What are the side effects of midodrine?

Side Effects of Midodrine

The most common side effects of midodrine are supine hypertension (occurring in up to 25% of patients), pilomotor reactions (piloerection, scalp pruritus/tingling), urinary symptoms (urgency, retention, frequency), and reflex bradycardia from vagal stimulation. 1, 2

Most Frequent Adverse Effects

Cardiovascular Side Effects

• Supine hypertension is the most potentially serious adverse reaction, occurring in up to 25% of patients on long-term therapy, and can be minimized by avoiding doses within 4 hours of bedtime and sleeping with the head of bed elevated at 10 degrees 1, 3, 2, 4
• Reflex bradycardia occurs through parasympathetic (vagal) stimulation in response to midodrine's alpha-1 adrenergic-mediated increase in peripheral vascular resistance and blood pressure 1, 3
• Patients on negative chronotropic agents (beta-blockers, non-dihydropyridine calcium channel blockers) require cautious co-administration due to enhanced risk of bradycardia 1, 3, 5

Pilomotor Reactions (Alpha-Adrenergic Effects on Hair Follicles)

• Piloerection (goosebumps) occurs in 13.4% of patients 2
• Scalp pruritus/tingling occurs in 12.2-13.5% of patients 2, 6
• Paresthesia (including scalp hyperesthesia) occurs in 18.3% of patients 2
• Chills occur in 4.9% of patients 2

Urinary Symptoms (Alpha-Receptor Effects on Bladder Neck)

• Urinary urgency, retention, and frequency occur in 13.4% of patients, associated with midodrine's action on alpha-receptors of the bladder neck 2, 6
• Dysuria occurs in 13.4% of patients 2

Gastrointestinal Effects

• Nausea, heartburn (pyrosis), and gastrointestinal distress are common side effects requiring monitoring 5, 2
• Dry mouth, flatulence, and abdominal pain occur less frequently 2

Less Common Side Effects

• Headache, feeling of pressure/fullness in the head 5, 2
• Vasodilation/flushing of face 2
• Nervousness/anxiety, confusion/thinking abnormality 5, 2
• Sleep disturbance, insomnia, somnolence 5, 2
• Rash (2.4% of patients), dry skin, erythema multiforme 2
• Dizziness, visual field defect 2
• Asthenia, backache, leg cramps 2

Critical Monitoring Parameters and Withhold Criteria

When to Withhold Midodrine

• Withhold midodrine if supine systolic hypertension develops or if bradycardia occurs, as these are the primary safety concerns requiring cessation of therapy 5
• Monitor blood pressure in both supine and standing positions to assess efficacy and detect supine hypertension 5
• Assess for urinary retention regularly 5

Special Population Considerations

• Midodrine may be poorly tolerated in heart failure patients and should be used with extreme caution, as increased afterload may unmask or worsen subclinical left ventricular dysfunction 3
• Hemodialysis patients warrant particular attention for bradycardia monitoring 1, 3
• The combination of midodrine and beta-blockers can lead to more pronounced bradycardia and potentially reduced ejection fraction 1

Drug Interactions Increasing Side Effect Risk

• Concomitant use with other alpha-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) may aggravate supine hypertension 5
• Alpha-adrenergic blockers (terazosin, prazosin, doxazosin) may be antagonized by midodrine and potentially cause urinary retention 5
• Negative chronotropic agents increase bradycardia risk 3, 5

Common Pitfalls to Avoid

• The most critical pitfall is administering doses too close to bedtime, which significantly increases supine hypertension risk; the last dose should be no later than 6 PM 1
• Failure to monitor for bradycardia in patients on beta-blockers or other rate-controlling medications 1, 3
• Not recognizing that side effects are generally mild to moderate and can often be controlled by reducing the dosage rather than discontinuing therapy 7
• Overlooking that pilomotor reactions (piloerection, scalp tingling, chills) are directly related to alpha-adrenergic receptor stimulation of hair follicles and are expected pharmacologic effects rather than allergic reactions 2