What is the recommended dosing frequency of Midodrine for a patient with orthostatic hypotension taking Metoprolol Succinate ER (Metoprolol) and Sacubitril-Valsartan?

Midodrine Dosing for Orthostatic Hypotension in a Patient with Heart Failure

Midodrine should be dosed three times daily (10 mg TID) rather than once daily for this patient with orthostatic hypotension, with the last dose given no later than 6 PM to avoid supine hypertension during sleep. 1

Recommended Dosing Schedule

• Standard dosing: 10 mg three times daily at approximately 4-hour intervals 1
• Timing: Morning (upon arising), midday, and late afternoon (not later than 6 PM) 1
• Maximum daily dose: 30 mg total daily dose 1
• Important: Do not give after evening meal or less than 4 hours before bedtime 1

Rationale for Three-Times-Daily Dosing

1. FDA-approved dosing: The FDA label specifically recommends TID dosing to maintain adequate blood pressure throughout daytime hours when the patient needs to be upright 1

2. Guideline recommendation: The 2023 ACC Expert Consensus recommends midodrine at 2.5 mg three times daily, titrated up to 10 mg three times daily for orthostatic hypotension 2

3. Pharmacokinetics: Midodrine is a prodrug that undergoes enzymatic hydrolysis to its active metabolite (desglymidodrine), requiring multiple daily doses to maintain therapeutic effect throughout the day 3

4. Clinical evidence: Multiple clinical trials have demonstrated efficacy with TID dosing, showing significant improvement in standing blood pressure and orthostatic symptoms 4, 5

Special Considerations with Current Medications

• Metoprolol and Sacubitril-Valsartan: Both medications can potentially lower blood pressure, making adequate treatment of orthostatic hypotension important

• Heart failure considerations: The ACC Expert Consensus notes that midodrine "may be poorly tolerated in HF" 2, so careful monitoring is needed given the patient's Sacubitril-Valsartan and Metoprolol (indicating heart failure)

• Apixaban (Eliquis): No significant interactions with midodrine, but monitoring for symptoms of orthostasis remains important as falls could increase bleeding risk

Monitoring Recommendations

• Blood pressure monitoring: Regularly check both supine and standing blood pressure to assess efficacy and monitor for supine hypertension 6

• Timing of monitoring: Measure BP after 5 minutes of lying or sitting, then 1 and 3 minutes after standing 6

• Symptom assessment: Document improvement in symptoms such as dizziness, lightheadedness, and syncope 6

Potential Adverse Effects to Watch For

• Supine hypertension: Occurs in up to 25% of patients on midodrine 3
• Urinary retention: Monitor especially with concomitant use of other medications
• Piloerection (goosebumps) and pruritus (itching)
• Paresthesias (tingling sensations)
• Nightmares: A rare but reported side effect, especially if taken too late in the day 7

Important Cautions

• Timing of last dose: The last dose should be taken no later than 6 PM to minimize the risk of supine hypertension during sleep 1

• Dosage adjustment: If the patient develops supine hypertension, consider reducing the dose or discontinuing the medication 1

• Efficacy assessment: Continue midodrine only if symptomatic improvement is demonstrated 1

• Renal function: Since the patient is on multiple medications that can affect renal function, monitor kidney function as desglymidodrine is excreted renally 1

Once-daily dosing would be insufficient to maintain adequate blood pressure throughout the day for a patient with orthostatic hypotension and would not align with established guidelines or the FDA-approved dosing regimen.