Midodrine Side Effects
Midodrine commonly causes several side effects including piloerection (goosebumps), scalp itching/tingling, urinary issues, and supine hypertension, with the latter being potentially the most serious adverse effect requiring monitoring. 1, 2
Common Side Effects
Midodrine's side effects can be categorized by frequency and severity:
Very Common Side Effects (>10%)
- Piloerection (goosebumps) - 13.4% 2
- Paresthesia/tingling (especially scalp) - 18.3% 2
- Urinary issues (urgency, retention, frequency) - 13.4% 2
- Pruritus (itching) - 12.2% 2
Common Side Effects (1-10%)
- Supine hypertension - 7.3% 2, up to 25% in some studies 3
- Chills - 4.9% 2
- Pain - 4.9% 2
- Headache/feeling of pressure in head 2
Less Common Side Effects
- Rash
- Dry mouth
- Nervousness/anxiety
- Visual field defects
- Dizziness
- Insomnia/somnolence
- Gastrointestinal distress (nausea, pyrosis, flatulence)
- Asthenia
- Backache 2
Serious Side Effects
Supine Hypertension
This is the most potentially serious adverse reaction associated with midodrine therapy 1, 2:
- Systolic pressures of approximately 200 mmHg seen in about 13.4% of patients given 10 mg
- More likely in patients with elevated pre-treatment systolic blood pressure
- Not recommended for patients with initial supine systolic pressure above 180 mmHg
- Risk can be reduced by taking the final daily dose at least 4 hours before bedtime 3
Bradycardia
Patients should be monitored for bradycardia as midodrine is associated with reflex parasympathetic stimulation 1.
Mechanism of Side Effects
Many of midodrine's side effects are directly related to its alpha-1-adrenergic activity:
- Pilomotor reactions (piloerection, pruritus, chills) are associated with the action of midodrine on alpha-adrenergic receptors of hair follicles 2
- Urinary symptoms result from increased tone of the vesical sphincter due to alpha-1-adrenergic effects 4
Special Precautions and Drug Interactions
Midodrine should be used cautiously in:
- Patients with CHF
- Patients using other negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) 1
Avoid concomitant use with:
- Other alpha-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) as this may aggravate supine hypertension
- May antagonize alpha-adrenergic blockers (terazosin, prazosin, doxazosin) and could result in urinary retention 1
Rare but Notable Side Effects
- Urologic adverse effects may develop insidiously in patients with spinal cord injury, potentially leading to hydroureteronephrosis 4
- Nightmares have been reported as a novel side effect, particularly with evening dosing 5
Monitoring Recommendations
- Regular blood pressure monitoring in both supine and sitting positions is essential 2
- Monitor for urinary retention, especially in patients with pre-existing urologic conditions 4
- Watch for bradycardia in patients on concomitant negative chronotropic medications 1
For patients on dialysis, both the prodrug and active metabolite are removed effectively by hemodialysis, reducing the risk of developing supine hypertension 1.