What are the considerations for using midodrine (a medication for orthostatic hypotension) in patients with End-Stage Renal Disease (ESRD) and cirrhosis?

Midodrine Use in Patients with ESRD and Cirrhosis

Midodrine can be used cautiously in patients with ESRD and cirrhosis, primarily for refractory ascites on a case-by-case basis, with careful monitoring for adverse effects and contraindications. 1

Indications in ESRD and Cirrhosis

ESRD Considerations

• Midodrine is effective for intradialytic hypotension in ESRD patients
• Typical dosing: 5-10 mg administered 30 minutes before hemodialysis 2
• Benefits include:
  • Significant improvement in lowest intradialytic systolic and diastolic blood pressure
  • Reduction in symptoms such as cramps, fatigue, dizziness, and weakness
  • Improved post-hemodialysis blood pressure

Cirrhosis Considerations

• Midodrine may be appropriate for refractory ascites in cirrhosis 1
• Can be used in combination with octreotide for hepatorenal syndrome (HRS) when terlipressin is unavailable 1
• Starting dose for refractory ascites: 7.5 mg three times daily 3
• For HRS: 7.5 mg three times daily, which can be increased to 12.5 mg three times daily 3

Dosing Adjustments and Precautions

Renal Impairment

• Lower starting dose of 2.5 mg recommended in renal impairment 4
• Renal function should be assessed prior to initiating therapy 4
• Desglymidodrine (active metabolite) is eliminated via the kidneys, leading to potentially higher blood levels in renal impairment 4

Hepatic Impairment

• Use with caution in hepatic impairment as the liver plays a role in midodrine metabolism 4
• Midodrine should not be used in patients with acute kidney injury with serum creatinine ≥5 mg/dL 3

Administration Guidelines

• Administer at approximately 4-hour intervals during daytime only 3
• Last dose should be taken no later than 6 PM and at least 4 hours before bedtime to avoid supine hypertension 4
• For ESRD patients on dialysis, administer 30 minutes before hemodialysis session 2
• Midodrine is removed by dialysis 4

Monitoring Requirements

• Regular blood pressure monitoring in both supine and standing positions 3
• Monitor for supine hypertension (occurs in up to 25% of patients) 5
• Patients should sleep with head of bed elevated (10°) 3
• Monitor for urinary retention, especially in patients with pre-existing urinary issues 4

Adverse Effects to Watch For

1. Cardiovascular:

   • Supine hypertension (most serious concern)
   • Bradycardia (due to vagal reflex)

2. Urologic:

   • Urinary urgency or retention (due to alpha-adrenergic effects on bladder neck)

3. Other common side effects:

   • Piloerection (goosebumps)
   • Scalp itching or tingling
   • Paresthesias
   • Nausea and heartburn

Drug Interactions Relevant to ESRD and Cirrhosis

• Use caution with concomitant medications that increase blood pressure (e.g., vasoconstrictors) 4
• Avoid MAO inhibitors or linezolid with midodrine 4
• Monitor closely when used with:
  • Cardiac glycosides (may enhance bradycardia)
  • Beta blockers (may reduce heart rate further)
  • Alpha-adrenergic blocking agents (can antagonize midodrine effects)
  • Salt-retaining steroids like fludrocortisone (increased risk of supine hypertension)

Clinical Pearls

• Midodrine is a prodrug that forms the active metabolite desglymidodrine 4
• Peak blood concentrations of the active metabolite occur 1-2 hours after dosing 4
• Half-life of desglymidodrine is approximately 3-4 hours 4
• Food does not affect the bioavailability of desglymidodrine 4
• Patients should be instructed to avoid taking their dose if they will be supine for any length of time 4

By carefully considering these factors and implementing appropriate monitoring, midodrine can be safely used in patients with ESRD and cirrhosis to manage orthostatic hypotension, intradialytic hypotension, and as an adjunct therapy for refractory ascites.