What are the complications of Midodrine (Midodrine hydrochloride)?

Complications of Midodrine

Midodrine can cause significant supine hypertension in up to 13.4% of patients, with systolic pressures reaching approximately 200 mmHg, which is the most serious potential adverse reaction requiring careful blood pressure monitoring. 1

Common Side Effects

• Cardiovascular complications:

  • Supine and sitting hypertension (7.3% in clinical trials) 1
  • Bradycardia due to reflex parasympathetic stimulation 2
  • Risk of supine hypertension can persist for extended periods - in pediatric cases, it has been documented to continue for up to 19 days after discontinuation 3

• Neurological and sensory effects:

  • Paresthesia (18.3%), particularly scalp paresthesia 1
  • Piloerection/goosebumps (13.4%) 1
  • Scalp itching/pruritus (12.2%) 1
  • Chills (4.9%) 1
  • Headache 1
  • Nightmares (rare but documented case reports) 4

• Urinary complications:

  • Urinary urgency, retention, and frequency (13.4%) 1
  • These effects are associated with midodrine's action on alpha-receptors of the bladder neck 1

• Gastrointestinal effects:

  • Nausea and heartburn 2, 1
  • Gastrointestinal distress 1

• Other reported effects:

  • Sleep disturbance 2
  • Nervousness 2
  • Visual field defects (rare) 1
  • Dry mouth 1
  • Erythema multiforme (rare) 1

Risk Factors and Special Populations

• Patients with elevated baseline blood pressure:

  • Those with pre-treatment systolic blood pressures around 170 mmHg are at higher risk for severe supine hypertension 1
  • Midodrine is not recommended for patients with initial supine systolic pressure above 180 mmHg 1

• Patients with congestive heart failure:

  • Midodrine should be used cautiously in these patients 2

• Patients on other medications:

  • Caution with concomitant use of negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) 2
  • Avoid combination with other alpha-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) as this may worsen supine hypertension 2
  • Can antagonize actions of alpha-adrenergic blockers (terazosin, prazosin, doxazosin) potentially resulting in urinary retention 2

• Dialysis patients:

  • Midodrine is effectively cleared by hemodialysis with half-life reduced to 1.4 hours 2
  • Risk of developing supine hypertension is possible but rare in dialysis patients 2

Monitoring and Management

• Blood pressure monitoring:

  • Essential to monitor both supine and sitting blood pressures in all patients on midodrine 1
  • Uncontrolled hypertension increases risk of cardiovascular events, particularly stroke 1

• Dosing considerations:

  • Final daily dose should be taken at least 4 hours before bedtime to reduce risk of supine hypertension 5
  • For orthostatic hypotension, dosing should be individually tailored (up to 10 mg 2-4 times daily) 2

• When to discontinue:

  • Long-term use associated with supine systolic hypertension in <10% of patients; this side effect warrants cessation of therapy 2

Specific Clinical Contexts

• In dialysis patients:

  • Midodrine is used to prevent intradialytic hypotension 2
  • Both prodrug and active metabolite are removed effectively by hemodialysis 2
  • Combination of cool dialysate and predialysis doses of midodrine may decrease frequency and intensity of intradialytic hypotension symptoms without increasing side effects 2

• In cirrhotic patients with ascites:

  • Used as a vasoconstrictor to help manage refractory ascites 2, 6
  • Small studies show potential benefits, but larger trials are needed 2

• In orthostatic hypotension:

  • First-line drug for symptomatic orthostatic hypotension 2
  • Generally well-tolerated compared to other sympathomimetic agents 7
  • Side effects can often be controlled by reducing the dosage 7