Midodrine As-Needed Dosing for Orthostatic Hypotension
Midodrine is not recommended for as-needed use; it should be administered on a scheduled basis at 10 mg three times daily during daytime hours when upright activity is required, with doses spaced approximately 3-4 hours apart and the last dose no later than 6 PM to avoid supine hypertension. 1
Standard Dosing Regimen
The FDA-approved dosing schedule for midodrine is 10 mg three times daily, administered during daytime hours when the patient needs to be upright and pursuing activities of daily living 1. The recommended timing is:
- Shortly before or upon arising in the morning
- Midday
- Late afternoon (not later than 6 PM) 1
Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently 1. The critical restriction is that midodrine should not be given after the evening meal or less than 4 hours before bedtime to reduce the risk of supine hypertension during sleep 1.
Dose Titration Strategy
Initial dosing should start at 2.5-5 mg three times daily and be gradually titrated upward to 10 mg three times daily based on blood pressure response and symptom improvement 2. This titration approach is supported by clinical trial data showing:
- The 10 mg dose produces a 22-30 mmHg increase in standing systolic blood pressure at 1 hour post-dose 3, 4, 5
- Peak blood pressure effects occur at 1 hour, with some effect persisting for 2-3 hours 1
- The active metabolite (desglymidodrine) has a half-life of approximately 3-4 hours 1, 5
Why Not As-Needed Dosing?
The pharmacokinetic profile of midodrine makes scheduled dosing essential rather than as-needed use:
- Midodrine requires approximately 30 minutes to reach peak prodrug levels and 1-2 hours for the active metabolite to reach peak concentrations 1
- The duration of action is only 2-4 hours, necessitating multiple daily doses for sustained symptom control 1
- Clinical trials demonstrating efficacy used scheduled three-times-daily dosing, not as-needed administration 3, 4, 5
Special Dosing Considerations
For patients with renal impairment, initiate treatment at 2.5 mg doses due to renal excretion of the active metabolite 1. Approximately 80% of desglymidodrine is eliminated by active renal secretion 1.
For hemodialysis patients, midodrine is removed by dialysis and may be used at 5-10 mg doses to prevent intradialytic hypotension 2, 1.
Single doses as high as 20 mg have been studied, but severe supine hypertension occurs at a high rate (approximately 45%) at this dose 1. The 20 mg dose produced sustained blood pressure elevation for up to 4 hours but with unacceptable rates of supine systolic pressures ≥200 mmHg 5.
Critical Safety Monitoring
Supine and standing blood pressure must be monitored regularly, and midodrine should be discontinued if supine blood pressure increases excessively 1. The risk of supine hypertension can affect up to 25% of patients but is significantly reduced by avoiding evening doses 6.
Common adverse effects include piloerection (13.5%), pruritus, paresthesias, urinary retention (4%), and supine hypertension (8%) 6, 4. These are generally mild to moderate in severity 4.