What is the use of Midodrine (ProAmatine)?

From the Guidelines

Midodrine is a recommended treatment for orthostatic hypotension, with a typical dosing regimen of 2.5-10 mg three times daily, as it has been shown to improve symptoms and increase standing blood pressure 1. The medication works by constricting blood vessels, which increases peripheral vascular resistance and raises blood pressure, counteracting the pooling of blood in the lower extremities that occurs when standing. Common side effects of midodrine include:

• Piloerection (goosebumps)
• Scalp tingling
• Urinary retention
• Supine hypertension It is essential to monitor blood pressure regularly while taking this medication, especially when lying down. Midodrine is contraindicated in patients with:
• Severe heart disease
• Acute kidney injury
• Urinary retention
• Pheochromocytoma
• Thyrotoxicosis It should not be used in patients with persistent or excessive supine hypertension. The most recent and highest quality study recommends midodrine as a first-line treatment for orthostatic hypotension, with a dose-dependent effect on standing blood pressure 1. Other treatments, such as fludrocortisone and droxidopa, may also be beneficial in patients with orthostatic hypotension, but midodrine is generally considered the first-line treatment due to its efficacy and safety profile 1. In patients with neurogenic orthostatic hypotension, midodrine has been shown to improve symptoms and increase standing blood pressure, with a typical dosing regimen of 2.5-10 mg three times daily 1. Overall, midodrine is a effective and safe treatment for orthostatic hypotension, and its use is recommended in patients with this condition, as long as they do not have any contraindications.

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, and has been shown to increase standing systolic blood pressure, improve standing time and energy level, and reduce clinical symptoms of orthostatic hypotension 3, 4

Efficacy of Midodrine

• Midodrine has been shown to be effective in increasing blood pressure and alleviating symptoms of orthostatic hypotension in several studies 3, 4, 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 3, 4
• A phase 4, double-blind, placebo-controlled, randomized, tilt-table study found that midodrine significantly increased the time to syncopal symptoms or near-syncope in patients with symptomatic orthostatic hypotension 5

Safety and Tolerability of Midodrine

• Midodrine is generally well-tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention, and chills 3, 4
• 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
• A study found that midodrine was safe and effective in patients with neurogenic orthostatic hypotension, with mild to moderate adverse events reported by 11.5% of patients 6

Combination Therapy with Midodrine

• A study found that single or combination treatment with midodrine and pyridostigmine was effective and safe in patients with orthostatic hypotension for up to 3 months 6
• Midodrine was found to be better than pyridostigmine at improving orthostatic hypotension-related symptoms, while combination therapy with both agents was found to be effective in improving orthostatic blood pressure drop 6