What are the common dosing parameters for midodrine (ProAmatine) in treating orthostatic hypotension?

Midodrine Dosing Parameters for Orthostatic Hypotension

The recommended dosing for midodrine (ProAmatine) in treating 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

Dosing Schedule and Administration

• Initial dosing should begin with 10 mg three times daily, with doses spaced approximately 4 hours apart during daytime hours 1
• The last dose should be taken at least 4 hours before bedtime to minimize the risk of supine hypertension 2, 3
• Midodrine forms an active metabolite, desglymidodrine, which is an alpha1-agonist that increases vascular tone and elevates blood pressure 2
• The therapeutic effect peaks 1-2 hours after administration and can persist for 2-3 hours, with standing systolic blood pressure typically elevated by 15-30 mmHg 2

Clinical Efficacy and Monitoring

• Midodrine is the only medication FDA-approved specifically for the treatment of symptomatic orthostatic hypotension 1
• The therapeutic goal is to minimize postural symptoms rather than to restore normotension 1, 4
• After initiation of treatment, midodrine should be continued only in patients who report significant symptomatic improvement 2
• Regular monitoring of supine and standing blood pressure is essential to assess efficacy and detect potential supine hypertension 4

Side Effects and Precautions

• Common side effects include piloerection (goosebumps), pruritus (itching), paresthesias, urinary retention, and chills 2, 3
• Supine hypertension occurs in up to 25% of patients and can be minimized by taking the final daily dose at least 4 hours before bedtime 3
• Midodrine should be used cautiously in patients with congestive heart failure and in those using other negative chronotropic agents such as beta-blockers, digoxin, and non-dihydropyridine calcium channel blockers 5
• Concomitant use with other alpha-adrenergic agents should be avoided as this may aggravate supine hypertension 5
• Midodrine can antagonize the actions of alpha-adrenergic blockers (such as terazosin, prazosin, and doxazosin) and could result in urinary retention 5

Special Populations

• In hemodialysis patients, midodrine is effectively cleared by hemodialysis with its half-life reduced to 1.4 hours 5
• For dialysis patients, a single dose of 5 mg administered 30 minutes before dialysis has been shown to improve intradialytic and postdialytic blood pressure 5
• Midodrine has minimal cardiac and central nervous system effects due to its specificity for peripheral alpha-receptors and poor penetration across the blood-brain barrier 5, 2

Treatment Approach

• Non-pharmacological measures should be tried first or used concurrently with midodrine, including increased fluid and salt intake, physical counter-maneuvers, and compression garments 1, 4
• For patients with resistant orthostatic hypotension, combination approaches may be necessary, such as midodrine with other modalities 5
• Midodrine should be used only in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacological treatment 2