When should midodrine be started in patients with orthostatic hypotension?

From the Guidelines

Midodrine should be started in patients with orthostatic hypotension when non-pharmacological measures have failed to adequately control symptoms, as recommended by the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1.

Key Considerations

• Non-pharmacological measures, such as increasing fluid intake, adding salt to the diet, wearing compression stockings, and practicing physical countermaneuvers, should be tried first to control symptoms.
• Midodrine works by stimulating alpha-1 adrenergic receptors, causing arterial and venous constriction, which increases blood pressure and helps reduce symptoms like dizziness, lightheadedness, and syncope upon standing.
• The typical starting dose of midodrine is 2.5 mg three times daily, which can be titrated up to 10 mg three times daily based on symptom response and tolerability.
• Doses should be taken upon waking, at midday, and in the late afternoon (no later than 6 PM) to avoid supine hypertension while sleeping.

Potential Side Effects and Contraindications

• Patients should be monitored for potential side effects including supine hypertension, urinary retention, piloerection (goosebumps), and scalp tingling.
• Midodrine is contraindicated in patients with severe cardiac disease, acute renal failure, urinary retention, pheochromocytoma, and thyrotoxicosis.

Additional Recommendations

• Other treatments, such as fludrocortisone, droxidopa, and pyridostigmine, may be considered in patients with neurogenic orthostatic hypotension, as recommended by the 2017 ACC/AHA/HRS guideline 1.
• Physical counter-pressure maneuvers, compression garments, and increased salt and fluid intake may also be beneficial in patients with orthostatic hypotension, as recommended by the 2017 ACC/AHA/HRS guideline 1.

From the FDA Drug Label

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH) Because midodrine hydrochloride tablets can cause marked elevation of supine blood pressure (BP>200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations After initiation of treatment, midodrine hydrochloride tablets should be continued only for patients who report significant symptomatic improvement.

Midodrine should be started in patients with orthostatic hypotension whose lives are considerably impaired despite standard clinical care. The treatment should be initiated when patients have not responded to non-pharmacologic treatments, such as:

• Support stockings
• Fluid expansion
• Lifestyle alterations It is essential to monitor the patient's response to midodrine and continue treatment only if significant symptomatic improvement is reported 2.

From the Research

Initiating Midodrine in Orthostatic Hypotension

• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration 3.
• The decision to start midodrine in patients with orthostatic hypotension should be based on the severity of symptoms and the failure of nonpharmacological measures, as it is considered a therapeutic option for the management of various forms of orthostatic hypotension 3, 4.
• Midodrine has been shown to increase standing blood pressure and improve symptoms of orthostatism, such as weakness, syncope, blurred vision, and fatigue, without any associated cardiac stimulation 4.
• The risk of supine hypertension, which is associated with midodrine therapy in up to 25% of patients, can be reduced by taking the final daily dose at least 4 hours before bedtime 3.

Clinical Benefit of Midodrine

• Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension, and has been shown to be clinically effective in a phase 4, double-blind, placebo-controlled, randomized, tilt-table study 5.
• The study found that midodrine significantly increased the time to syncopal symptoms or near-syncope compared to placebo, with a difference of 521.0 seconds (95% confidence interval 124.2-971.7 seconds; p = 0.0131) 5.
• Midodrine is well-tolerated, with the most commonly reported adverse events being piloerection, pruritus, paraesthesias, urinary retention, and chills 3, 4.

Comparison with Other Treatments

• Midodrine has been compared to other treatments for orthostatic hypotension, including fludrocortisone, and has been found to be at least as effective in improving symptoms and increasing blood pressure 3, 6, 7.
• The choice of treatment should be guided by patient-specific factors, such as tolerability, adverse effects, and drug-drug and drug-disease interactions 7.