What is the recommended treatment for orthostatic hypotension using Midodrine?

Recommended Treatment for Orthostatic Hypotension Using Midodrine

Midodrine is a first-line pharmacological treatment for symptomatic orthostatic hypotension, with a recommended dosing of 2.5-10mg three times daily, when non-pharmacological measures fail to adequately control symptoms. 1, 2

Treatment Algorithm

Step 1: Non-Pharmacological Measures (First-Line)

• Increase fluid intake to 2-3 liters daily and salt consumption to 6-9g daily, if not contraindicated by other conditions 1
• Implement physical counter-maneuvers (leg-crossing, muscle tensing, squatting, stooping) during symptom onset 1
• Use compression garments, including thigh-high and abdominal compression 1
• Elevate the head of the bed during sleep to prevent supine hypertension 1
• Acute water ingestion (≥480 mL) for temporary relief, with peak effect at 30 minutes 1
• Recommend smaller, more frequent meals to reduce post-prandial hypotension 1

Step 2: Pharmacological Treatment with Midodrine

• Initiate midodrine at 2.5-5mg three times daily 1, 3
• Titrate dose up to 10mg three times daily as needed 2, 4
• Schedule doses to avoid supine hypertension: take the last dose no later than 6 PM (at least 3-4 hours before bedtime) 1, 3
• Expect standing systolic BP to increase by 15-30 mmHg at 1 hour after a 10mg dose, with effects persisting for 2-3 hours 3, 4

Mechanism and Pharmacokinetics

• Midodrine is a prodrug that forms the active metabolite desglymidodrine, an alpha1-agonist 3
• Peak plasma levels of midodrine occur after 30 minutes, with a half-life of approximately 25 minutes 3
• Desglymidodrine reaches peak blood concentrations 1-2 hours after dosing with a half-life of 3-4 hours 3, 4
• The absolute bioavailability of midodrine (measured as desglymidodrine) is 93% and is not affected by food 3

Monitoring and Precautions

• Evaluate for supine hypertension at treatment initiation - midodrine can cause marked elevation of supine blood pressure (>200 mmHg systolic) 3
• Monitor blood pressure carefully when midodrine is used with other vasoconstrictors 3
• Use with caution in patients with urinary retention problems, as desglymidodrine acts on alpha-adrenergic receptors of the bladder neck 3
• Use with caution in patients with renal impairment, with a starting dose of 2.5mg 3
• Assess renal and hepatic function prior to initiating therapy 3

Special Considerations

• The therapeutic goal is minimizing postural symptoms rather than restoring normotension 1, 2
• For non-responders to monotherapy, consider combination therapy with midodrine and fludrocortisone 1
• Avoid concomitant use with MAO inhibitors or linezolid 3
• Alpha-adrenergic blocking agents (prazosin, terazosin, doxazosin) can antagonize midodrine's effects 3
• Midodrine is removed by dialysis in patients undergoing hemodialysis 3

Common Adverse Effects

• Piloerection, pruritus, paresthesias, urinary retention, and chills 5, 6
• Supine hypertension (reported in up to 25% of patients) 5, 7
• Slight slowing of heart rate due to vagal reflex 3

Clinical Evidence

• Multiple randomized controlled trials have demonstrated that midodrine significantly improves standing systolic blood pressure and symptoms of orthostatic hypotension 6, 7, 8
• A dose-response study showed a significant linear relationship between midodrine dosage and mean systolic blood pressure, with 10mg being an effective dose 4