What is the recommended treatment and dosage for orthostatic hypotension using midodrine?

Treatment of Orthostatic Hypotension with Midodrine

Midodrine is recommended at a dosage of 10 mg three times daily for the treatment of symptomatic orthostatic hypotension, with doses administered during daytime hours when upright posture is needed. 1, 2

First-Line Treatment Options

• Midodrine is a first-line pharmacological treatment for neurogenic orthostatic hypotension, acting as a peripheral selective α1-adrenergic agonist that exerts a pressor effect through arteriolar constriction and venoconstriction of capacitance vessels 2
• The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guidelines give midodrine a Class IIa recommendation (Level of Evidence: B-R) for patients with syncope due to neurogenic orthostatic hypotension 2

Dosing Recommendations

• Initial dosing should follow this schedule:

  • Start with 10 mg three times daily, administered at approximately 4-hour intervals 1
  • Timing: shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
  • If needed, doses may be given at 3-hour intervals to control symptoms, but not more frequently 1

• Dose adjustments:

  • For patients with renal impairment: Start with 2.5 mg doses and titrate cautiously 1
  • Individual dose titration may be required, with doses up to 10-20 mg per dose shown to be effective 3
  • Total daily doses greater than 30 mg have been tolerated but are not systematically studied 1

Efficacy

• Midodrine increases standing systolic blood pressure by approximately 22 mmHg (28%) compared to placebo 4, 5
• Clinical studies demonstrate significant improvement in orthostatic symptoms including:
  • Dizziness/lightheadedness
  • Weakness/fatigue
  • Syncope
  • Low energy level
  • Impaired ability to stand 4, 5
• The peak effect occurs approximately 1 hour after administration, with a half-life of approximately 4 hours for the active metabolite desglymidodrine 3

Important Precautions

• To reduce the risk of supine hypertension:

  • Do not administer after the evening meal or less than 4 hours before bedtime 1
  • Monitor supine and standing blood pressure regularly 1
  • Discontinue treatment if supine hypertension increases excessively 1

• Midodrine should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1

• Use with caution in patients with:

  • History of hypertension
  • Heart failure
  • Urinary retention 2, 1

Common Side Effects

• Scalp pruritus/tingling (reported in 13.5% of patients) 4
• Piloerection (goosebumps) 1, 4
• Supine hypertension (reported in approximately 8% of patients) 4
• Urinary urgency or retention (reported in approximately 4% of patients) 4
• Bradycardia (due to reflex parasympathetic stimulation) 2

Complementary Non-Pharmacological Approaches

• Physical counter-pressure maneuvers (leg crossing, lower body muscle tensing) 2
• Compression garments (at least thigh-high, preferably including abdomen) 2
• Increased fluid intake (2-3 L per day) and salt intake (6-9 g per day) if not contraindicated 2
• Acute water ingestion (≥240 mL) for temporary relief, with peak effect at 30 minutes 2
• Head-up bed position during sleep 2

Alternative Pharmacological Options

• Fludrocortisone (0.1-0.3 mg daily) - acts through sodium retention and direct vessel constriction 2
• Droxidopa - improves symptoms of neurogenic OH due to Parkinson disease, pure autonomic failure, and multiple system atrophy 2
• Pyridostigmine - may be beneficial in patients refractory to other treatments 2
• Octreotide - may be beneficial in patients with refractory recurrent postprandial or neurogenic OH 2

Clinical Pearls and Pitfalls

• Midodrine is contraindicated in patients with severe cardiac disease, acute renal disease, urinary retention, pheochromocytoma, or thyrotoxicosis 1, 6
• Avoid concomitant use with other α-adrenergic agents (ephedrine, pseudoephedrine) as this may worsen supine hypertension 2
• Midodrine can antagonize the actions of α-adrenergic blockers (terazosin, prazosin, doxazosin) 2
• Treatment should focus on minimizing postural symptoms rather than restoring normotension 2
• Midodrine is effectively cleared by hemodialysis with a reduced half-life of 1.4 hours during dialysis 2