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

From the Guidelines

Midodrine should be started at a dose of 2.5 mg three times daily, with the option to titrate up to 10 mg three times daily based on symptoms and blood pressure response, as recommended by the most recent guidelines 1. The dosing of midodrine is crucial in managing orthostatic hypotension, and the goal is to minimize postural symptoms rather than restore normotension.

• The initial dose of 2.5 mg three times daily can be adjusted based on the patient's response and tolerability.
• The maximum dose of 10 mg three times daily should not be exceeded, and patients should be monitored for supine hypertension.
• Midodrine works by activating alpha-1 adrenergic receptors, causing arterial and venous constriction, which increases blood pressure, but also carries the risk of supine hypertension.
• Patients should be advised to avoid lying flat for 4 hours after taking each dose and to monitor for symptoms like headache, pounding in ears, or blurred vision that might indicate elevated blood pressure, as noted in the study 1. Key considerations in the use of midodrine include:
• Monitoring for supine hypertension, particularly in patients with cardiac or renal disease.
• Adjusting the dose based on the patient's response and tolerability.
• Avoiding the use of midodrine in patients with certain medical conditions, such as heart failure, as noted in the study 1. The study 1 provides additional context for the use of midodrine in the treatment of orthostatic hypotension, but the most recent guidelines 1 provide the recommended dosing regimen.

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 study and the condition being treated.
• 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 found that midodrine significantly increased standing systolic blood pressure, with the increase peaking at 1 hour, and that there was a significant linear relation between midodrine dosage and mean systolic blood pressure 3.
• A study published in 1989 found that midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine, and that the most commonly experienced adverse effects are generally mild and can be controlled by reducing the dosage of midodrine 4.
• A study published in 1993 found that midodrine is an effective and safe agent for the treatment of neurogenic orthostatic hypotension, and that symptoms such as fainting, blurred vision, and depressed feelings were significantly improved even at lower doses (p < 0.05 or less) 5.
• The optimal dose of midodrine for orthostatic hypotension is not established, but studies suggest that doses ranging from 2.5 to 10 mg three times daily may be effective 3, 5.

Adverse Effects

• The most commonly reported adverse events associated with midodrine therapy are piloerection, pruritus, paraesthesias, urinary retention, and chills 6.
• 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 6.
• Midodrine is generally well tolerated, and the adverse effects are usually mild and can be controlled by reducing the dosage 4.

Comparison with Other Treatments

• Midodrine has been compared to other treatments for orthostatic hypotension, including fludrocortisone, and has been found to be effective and safe 6, 7.
• A study published in 2021 found that fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension, but that the evidence for its effectiveness is very uncertain 7.