What is the maximum recommended dosage of midodrine (alpha-1 adrenergic receptor agonist)?

Maximum Dosage of Midodrine

The maximum recommended dosage of midodrine is 30 mg per day, administered as 10 mg three times daily. 1

Dosing Guidelines

Midodrine dosing should follow these specific parameters:

• Starting dose: 10 mg, 3 times daily 1
• Maximum single dose: 10 mg (though single doses as high as 20 mg have been given to patients, they cause severe and persistent systolic supine hypertension in about 45% of patients) 1
• Maximum daily dose: 30 mg total 1
• Dosing interval: Approximately 4-hour intervals; can be given at 3-hour intervals if needed to control symptoms, but not more frequently 1
• Timing of doses: During daytime hours when the patient needs to be upright (suggested schedule: morning upon arising, midday, and late afternoon - not later than 6 PM) 1

Important Administration Considerations

1. Avoid evening dosing: Do not administer after the evening meal or less than 4 hours before bedtime to reduce the risk of supine hypertension during sleep 1

2. Blood pressure monitoring: Regular monitoring of supine and standing blood pressure is essential; discontinue if supine blood pressure increases excessively 1

3. Special populations:

   • Renal impairment: Initiate at lower doses (2.5 mg) in patients with abnormal renal function since desglymidodrine (active metabolite) is excreted renally 1
   • Elderly: No dose modifications necessary as blood levels are similar in patients ≥65 years compared to younger patients 1

Clinical Applications and Dosing in Specific Conditions

Orthostatic Hypotension

• Standard dosing applies (10 mg three times daily) 1
• Clinical studies have demonstrated that the 10 mg dose significantly increases standing systolic blood pressure and improves symptoms compared to placebo 2, 3

Hepatorenal Syndrome (HRS)

• For HRS-AKI: Midodrine should be initiated at 7.5 mg and titrated upward to 12.5 mg three times daily, used in combination with octreotide 4
• This combination is used when terlipressin is not available but is considered inferior to terlipressin for HRS treatment 4

Pharmacokinetic Considerations

• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the active metabolite desglymidodrine 5
• The half-life of desglymidodrine is approximately 4 hours, which supports the recommended dosing interval 2
• Peak effect on blood pressure occurs approximately 1 hour after administration 2

Monitoring and Safety

• Common side effects: Piloerection, pruritus, paresthesias, urinary retention, and chills 5
• Supine hypertension: Occurs in up to 25% of patients; risk can be reduced by taking the final daily dose at least 4 hours before bedtime 5
• Blood pressure goals: When treating HRS, the goal is to increase mean arterial pressure by ≥10 mmHg 4

While some patients have tolerated total daily doses greater than 30 mg, the safety and usefulness of these higher doses have not been systematically studied or established 1.