Maximum Daily Dose of Midodrine
The maximum daily dose of midodrine is 30 mg per day, typically administered as 10 mg three times daily, with doses spaced approximately 4 hours apart during daytime hours when the patient is upright. 1
FDA-Approved Dosing Parameters
The standard therapeutic dose is 10 mg three times daily, which represents the typical maximum effective dose for most patients with orthostatic hypotension 1
Single doses up to 20 mg have been administered, but this higher single dose is associated with severe and persistent supine hypertension in approximately 45% of patients 1
Total daily doses exceeding 30 mg have been tolerated by some patients, but their safety and usefulness have not been systematically studied or established 1
Dosing Schedule and Timing Restrictions
Doses should be administered during daytime hours when upright activity is needed, with a suggested schedule of: upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
The final dose must be taken at least 4 hours before bedtime and should not be given after the evening meal to reduce the risk of supine hypertension during sleep 1, 2
Doses may be given at 3-hour intervals if required to control symptoms, but not more frequently than this 1
Dose Titration Strategy
Initial dosing should start at 2.5-5 mg three times daily, then titrate upward based on standing blood pressure measured 1 hour post-dose (when peak effect occurs) and symptom improvement 3, 4
The duration of action is 2-4 hours, with a half-life of the active metabolite (desglymidodrine) of approximately 4 hours 3, 4
Gradual titration to the standard 10 mg three times daily dose is recommended, as this dose significantly increases standing systolic blood pressure by approximately 22 mm Hg (28% increase) and improves orthostatic symptoms 5
Special Population Adjustments
Patients with renal impairment should initiate treatment cautiously at 2.5 mg doses, as the active metabolite desglymidodrine is renally excreted 1
For hepatorenal syndrome, higher initial dosing of 7.5 mg three times daily, titrated to 12.5 mg three times daily (total 37.5 mg/day), has been used in combination with octreotide, though this exceeds the standard orthostatic hypotension maximum 6, 3
Hemodialysis patients may use 5-10 mg administered 30 minutes before dialysis, as midodrine is removed by dialysis 3
Critical Safety Considerations
Supine hypertension is the dose-limiting adverse effect, occurring in up to 25% of patients, and can be mitigated by avoiding late-day dosing and elevating the head of the bed 2, 5
Treatment should be discontinued if supine blood pressure increases excessively or if patients do not achieve symptomatic improvement during initial treatment 1
Monitor for reflex bradycardia, particularly in patients taking beta-blockers, digoxin, or non-dihydropyridine calcium channel blockers 3
Other common adverse effects include piloerection (13.5%), pruritus, paresthesias, urinary retention/urgency (4%), and chills 2, 5