What is the recommended dosage and treatment approach for Midodrine (Midodrine) in managing orthostatic hypotension?

Midodrine Dosing and Treatment Approach for Orthostatic Hypotension

The recommended dosage of midodrine for orthostatic hypotension is 10 mg three times daily, taken at approximately 4-hour intervals during daytime hours when the patient needs to be upright and active. 1, 2

Dosing Schedule and Administration

• Initial dosing should begin with 10 mg three times daily, with a suggested schedule of: shortly before or upon arising in the morning, midday, and late afternoon (not later than 6 P.M.) 1
• Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently 1
• The last dose should be taken at least 4 hours before bedtime to reduce the risk of supine hypertension during sleep 1, 3
• For patients with renal impairment, treatment should be initiated with lower doses of 2.5 mg 1
• In dialysis patients, a single 5 mg dose administered 30 minutes before dialysis can improve intradialytic and postdialytic blood pressure 2

Dose Titration and Monitoring

• Dosing should be individually tailored based on patient response and tolerability 2, 4
• Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose 1
• Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been systematically established 1
• Supine and standing blood pressure should be monitored regularly, and midodrine should be discontinued if supine blood pressure increases excessively 1
• The therapeutic goal is to minimize postural symptoms rather than to restore normotension 3, 2

Treatment Algorithm

1. First-line approach: Non-pharmacological measures should be tried first 1, 2:

   • Increased fluid (2-3 liters daily) and salt intake (6-9g daily) if not contraindicated 3
   • Physical counter-maneuvers (leg-crossing, stooping, squatting, muscle tensing) 3
   • Compression garments for legs and abdomen 3
   • Gradual positional changes 3
   • Smaller, more frequent meals to reduce post-prandial hypotension 3
   • Elevating the head of the bed during sleep 3

2. Initiate midodrine when non-pharmacological measures fail to adequately control symptoms 3

3. Consider combination therapy for resistant orthostatic hypotension:

   • Midodrine may be combined with fludrocortisone for non-responders to monotherapy 3, 2
   • Other options include droxidopa, which is also FDA-approved for neurogenic orthostatic hypotension 3

Side Effects and Precautions

• Common side effects include piloerection (goosebumps), scalp pruritus/tingling, and urinary urgency 2, 5, 6
• Supine hypertension occurs in approximately 8% of patients 6
• Use cautiously in patients with:
  • Congestive heart failure 2
  • Patients using other negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) 2
• Avoid concomitant use with other alpha-adrenergic agents as this may aggravate supine hypertension 2
• Midodrine can antagonize the actions of alpha-adrenergic blockers (terazosin, prazosin, doxazosin) and could result in urinary retention 2

Clinical Efficacy

• Midodrine is the only medication FDA-approved specifically for the treatment of symptomatic orthostatic hypotension 2, 1
• It increases standing systolic blood pressure by approximately 15-30 mmHg for 2-3 hours 3, 7
• The peak effect occurs approximately 1 hour after administration 4
• The half-life of the active metabolite desglymidodrine is approximately 4 hours, supporting the three-times-daily dosing schedule 4

Important Considerations

• Midodrine should be continued only in patients who demonstrate symptomatic improvement during initial treatment 1
• Midodrine should be used in patients whose lives are considerably impaired despite standard clinical care 1
• The drug has minimal cardiac and central nervous system effects due to its specificity for peripheral alpha-receptors 2