients) - the most serious adverse effect 4
• Scalp pruritus/tingling (13.5% of patients) - most frequent side effect 4
• Piloerection (goosebumps) 2
• Urinary retention or urgency (4% of patients) 4
• Gastrointestinal disorders 5

Important Considerations

• Midodrine is the only medication approved by the FDA for the treatment of symptomatic orthostatic hypotension 2
• Non-pharmacological measures should be tried first, including increased fluid and salt intake, physical counter-maneuvers, and compression garments 2
• The potential risks of midodrine should be weighed against its possible benefits, including the balance between increasing standing blood pressure and avoiding marked supine hypertension 2
• Midodrine has been shown to improve symptoms of orthostatic hypotension including dizziness/lightheadedness, weakness/fatigue, syncope, and low energy level 4, 6