What are the contraindications of midodrine?

Contraindications of Midodrine

Midodrine is absolutely contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma, thyrotoxicosis, and persistent/excessive supine hypertension. 1

Absolute Contraindications (FDA-Labeled)

The FDA drug label explicitly lists the following as absolute contraindications 1:

• Severe organic heart disease 1
• Acute renal disease 1
• Urinary retention 1
• Pheochromocytoma 1
• Thyrotoxicosis 1
• Persistent and excessive supine hypertension 1

Relative Contraindications and High-Risk Populations

Heart Failure Patients

Midodrine should be used with extreme caution or avoided entirely in heart failure patients, as it may be poorly tolerated and potentially harmful. 2

• The American College of Cardiology specifically warns that midodrine may be poorly tolerated in heart failure patients due to increased afterload from vasoconstriction 2
• Recent 2024 data from hospitalized kidney failure patients with heart failure showed midodrine use was associated with increased 6-month mortality (RR 1.53, HR 1.54) 3
• Even patients with less severe heart failure warrant cautious approach given potential harm from vasoconstriction 2
• In cardiac amyloidosis patients, severe autonomic dysfunction requiring midodrine that cannot be weaned represents a neurologic contraindication to heart transplantation 2

Cardiac Conduction Abnormalities

Avoid midodrine in patients with significant bradycardia or those on multiple negative chronotropic agents. 4

• Midodrine causes reflex parasympathetic (vagal) stimulation leading to bradycardia through baroreceptor activation in response to increased blood pressure 4, 5
• Concomitant use with beta-blockers, digoxin, or non-dihydropyridine calcium channel blockers significantly increases bradycardia risk 4
• The European Heart Journal notes that agents causing bradycardia may be particularly problematic in cardioinhibitory forms of neurally-mediated syncope 5

Drug Interactions Requiring Avoidance

Do not use midodrine concurrently with other alpha-adrenergic agonists, as this aggravates supine hypertension. 4

• Avoid concomitant use with ephedrine, pseudoephedrine, or phenylpropanolamine 4
• Use caution with alpha-adrenergic blockers (terazosin, prazosin, doxazosin) as midodrine may antagonize their effects and potentially cause urinary retention 4

Critical Safety Monitoring Requirements

Supine Hypertension

Supine hypertension occurs in up to 25% of patients and represents the primary safety concern requiring cessation of therapy. 4, 2

• Monitor blood pressure in both supine and standing positions regularly 4
• Avoid doses within 4 hours of bedtime to minimize supine hypertension risk 2, 6
• Consider elevating head of bed 10 degrees during sleep 5
• Long-term therapy requires ongoing monitoring as supine hypertension occurs in <10% of patients on chronic therapy 4

Urinary Retention Risk

Patients with prostatic hypertrophy or predisposition to urinary retention should be monitored closely, as midodrine can precipitate or worsen retention. 4, 7

• Urinary urgency or retention is a common side effect requiring assessment 4
• The alpha-1 agonist effects on bladder neck can exacerbate obstructive symptoms 4

Common Pitfalls and Clinical Caveats

• Midodrine is not a cure but symptomatic treatment for orthostatic hypotension, requiring ongoing reassessment of need 4
• Hemodialysis patients require special attention as midodrine is effectively cleared during dialysis (half-life reduced to 1.4 hours), necessitating timing doses within 30 minutes of dialysis initiation 4, 5
• Dose reduction required in patients with creatinine clearance <30 mL/min or receiving hemodialysis 4
• The combination of increased afterload and beta-blocker use can unmask subclinical left ventricular dysfunction, potentially showing reduced ejection fraction on echocardiography 5