What is the dose of midodrine (ProAmatine) for orthostatic hypotension?

From the Guidelines

Midodrine should be started at a dose of 2.5 mg 3 times daily, with the option to titrate upward as needed to a maximum of 10 mg 3 times daily, based on the most recent and highest quality evidence from the 2023 study 1. The dosing regimen should be individualized, with the goal of minimizing postural symptoms rather than restoring normotension. Key considerations in the management of orthostatic hypotension with midodrine include:

• Initiating treatment with a low dose and gradually increasing as needed and tolerated
• Avoiding supine hypertension by not taking the last dose too close to bedtime
• Monitoring for potential side effects such as piloerection, scalp tingling, urinary retention, and bradycardia
• Adjusting the dose based on standing blood pressure measurements and symptom improvement
• Considering reduced dosing in patients with renal impairment
• Advising patients to avoid lying flat for 4 hours after taking midodrine and to regularly monitor their blood pressure in both sitting and standing positions. While other studies, such as those from 2011 1 and 2022 1, provide additional guidance on the management of orthostatic hypotension, the 2023 study 1 provides the most recent and highest quality evidence to inform clinical practice.

From the FDA Drug Label

The recommended dose of midodrine hydrochloride tablets is 10 mg, 3 times daily. Doses may be given in 3-hour intervals, if required, to control symptoms, but not more frequently. 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 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 Although this has not been systematically studied, it is recommended that treatment of these patients be initiated using 2.5 mg doses in patients with abnormal renal function.

The recommended dose of midodrine is 10 mg, 3 times daily.

• The maximum single dose is 20 mg, but it is associated with a high risk of supine hypertension.
• The maximum daily dose is not established, but doses greater than 30 mg have been tolerated by some patients.
• In patients with abnormal renal function, the recommended initial dose is 2.5 mg 2.

From the Research

Dose of Midodrine

• The dose of midodrine varies depending on the patient's condition and response to treatment.
• A study published in 1998 found that 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 3.
• Another study published in 1998 reviewed the therapeutic use of midodrine in the management of orthostatic hypotension and found that the drug is well tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention, and chills 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 4.
• A phase 4, double-blind, placebo-controlled, randomized, tilt-table study published in 2016 found that midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension, with a significant increase in time to syncopal symptoms or near-syncope compared to placebo 5.

Dosage Recommendations

• The recommended dose of midodrine is 2.5-10 mg, taken two to three times daily 3.
• The dose may need to be adjusted based on the patient's response to treatment and the presence of any adverse events.
• It is essential to monitor the patient's blood pressure and adjust the dose accordingly to minimize the risk of supine hypertension 4.

Comparison with Other Treatments

• Midodrine has been compared to other treatments for orthostatic hypotension, including fludrocortisone, and has been found to be effective in increasing orthostatic blood pressure and ameliorating symptoms 4, 6.
• A Cochrane review published in 2021 found that fludrocortisone is a first- or second-line pharmacological therapy for orthostatic hypotension, but the evidence for its effectiveness is limited, and more research is needed to fully understand its benefits and harms 7.