What is the use of Midodrine (ProAmatine)?

From the Guidelines

Midodrine is recommended as a beneficial treatment for patients with syncope due to neurogenic orthostatic hypotension, with a typical dosing regimen starting at 2.5 mg three times daily, which can be increased to 5-10 mg three times daily as needed 1. The medication works by constricting blood vessels and increasing peripheral vascular resistance, which helps maintain blood pressure when changing positions.

• Common side effects include piloerection (goosebumps), scalp tingling, urinary retention, and supine hypertension.
• Patients should monitor their blood pressure regularly while taking this medication and should not lie down for at least 4 hours after each dose.
• Midodrine is contraindicated in patients with severe heart disease, acute kidney injury, urinary retention, pheochromocytoma, or thyrotoxicosis, and should be used cautiously in patients with kidney or liver impairment, with dose adjustments necessary in these populations 1. The use of midodrine may be limited by supine hypertension, and other common side effects, but it has been shown to improve symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension 1.
• The dose-dependent effect of midodrine usually corresponds to an increase in standing blood pressure.
• Midodrine is the only medication approved by the Food and Drug Administration for the treatment of symptomatic orthostatic hypotension 1. It is essential to weigh the potential risks of midodrine against its possible benefits, including the balance between increasing standing blood pressure and avoiding supine hypertension 1.
• Other treatments, such as fludrocortisone, droxidopa, and pyridostigmine, may also be beneficial in patients with syncope due to neurogenic orthostatic hypotension, but midodrine is a recommended first-line treatment 1.

From the FDA Drug Label

The potential for supine and sitting hypertension should be evaluated at the beginning of midodrine therapy. Supine hypertension can often be controlled by preventing the patient from becoming fully supine, i.e., sleeping with the head of the bed elevated. Patients should be told to avoid taking their dose if they are to be supine for any length of time, i. e., they should take their last daily dose of midodrine 3 to 4 hours before bedtime to minimize nighttime supine hypertension.

Midodrine use requires careful evaluation of the potential for supine hypertension. To minimize this risk, patients should be advised to:

• Sleep with the head of the bed elevated
• Avoid taking their dose if they are to be supine for any length of time
• Take their last daily dose of midodrine 3 to 4 hours before bedtime 2 2

From the Research

Midodrine Overview

• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration 3.
• It is used in the management of orthostatic hypotension, a condition characterized by a decrease in blood pressure upon standing, associated with symptoms such as dizziness, light-headedness, and syncope.

Efficacy of Midodrine

• Midodrine has been shown to significantly increase standing systolic blood pressure compared with placebo 3, 4.
• It improves standing time and energy level, and clinical symptoms of orthostatic hypotension, including dizziness, light-headedness, and syncope 3, 5.
• Comparative studies have shown midodrine to have similar efficacy to other agents, such as dihydroergotamine mesylate, norfenefrine, fludrocortisone, and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension 3, 6.

Safety and Tolerability

• Midodrine is well tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention, and chills 3, 6.
• The risk of supine hypertension, which is associated with midodrine therapy in up to 25% of patients, can be reduced by taking the final daily dose at least 4 hours before bedtime 3.
• Side effects are generally mild and can be controlled by reducing the dosage of midodrine 6, 5.

Dosage and Administration

• A 10-mg dose of midodrine prescribed two to three times daily is effective in increasing orthostatic blood pressure and ameliorating symptoms in patients with neurogenic orthostatic hypotension 4.
• The half-life of desglymidodrine, the active metabolite of midodrine, is approximately 4 hours 4.