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 blood pressure by stimulating alpha-1 receptors on vascular smooth muscle. Some key points to consider when prescribing midodrine include:

• Doses should be taken during waking hours (morning, midday, and late afternoon, but not after 6 PM) to avoid supine hypertension while sleeping
• Blood pressure monitoring is essential when starting this medication, and patients should avoid taking it when lying down
• Midodrine is contraindicated in patients with severe heart disease, acute kidney injury, urinary retention, pheochromocytoma, or thyrotoxicosis
• Common side effects include piloerection (goosebumps), scalp tingling, urinary retention, and supine hypertension
• The medication typically takes effect within an hour and lasts for 2-3 hours, making the timing of doses important for symptom management throughout the day Other treatments for orthostatic hypotension may include:
• Fludrocortisone, which stimulates renal sodium retention and expands fluid volume 1
• Physical counter-pressure maneuvers, such as leg crossing and squatting, which can increase blood pressure and improve orthostatic tolerance 1
• Compression garments, which can improve orthostatic symptoms and blunt associated decreases in blood pressure 1
• Increased salt and fluid intake, which may improve blood pressure and decrease symptoms from orthostatic hypotension, although the long-term effects of these treatments are unknown 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 an extended period
• Take their last daily dose 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, significantly increasing 1-minute standing systolic blood pressure compared with placebo 3.

Efficacy and Safety

• Midodrine has been shown to be effective in increasing orthostatic blood pressure and ameliorating symptoms in patients with neurogenic orthostatic hypotension 4, 5.
• The drug is well tolerated, with common adverse events including piloerection, pruritus, paraesthesias, urinary retention, and chills 3.
• However, midodrine can cause supine hypertension in up to 25% of patients, which can be reduced by taking the final daily dose at least 4 hours before bedtime 3.
• A novel side effect of midodrine-induced nightmares has been reported, highlighting the importance of careful consideration when prescribing midodrine in older people with orthostatic hypotension 6.

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.

Comparison with Other Treatments

• Midodrine has been shown to have similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone, and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension 3.
• Midodrine and droxidopa possess the most evidence with respect to increasing blood pressure and alleviating symptoms in primary orthostatic hypotension 7.