Midodrine Dosing for Symptomatic Orthostatic Hypotension
The recommended starting dose of midodrine is 10 mg three times daily, taken during daytime hours when upright activity is needed, with doses spaced approximately 4 hours apart and the last dose no later than 6 PM or at least 4 hours before bedtime to minimize supine hypertension risk. 1
Standard Dosing Regimen
Initial Dose and Timing
- Start with 10 mg orally three times daily during waking hours when the patient needs to be upright 1, 2
- Administer doses at approximately 4-hour intervals: upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
- Doses may be given at 3-hour intervals if needed to control symptoms, but not more frequently 1
- Never administer after the evening meal or less than 4 hours before bedtime to reduce supine hypertension risk during sleep 1
Dose Titration
- The 10 mg dose three times daily is the most effective regimen, producing a 22-28 mm Hg (27-28%) increase in standing systolic blood pressure 3, 4
- Single doses up to 20 mg have been studied, but severe supine hypertension occurs in approximately 45% of patients at this dose 1
- Total daily doses greater than 30 mg have been tolerated but lack systematic safety and efficacy data 1
- A dose-response relationship exists, with 10 mg showing optimal balance between efficacy and tolerability 4
Dose Adjustments for Special Populations
Renal Impairment
- Start with 2.5 mg doses in patients with abnormal renal function, as the active metabolite desglymidodrine is renally excreted 1
- Titrate cautiously based on blood pressure response and tolerability 1
Hepatic Impairment
- The FDA label does not specify dose adjustments for hepatic impairment, as midodrine undergoes enzymatic hydrolysis rather than hepatic metabolism 1
- Standard dosing can be used with appropriate monitoring 1
Elderly Patients
- No dose modification is necessary based on age alone, as pharmacokinetic studies show similar blood levels in patients ≥65 years versus younger patients 1
- However, monitor closely for supine hypertension and adverse effects 1
Pharmacokinetic Considerations
- The active metabolite desglymidodrine has a half-life of approximately 4 hours, supporting the three-times-daily dosing schedule 4
- Peak blood pressure effect occurs at 1 hour post-dose 3, 4
- Duration of action supports dosing intervals of 3-4 hours during waking hours 4
Monitoring and Safety
Blood Pressure Monitoring
- Monitor both supine and standing blood pressure regularly 1
- Discontinue if supine blood pressure increases excessively 1
- Supine hypertension occurs in up to 25% of patients but can be minimized by avoiding late-day dosing 5
Continuation Criteria
- Continue midodrine only in patients who demonstrate symptomatic improvement during initial treatment 1
- Assess improvement in standing systolic blood pressure and symptoms including dizziness, lightheadedness, syncope, weakness, and energy level 3, 2
Common Adverse Effects
- Most frequent: scalp pruritus/tingling (13.5% of patients), piloerection, and paresthesias 5, 3
- Supine hypertension (8%), urinary urgency/retention (4%), and chills 5, 3
- Overall adverse effects are mild to moderate, occurring in approximately 27% of treated patients versus 22% with placebo 3
Clinical Efficacy
- Midodrine significantly improves standing time, energy level, and reduces symptoms of dizziness, lightheadedness, syncope, weakness, fatigue, and depression compared to placebo 3, 2
- Efficacy is consistent across different etiologies of neurogenic orthostatic hypotension, including Shy-Drager syndrome, Bradbury-Eggleston syndrome, diabetic autonomic neuropathy, and Parkinson's disease 6