What is the frequency of administration for midodrine (ProAmatine) in treating orthostatic hypotension?

From the Guidelines

Midodrine is typically given three times daily, with doses spaced approximately 3-4 hours apart during daytime hours, as recommended by the most recent guidelines 1. The standard dosing schedule is 10 mg three times daily, usually administered at approximately 8 AM, noon, and 4 PM. The last dose should be taken at least 3-4 hours before bedtime to avoid supine hypertension while sleeping, as cautioned in the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1. Treatment often begins with a lower dose of 2.5 mg three times daily, which can be gradually increased to 10 mg three times daily based on patient response and tolerance. The maximum recommended daily dose is 30 mg (10 mg three times daily). Midodrine works by stimulating alpha-1 adrenergic receptors, causing constriction of both arterial and venous blood vessels, which increases blood pressure, as explained in the study on cardiovascular autonomic neuropathy in diabetes 1. This makes it effective for treating orthostatic hypotension, but also explains why the timing of doses is important to prevent dangerous blood pressure elevations when the patient is lying down. Some key points to consider when prescribing midodrine include:

• Monitoring for supine hypertension, as warned in the 2018 standards of medical care in diabetes 1
• Adjusting the dose based on patient response and tolerance
• Avoiding the use of midodrine in patients with certain medical conditions, such as supine hypertension or pheochromocytoma
• Encouraging patients to drink plenty of fluids and eat a balanced diet to help manage orthostatic hypotension, as suggested in the 2021 standards of medical care in diabetes 1.

From the FDA Drug Label

Midodrine has been studied in 3 principal controlled trials, one of 3-weeks duration and 2 of 1 to 2 days duration. All studies were randomized, double-blind and parallel-design trials in patients with orthostatic hypotension of any etiology and supine-to-standing fall of systolic blood pressure of at least 15 mmHg accompanied by at least moderate dizziness/lightheadedness Patients with pre-existing sustained supine hypertension above 180/110 mmHg were routinely excluded. In a 3-week study in 170 patients, most previously untreated with midodrine, the midodrine-treated patients (10 mg t.i.d., with the last dose not later than 6 P.M.) had significantly higher (by about 20 mmHg) 1-minute standing systolic pressure 1 hour after dosing (blood pressures were not measured at other times) for all 3 weeks In a 2-day study, after open-label midodrine, known midodrine responders received midodrine 10 mg or placebo at 0,3 and 6 hours.

The recommended dosing frequency of midodrine is three times a day (t.i.d.), with the last dose not later than 6 P.M. 2

• The dose can be given at 0,3, and 6 hours in known responders.
• 10 mg is the dose used in the studies. The dosing frequency may vary based on patient response and tolerability.

From the Research

Administration Frequency of Midodrine

• The frequency of midodrine administration is not explicitly stated in the provided studies, but its usage is discussed in the context of managing orthostatic hypotension.
• According to 3, the risk of supine hypertension associated with midodrine therapy can be reduced by taking the final daily dose at least 4 hours before bedtime, implying a daily administration schedule.
• 4 discusses the efficacy and safety of midodrine in patients with refractory orthostatic hypotension but does not specify the administration frequency.
• Other studies, such as 5, 6, and 7, focus on different aspects of orthostatic hypotension management, including the use of fludrocortisone, the treatment of primary orthostatic hypotension, and the comparison of droxidopa and midodrine, but do not provide information on the administration frequency of midodrine.

Dosage and Administration Considerations

• The studies suggest that midodrine is effective in managing orthostatic hypotension, but the optimal dosage and administration schedule may vary depending on individual patient needs and responses.
• 3 and 4 highlight the importance of considering the risk of supine hypertension and adjusting the dosage or administration schedule accordingly.
• However, the specific details on how often midodrine can be given are not provided in the available evidence, indicating a need for further research or consultation of clinical guidelines for personalized treatment recommendations.