What is the highest recommended dose of midodrine (alpha-1 adrenergic receptor agonist) for treating orthostatic hypotension?

From the Guidelines

The highest recommended dose of midodrine for treating orthostatic hypotension is 10 mg taken three times daily, for a maximum daily dose of 30 mg. This recommendation is based on the most recent and highest quality study available, which is the 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis 1. Midodrine should be administered during daytime hours when the patient needs to be upright, typically with doses taken upon waking, at midday, and in the late afternoon (no later than 6 PM). The medication should not be taken within 4 hours of bedtime to avoid supine hypertension. Treatment typically begins with a lower dose of 2.5 mg three times daily, which can be gradually increased to the maximum dose based on symptomatic response and blood pressure measurements. Midodrine works by activating alpha-1 adrenergic receptors, causing arterial and venous vasoconstriction, which increases peripheral vascular resistance and raises blood pressure. This helps counteract the drop in blood pressure that occurs when standing in patients with orthostatic hypotension. Patients should monitor their blood pressure regularly while taking midodrine and report any signs of supine hypertension, such as severe headache or pounding in the ears when lying down.

Some key points to consider when prescribing midodrine include:

• The dosing should be individually tailored, with the first dose taken before arising and use avoided several hours before planned recumbency, particularly in patients with documented supine hypertension 1.
• Adverse events associated with midodrine include pilomotor reactions, pruritus, supine hypertension, bradycardia, gastrointestinal symptoms, and urinary retention 1.
• Midodrine is the only medication approved by the Food and Drug Administration for the treatment of symptomatic orthostatic hypotension 1.

It's also important to note that other treatments, such as physical counter-pressure maneuvers, compression garments, and other medications like droxidopa and fludrocortisone, may be beneficial in patients with orthostatic hypotension, and should be considered as part of a comprehensive treatment plan 1. However, the highest recommended dose of midodrine remains 10 mg taken three times daily, for a maximum daily dose of 30 mg.

From the FDA Drug Label

The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily... Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established... Single doses as high as 20 mg have been given to patients, but severe and persistent systolic supine hypertension occurs at a high rate (about 45%) at this dose

• The highest recommended dose of midodrine for treating orthostatic hypotension is not explicitly stated, but single doses as high as 20 mg have been given to patients.
• However, due to the risk of severe and persistent systolic supine hypertension, doses above 10 mg should be used with caution.
• Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been studied systematically or established 2.

From the Research

Highest Recommended Dose of Midodrine

The highest recommended dose of midodrine for treating orthostatic hypotension is not explicitly stated as a single maximum dose across all studies, but rather as a range of effective doses.

• The studies suggest that midodrine is effective in improving blood pressure and ameliorating symptoms of orthostatic hypotension at doses ranging from 2.5 mg to 10 mg, taken three times a day 3, 4, 5, 6.
• A dose of 10 mg three times a day is commonly cited as effective in increasing orthostatic blood pressure and ameliorating symptoms in patients with neurogenic orthostatic hypotension 3, 4, 5, 6.
• One study found a significant linear relation between midodrine dosage and mean systolic blood pressure, with the 10 mg and 20 mg doses showing significant increases in standing systolic blood pressure 4.
• However, the 20 mg dose is not consistently recommended across studies, and the majority of evidence supports the use of 10 mg three times a day as the standard effective dose 3, 4, 5, 6, 7.

Adverse Effects and Safety

• The main adverse effects of midodrine include pilomotor reactions, urinary retention, and supine hypertension 3.
• Other reported side effects include scalp pruritus/tingling, supine hypertension, and feelings of urinary urgency 6.
• Midodrine is generally considered safe and well-tolerated, with most side effects being mild to moderate in severity 3, 6, 7.