What are the guidelines for using midodrine (prodrug of desglymidodrine) in patients with End-Stage Renal Disease (ESRD) and orthostatic hypotension?

Midodrine Use in End-Stage Renal Disease (ESRD)

Midodrine should be used cautiously in ESRD patients with orthostatic hypotension, with careful monitoring for adverse effects, as observational data suggests potential increased risks of cardiovascular events, hospitalization, and mortality despite short-term symptomatic benefits. 1

Efficacy in ESRD Patients

Midodrine has demonstrated effectiveness for intradialytic hypotension in ESRD patients:

• Meta-analysis shows midodrine improves nadir systolic blood pressure by an average of 13 mmHg (95% CI: 9-18 mmHg, P<0.0001) 1
• Studies report significant improvement in lowest intradialytic systolic blood pressure (from 96.6 to 114.7 mmHg) and diastolic blood pressure (from 53.2 to 59.0 mmHg) 2
• Reduces symptoms associated with intradialytic hypotension including cramps, fatigue, dizziness, and weakness 2
• Benefits appear to be maintained over extended periods (5-8 months) of follow-up 3

Dosing Recommendations

• For intradialytic hypotension:

  • Typical dose: 5-10 mg administered 30 minutes before hemodialysis session 2
  • Mean effective dose in studies: 5.5 mg (range 5-10 mg) 2

• For orthostatic hypotension:

  • Starting dose: 2.5 mg in patients with renal impairment 4
  • Typical maintenance dose: 5-20 mg three times daily 5
  • Last dose should be taken no later than 6 PM and at least 4 hours before bedtime to avoid supine hypertension 5

Mechanism and Pharmacokinetics

• Midodrine is a prodrug that forms the active metabolite desglymidodrine, an alpha-1 agonist 4
• Desglymidodrine acts on alpha-adrenergic receptors of arteriolar and venous vasculature, increasing vascular tone and elevating blood pressure 4
• Renal elimination of midodrine itself is insignificant, but renal clearance of desglymidodrine is approximately 385 mL/minute 4
• Midodrine is removed by dialysis 4

Monitoring Requirements

• Blood pressure should be monitored in both supine and standing positions before, during, and after dialysis 5, 4
• Assess renal function prior to initial use, though this is less relevant in ESRD patients 4
• Monitor for urinary retention, especially in patients with pre-existing urinary issues 5, 4
• Watch for bradycardia when used with cardiac glycosides, beta blockers, or other agents that reduce heart rate 4

Precautions and Contraindications

• Important safety concerns:

  • Observational data shows midodrine use in dialysis patients may be associated with higher risks of cardiovascular events, all-cause hospitalization, and mortality 1
  • Risk of supine hypertension (occurs in up to 25% of patients) 6
  • Use with caution in patients with urinary retention problems 4

• Drug interactions:

  • Use cautiously with other vasoconstrictors (phenylephrine, ephedrine, dihydroergotamine) 4
  • Avoid concomitant use with MAO inhibitors or linezolid 4
  • Alpha-adrenergic blocking agents can antagonize midodrine's effects 4
  • Monitor closely when used with cardiac glycosides, beta blockers, or salt-retaining steroids 4

Patient Education

• Instruct patients to avoid lying flat after taking midodrine
• Sleep with head of bed elevated to minimize supine hypertension
• Report symptoms of supine hypertension immediately (cardiac awareness, pounding in ears, headache, blurred vision)
• Discontinue medication if supine hypertension persists 4
• Be aware of common side effects: piloerection, scalp itching/tingling, urinary urgency, headache 5

Clinical Pitfalls to Avoid

• Do not use standard doses in ESRD patients - start with lower doses (2.5 mg) due to altered pharmacokinetics 4
• Do not administer the last daily dose close to bedtime - this increases risk of supine hypertension 5
• Do not use without monitoring for urinary retention - midodrine acts on alpha-adrenergic receptors of the bladder neck 4
• Do not overlook potential for serious adverse outcomes - despite symptomatic improvement, observational data suggests potential for increased cardiovascular events and mortality 1