What is the comparison between midodrine and droxidopa for treating orthostatic hypotension?

Droxidopa vs Midodrine for Orthostatic Hypotension

Both droxidopa and midodrine are FDA-approved for treating orthostatic hypotension, with midodrine being the preferred first-line pharmacologic agent due to its established efficacy and safety profile. 1

Comparison of Medications

Mechanism of Action

• Midodrine: Alpha-1 adrenergic agonist that causes peripheral vasoconstriction 1
• Droxidopa: Synthetic amino acid that converts to norepinephrine, increasing blood pressure 1

Dosing

• Midodrine: 10 mg up to 2-4 times daily 1

  • Peak effect at 1 hour after administration 2
  • Half-life of active metabolite (desglymidodrine) is approximately 4 hours 2
  • Last dose should be taken at least 4 hours before bedtime to reduce risk of supine hypertension 3

• Droxidopa: 100-600 mg three times daily, with last dose at least 4 hours before bedtime 1

Efficacy

• Midodrine has been shown to:

  • Significantly increase standing systolic blood pressure compared to placebo 4, 2
  • Improve standing time and energy levels 3
  • Reduce clinical symptoms including dizziness, lightheadedness, and syncope 3, 5
  • Show a linear dose-response relationship with mean systolic blood pressure 2

• Droxidopa is specifically FDA-approved for neurogenic orthostatic hypotension 1

Treatment Algorithm

1. Start with non-pharmacological approaches:

   • Physical counter-pressure maneuvers
   • Compression garments
   • Increased salt and fluid intake
   • Small frequent meals
   • Elevating head of bed during sleep
   • Regular exercise to prevent deconditioning 1

2. If non-pharmacological measures are insufficient, initiate pharmacological therapy:

   • First-line: Midodrine 10 mg three times daily
   • Monitor for efficacy and adjust dosage as needed (2.5-10 mg per dose)
   • Ensure last dose is taken at least 4 hours before bedtime

3. Consider droxidopa if:

   • Patient has neurogenic orthostatic hypotension
   • Inadequate response to midodrine
   • Intolerable side effects with midodrine

Side Effects and Precautions

Midodrine

• Most common side effects: piloerection, pruritus, paresthesias, urinary retention, and chills 3
• Risk of supine hypertension (up to 25% of patients) 3
• Generally well-tolerated with mild adverse effects that can be controlled by reducing dosage 6

Both Medications

• Monitor for supine hypertension
• Regular blood pressure measurements in both supine and standing positions
• Avoid medications that can worsen orthostatic hypotension (opioids, anticholinergics, tricyclic antidepressants) 1

Clinical Pearls

• The therapeutic goal is to minimize postural symptoms rather than to restore normotension 7, 1
• Regular follow-up every 3 months once stabilized is recommended 1
• Patient education about recognizing prodromal symptoms is important for preventing episodes 1
• Midodrine has been shown to be at least as effective as other sympathomimetic agents with fewer and less severe adverse effects 6