What are reasonable parameters for midodrine (alpha-1 adrenergic receptor agonist) dosing in treating orthostatic hypotension?

Midodrine Dosing Parameters for Orthostatic Hypotension

Midodrine should be individually tailored at a dose of 10 mg three times daily, with the first dose taken before arising and the last dose at least 4 hours before bedtime to avoid supine hypertension. 1

Dosing Recommendations

• Starting dose: 2.5-5 mg three times daily
• Target dose: Up to 10 mg three times daily
• Maximum daily dose: 30-40 mg (divided into 3-4 doses)
• Timing of doses:
  • First dose: Before arising from bed in the morning
  • Subsequent doses: At midday and late afternoon
  • Last dose: No later than 6 PM or at least 4 hours before bedtime 1, 2
• Dose titration: Increase by 2.5 mg increments weekly until desired response or maximum dose 3

Pharmacokinetic Parameters

• Onset of action: Within 1 hour
• Peak effect: 1-2 hours after administration
• Duration of action: 2-4 hours (with effects on standing blood pressure lasting up to 3-4 hours) 2, 4
• Half-life:
  • Midodrine (prodrug): 25 minutes
  • Desglymidodrine (active metabolite): 3-4 hours 2

Monitoring Parameters

• Blood pressure response:

  • Target: Increase in standing systolic BP by 15-30 mmHg at 1 hour post-dose 2
  • Monitor both standing and supine blood pressure

• Symptom improvement:

  • Reduction in dizziness/lightheadedness
  • Decreased syncope episodes
  • Improved ability to stand
  • Enhanced energy levels 5, 3

• Supine hypertension:

  • Monitor for supine systolic BP >180 mmHg
  • Occurs in up to 25% of patients 6
  • May require dose adjustment or timing modification

Precautions and Contraindications

• Avoid in patients with:

  • Severe cardiac disease
  • Acute renal failure
  • Urinary retention
  • Pheochromocytoma
  • Thyrotoxicosis
  • Pre-existing sustained supine hypertension >180/110 mmHg 2

• Use with caution in:

  • Patients with prostatic hypertrophy
  • Visual problems
  • Hepatic impairment

Common Adverse Effects

• Piloerection (goosebumps)
• Pruritus (scalp tingling/itching)
• Paresthesias
• Urinary retention or urgency
• Supine hypertension
• Bradycardia
• Gastrointestinal symptoms 1, 2, 3

Treatment Algorithm

1. First-line approach: Non-pharmacological measures

   • Identify and correct other causes of orthostatic hypotension
   • Avoid medications that exacerbate symptoms
   • Implement behavioral strategies (gradual position changes, physical counter-maneuvers)
   • Increase fluid and salt intake if not contraindicated
   • Use compression garments 1

2. If symptoms persist: Initiate midodrine therapy

   • Start at 2.5-5 mg three times daily
   • Titrate dose weekly by 2.5 mg increments
   • Aim for 10 mg three times daily if tolerated 3, 4

3. If response inadequate: Consider combination therapy

   • Add fludrocortisone (0.05-0.1 mg daily, titrated to 0.1-0.3 mg daily) 1
   • Consider other agents (droxidopa, erythropoietin) for refractory cases 1

4. If adverse effects occur:

   • Reduce dose or adjust timing of administration
   • Consider alternative agents

Remember that the therapeutic goal is to minimize postural symptoms rather than to restore normotension 1. Continue midodrine only in patients who report significant symptomatic improvement 2.