What is the highest recommended dose of midodrine (alpha-adrenergic agonist)?

Maximum Recommended Dose of Midodrine

The maximum recommended daily dose of midodrine is 30 mg, typically administered as 10 mg three times daily. 1

Dosing Guidelines

Midodrine is an alpha-adrenergic agonist with specific dosing requirements:

• Standard dosing: 10 mg, 3 times daily 1
• Timing: Doses should be given during daytime hours when the patient needs to be upright
• Interval: Approximately 4-hour intervals (can be given at 3-hour intervals if needed, but not more frequently)
• Suggested schedule: Morning (upon arising), midday, and late afternoon (not later than 6 PM) 1
• Maximum single dose: Single doses as high as 20 mg have been given but are associated with a high rate (about 45%) of severe and persistent systolic supine hypertension 1

Special Populations

• Renal impairment: Start with lower doses (2.5 mg) in patients with abnormal renal function since desglymidodrine (the active metabolite) is excreted renally 1
• Elderly patients: No dose modifications are 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 adjustments needed based on gender 1

Clinical Applications and Dosing

For Neurogenic Orthostatic Hypotension

• Studies have shown that 10 mg three times daily is effective for neurogenic orthostatic hypotension 2, 3
• Dose-response studies indicate a significant linear relationship between midodrine dosage and mean systolic blood pressure 2

For Hepatorenal Syndrome

• In hepatorenal syndrome, midodrine is typically used at 7.5-12.5 mg three times daily in combination with octreotide 4
• For treatment of HRS-AKI (hepatorenal syndrome-acute kidney injury), midodrine should be initiated at 7.5 mg and titrated upward to 12.5 mg three times daily with octreotide 4

For Hemodialysis Hypotension

• Mean treatment dose of 8 mg (range 2.5-25 mg) has been effective for hemodialysis hypotension 5

Important Precautions

• Supine hypertension: Monitor blood pressure regularly; discontinue if supine blood pressure increases excessively 1
• Timing restrictions: Do not give after evening meal or less than 4 hours before bedtime to reduce risk of supine hypertension during sleep 1
• Monitoring: Regular monitoring of supine and standing blood pressure is essential 1
• Ischemic side effects: When used for hepatorenal syndrome, be aware of potential ischemic side effects including angina and ischemia of fingers, skin, and intestine 4

Administration Strategy

1. Start with lower doses (2.5-5 mg three times daily)
2. Titrate upward based on symptomatic response and blood pressure measurements
3. Do not exceed 30 mg total daily dose
4. Continue only in patients who demonstrate symptomatic improvement during initial treatment

The pharmacokinetic profile of midodrine shows that the half-life of its active metabolite desglymidodrine is approximately 4 hours, supporting the three-times-daily dosing schedule 2.