Midodrine for Orthostatic Hypotension Management
Midodrine is recommended at a dosage of 10 mg three times daily for the treatment of symptomatic orthostatic hypotension, with the last dose taken at least 4 hours before bedtime to minimize the risk of supine hypertension. 1, 2
Mechanism and Indication
Midodrine is a prodrug that is converted to desglymidodrine, an alpha-1 adrenergic agonist that increases vascular tone and elevates blood pressure by activating alpha-adrenergic receptors in arteriolar and venous vasculature. 1
- FDA-approved specifically for treating symptomatic orthostatic hypotension
- Increases standing systolic blood pressure by approximately 15-30 mmHg at 1 hour after a 10 mg dose
- Effects persist for 2-3 hours after administration
- Does not significantly affect heart rate in patients with autonomic failure 1
Dosing Protocol
- Starting dose: 10 mg three times daily 2, 3
- Timing: First dose in the morning before getting out of bed, with subsequent doses at approximately 4-hour intervals
- Last dose: Should be taken no later than 4 hours before bedtime to minimize supine hypertension 1, 4
- Renal impairment: Start with 2.5 mg in patients with renal dysfunction 1
Clinical Evidence
Midodrine has demonstrated significant efficacy in multiple controlled trials:
- In a randomized, double-blind multicenter study with 171 patients, midodrine 10 mg three times daily significantly improved standing systolic BP (p<0.001) and symptoms of orthostatic hypotension including lightheadedness by the second week of treatment 3
- Another double-blind, placebo-controlled study with 97 patients showed midodrine 10 mg increased standing systolic blood pressure by 22 mmHg (28%, p<0.001 vs placebo) and improved symptoms including dizziness, weakness, syncope, and low energy levels 5
- According to the American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines, midodrine has a Class IIa recommendation with Level B-R evidence for patients with recurrent vasovagal syncope with no history of hypertension, heart failure, or urinary retention 6
Monitoring and Precautions
- Blood pressure monitoring: Evaluate for supine and sitting hypertension at the beginning of therapy and regularly thereafter 1
- Supine hypertension: Occurs in up to 25% of patients; can be managed by elevating the head of the bed during sleep 1, 4
- Urinary retention: Use cautiously in patients with urinary retention problems as desglymidodrine acts on alpha-adrenergic receptors of the bladder neck 1
- Drug interactions: Use with caution when combined with:
- Other vasoconstrictors (phenylephrine, ephedrine, pseudoephedrine)
- Cardiac glycosides
- Beta-blockers
- MAO inhibitors (avoid concomitant use)
- Alpha-adrenergic blockers (can antagonize midodrine's effects) 1
Non-Pharmacological Management
Before or alongside midodrine therapy, implement these measures:
- Acute water ingestion (Class I recommendation, Level B-R evidence) 2
- Physical counter-pressure maneuvers like leg crossing and squatting (Class IIa recommendation) 2
- Compression garments including abdominal binders and waist-high support stockings 2
- Increased salt and fluid intake (targeting 2-3 liters daily) unless contraindicated 2
- Elevation of the head of bed during sleep with 4-6 inch blocks 6, 2
- Regular exercise to prevent deconditioning 2
Treatment Goals
The primary therapeutic goal is to minimize postural symptoms rather than restore normotension completely. Midodrine therapy should be continued only for patients who report significant symptomatic improvement. 2, 1
Common Side Effects
- Piloerection (goosebumps)
- Pruritus (itching)
- Paresthesias
- Urinary retention
- Chills
- Supine hypertension 1, 4, 5
Midodrine is a well-tolerated and effective option for managing orthostatic hypotension when used appropriately with careful monitoring for supine hypertension.