What are the current guidelines for midodrine (ProAmatine) withhold parameters?

Guidelines for Midodrine Withhold Parameters

Midodrine should be withheld if the patient develops supine systolic hypertension or bradycardia, as these are the primary safety concerns requiring cessation of therapy. 1

Monitoring Parameters and Withhold Criteria

Blood Pressure Parameters

• Withhold midodrine if supine systolic hypertension develops (occurs in <10% of patients on long-term therapy) 1
• Monitor blood pressure in both supine and standing positions to assess efficacy and detect supine hypertension 1
• Particular caution is needed in patients with cardiac amyloidosis, where severe orthostatic hypotension requiring midodrine may be a contraindication to heart transplantation 1

Cardiovascular Parameters

• Monitor for bradycardia as midodrine is associated with reflex parasympathetic stimulation 1
• Use with caution in patients with congestive heart failure (CHF) as it may be poorly tolerated 1
• Avoid concomitant use with other negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) due to increased risk of bradycardia 1

Drug Interactions Requiring Caution or Withholding

• Withhold or avoid concomitant use with other α-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) as this may aggravate supine hypertension 1
• Use caution with α-adrenergic blockers (terazosin, prazosin, doxazosin) as midodrine may antagonize their effects and potentially cause urinary retention 1

Timing Considerations

• Final daily dose should be taken at least 4 hours before bedtime to reduce the risk of supine hypertension 2
• For hemodialysis patients, administer 30 minutes before dialysis session to prevent intradialytic hypotension 1

Special Populations

Dialysis Patients

• Midodrine is effectively cleared by hemodialysis with half-life reduced to 1.4 hours 1
• Risk of developing supine hypertension is possible but rare in dialysis patients since both prodrug and active metabolite are removed effectively 1
• Standard dose for dialysis patients is 5 mg administered 30 minutes before dialysis session 1

Cardiac Amyloidosis Patients

• Standard dosing is 2.5 mg three times daily, titrated to symptoms and blood pressure, with maximum dose of 10 mg three times daily 1
• May be poorly tolerated in heart failure patients 1

Common Side Effects Requiring Monitoring

• Piloerection, scalp itching or tingling 1, 2
• Nausea and heartburn 1
• Urinary urgency or retention 1, 2
• Headache, nervousness, and sleep disturbance 1
• Chills and paresthesias 2

Algorithm for Midodrine Management

1. Initial assessment: Verify appropriate indication (orthostatic hypotension, intradialytic hypotension) 1
2. Dosing: Start with 2.5-5 mg three times daily, with maximum dose of 10 mg three times daily 1
3. Timing: Administer doses during daytime hours with the last dose at least 4 hours before bedtime 2
4. Regular monitoring:
   • Check supine and standing blood pressure 1
   • Monitor for bradycardia 1
   • Assess for urinary retention 1
5. Withhold parameters:
   • Development of supine systolic hypertension 1
   • Significant bradycardia 1
   • Severe urinary retention 1

Pitfalls and Caveats

• Midodrine is not a cure for orthostatic hypotension but rather a symptomatic treatment 1
• Long-term use requires ongoing monitoring for supine hypertension 1
• In dialysis patients, the combination of cool dialysate and predialysis doses of midodrine may lead to decreased frequency and intensity of symptoms of intradialytic hypotension without side effects 1
• Efficacy should be assessed by improvement in orthostatic symptoms (dizziness, lightheadedness, weakness, fatigue, syncope) and standing blood pressure 3