What are the side effects of midodrine?

Side Effects of Midodrine

The most potentially serious adverse reaction associated with midodrine is supine hypertension, which occurs in up to 25% of patients, while the most common side effects include pilomotor reactions (piloerection, scalp pruritus/tingling), paresthesias, urinary symptoms (urgency, retention, frequency), and bradycardia. 1

Most Serious Adverse Effect: Supine Hypertension

Supine hypertension represents the primary safety concern requiring careful monitoring and potential discontinuation of therapy. 1

• Marked elevation of supine arterial blood pressure occurs in approximately 13.4% of patients receiving 10 mg doses, with systolic pressures reaching about 200 mmHg in some cases 1
• The risk is highest in patients with relatively elevated pre-treatment systolic blood pressures (mean 170 mmHg) 1
• Both supine and sitting blood pressures are elevated by midodrine therapy 1
• To minimize this risk, avoid doses within at least 4 hours before bedtime, and sleep with the head of bed elevated at 10 degrees 2, 3
• Essential monitoring includes regular assessment of both supine and standing blood pressures 4

Common Side Effects

Pilomotor Reactions (Alpha-Adrenergic Effects on Hair Follicles)

• Piloerection (goosebumps) occurs in 13.4% of patients 1
• Scalp pruritus/tingling affects 12.2-13.5% of patients 1, 5
• Paresthesia (including scalp hyperesthesia) occurs in 18.3% of patients 1
• Chills affect 4.9% of patients 1

These pilomotor reactions are directly associated with midodrine's action on alpha-adrenergic receptors of the hair follicles 1

Urinary Symptoms (Alpha-Receptor Effects on Bladder Neck)

Urinary symptoms result from midodrine's action on alpha-receptors of the bladder neck and can be particularly problematic in certain populations. 1

• Dysuria and urinary retention occur in 13.4% of patients 1
• Urinary urgency and frequency are common complaints 1
• In patients with spinal cord injury who void spontaneously, midodrine can insidiously cause progressive urinary retention and may aggravate detrusor-sphincter dyssynergia, potentially leading to hydroureteronephrosis 6
• If urinary retention develops, consider intermittent catheterization combined with antimuscarinic therapy (e.g., oxybutynin) 6

Cardiovascular Effects

Bradycardia occurs through reflex parasympathetic (vagal) stimulation in response to midodrine's alpha-1 adrenergic-mediated increase in peripheral vascular resistance and blood pressure. 2

• The elevated blood pressure activates arterial baroreceptors, leading to increased vagal tone and bradycardia 2
• Patients on negative chronotropic agents (beta-blockers, non-dihydropyridine calcium channel blockers, digoxin) require cautious co-administration and close monitoring 2, 4
• Hemodialysis patients warrant particular attention for bradycardia monitoring 2, 4

Gastrointestinal and Other Effects

• Pain occurs in 4.9% of patients 1
• Nausea, heartburn, and gastrointestinal distress are reported 4, 1
• Headache, feeling of pressure/fullness in the head 1
• Nervousness/anxiety 1

Less Common but Notable Adverse Effects

• Rash and erythema multiforme (rare) 1
• Visual field defects (rare) 1
• Dizziness, confusion/thinking abnormality 1
• Insomnia, somnolence 1
• Nightmares have been reported in at least one case, potentially related to autonomic dysfunction 7
• Dry mouth, dry skin 1
• Backache, asthenia 1
• Leg cramps, flatulence 1

Special Population Considerations

Heart Failure Patients

Midodrine may be poorly tolerated in heart failure patients and should be used with extreme caution. 8

• The increased systemic vascular resistance shifts blood from peripheral circulation into pulmonary vasculature, potentially increasing left ventricular filling pressures 2
• Increased afterload may unmask or worsen subclinical left ventricular dysfunction 2
• Severe autonomic dysfunction requiring midodrine that cannot be weaned represents a neurologic contraindication to heart transplantation in cardiac amyloidosis patients 8

Hemodialysis Patients

• Midodrine is effectively cleared during dialysis, reducing its half-life to 1.4 hours 2, 4
• The combination of cool dialysate and predialysis midodrine doses may decrease intradialytic hypotension symptoms without significant side effects 4

Critical Monitoring Parameters and Withhold Criteria

Withhold midodrine if the patient develops supine systolic hypertension or significant bradycardia, as these are the primary safety concerns requiring cessation of therapy. 4

• Monitor supine and standing blood pressures regularly 4, 1
• Assess for bradycardia, especially with concomitant negative chronotropic agents 4
• Evaluate for urinary retention 4
• Consider ambulatory blood pressure monitoring to identify abnormal diurnal patterns 2

Drug Interactions Increasing Side Effect Risk

• Concomitant use with other alpha-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) may aggravate supine hypertension 4
• Alpha-adrenergic blockers (terazosin, prazosin, doxazosin) may be antagonized by midodrine and potentially cause urinary retention 4
• Beta-blockers combined with midodrine can lead to more pronounced bradycardia and potentially reduced ejection fraction 2