What is the maximum recommended dose of midodrine (proamatine)?

Maximum Recommended Dose of Midodrine

The maximum recommended dose of midodrine is 30 mg per day, typically given as 10 mg three times daily, with doses not administered later than 6 PM to avoid supine hypertension during sleep. 1

Dosing Guidelines

Standard Dosing

• Starting dose: 10 mg three times daily 1
• Timing: Doses should be given during daytime hours when the patient needs to be upright
• Recommended schedule: Upon arising in the morning, midday, and late afternoon (not later than 6 PM) 1
• Interval: Typically 4-hour intervals, but can be given at 3-hour intervals if needed to control symptoms 1

Dose Adjustments

• Single doses as high as 20 mg have been given to patients, but this higher dose is associated with a high rate (approximately 45%) of severe and persistent systolic supine hypertension 1
• Total daily doses greater than 30 mg have been tolerated by some patients, but their safety and usefulness have not been systematically established 1

Special Populations

• Renal impairment: Start with 2.5 mg doses in patients with abnormal renal function 1
• Elderly patients: No dose modifications necessary based on age, as blood levels of midodrine and desglymidodrine were similar when comparing patients 65 or older vs. younger than 65 1
• Gender: No dose modifications necessary based on gender 1

Clinical Applications

Orthostatic Hypotension

• For neurogenic orthostatic hypotension, midodrine can be dosed at 5-20 mg three times daily 2
• A double-blind study 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

Hepatorenal Syndrome

• For hepatorenal syndrome, midodrine should be initiated at doses of 7.5 mg and titrated upward to 12.5 mg 3 times daily, used in combination with octreotide 4
• In patients with acute-on-chronic liver failure, midodrine has been shown to improve hemodynamics, tolerability of diuretics, and ascites control 5

Monitoring and Safety Considerations

Blood Pressure Monitoring

• Supine and standing blood pressure should be monitored regularly 1
• Administration should be stopped if supine blood pressure increases excessively 1

Timing Considerations

• Midodrine should not be given after the evening meal or less than 4 hours before bedtime to reduce the risk of supine hypertension during sleep 1
• Treatment should be continued only in patients who attain symptomatic improvement during initial treatment 1

Side Effects

• Main adverse effects include pilomotor reactions, urinary retention, and supine hypertension 6
• In hemodialysis patients, mild side effects such as flush sensation, neck soreness, and headache have been reported 7

Efficacy

• Midodrine significantly increases standing systolic blood pressure, with the increase peaking at 1 hour after administration 3
• There is a significant linear relationship between midodrine dosage and mean systolic blood pressure 3
• The half-life of desglymidodrine (the active metabolite) is approximately 4 hours, which supports the recommended dosing interval 3

By adhering to the maximum daily dose of 30 mg and following the recommended administration schedule, patients can maximize the benefits of midodrine while minimizing the risk of adverse effects, particularly supine hypertension.