What medications are approved in Canada for the treatment of neurogenic orthostatic hypotension?

Approved Medications for Neurogenic Orthostatic Hypotension in Canada

In Canada, only midodrine and fludrocortisone are approved for treating neurogenic orthostatic hypotension; droxidopa remains FDA-approved in the United States but has not received Health Canada approval and can only be accessed through the Special Access Programme for refractory cases. 1

First-Line Pharmacologic Options in Canada

Midodrine (Primary Recommendation)

Midodrine is the first-line pressor agent with the strongest evidence base, supported by three randomized placebo-controlled trials demonstrating efficacy in neurogenic orthostatic hypotension. 1, 2

• Start at 2.5–5 mg three times daily, taken at approximately 4-hour intervals during daytime hours when upright activity is needed 3, 1
• Titrate up to 10 mg three times daily based on symptom response and tolerability 3, 1, 4
• Administer the last dose at least 3–4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1, 5
• Midodrine increases standing systolic blood pressure by 15–30 mmHg for 2–3 hours through peripheral α1-adrenergic vasoconstriction 1

Fludrocortisone (Alternative or Combination Agent)

Fludrocortisone can be used as monotherapy or combined with midodrine when single-agent therapy provides insufficient symptom control. 3, 1

• Start at 0.05–0.1 mg once daily, titrate to 0.1–0.3 mg daily based on response 3, 1
• Acts through sodium retention and vessel wall effects to expand plasma volume 3, 1
• Monitor for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema 3, 1
• Avoid in patients with active heart failure or severe renal disease where sodium retention would be harmful 1

Combination Therapy for Inadequate Response

When monotherapy does not achieve adequate symptom control, combining midodrine with fludrocortisone is recommended because the agents act via complementary mechanisms (α1-adrenergic vasoconstriction versus mineralocorticoid-mediated volume expansion). 3, 1

• Midodrine provides direct vascular constriction while fludrocortisone increases plasma volume through sodium retention 1, 5
• This combination is supported by guideline recommendations for non-responders to monotherapy 3, 1

Refractory Cases: Pyridostigmine

For patients who remain symptomatic despite midodrine and fludrocortisone, pyridostigmine (60 mg three times daily) may be added, particularly when supine hypertension is a concern, as it does not exacerbate supine blood pressure. 3, 1

• Pyridostigmine works by inhibiting acetylcholinesterase, enhancing ganglionic sympathetic transmission 1
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence 3, 1
• This agent is preferred when supine hypertension limits the use of other pressor agents 1

Accessing Droxidopa in Canada

Droxidopa is FDA-approved in the United States for symptomatic neurogenic orthostatic hypotension but has not received Health Canada approval and cannot be prescribed through standard Canadian channels. 1

• Health Canada's Special Access Programme (SAP) can be used to obtain droxidopa for patients with serious or life-threatening neurogenic orthostatic hypotension when conventional therapies have failed, are unsuitable, or unavailable 1
• Droxidopa is particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 3, 1
• Carbidopa therapy in patients with Parkinson disease may diminish the effectiveness of droxidopa by inhibiting peripheral conversion to norepinephrine 1

Essential Non-Pharmacologic Adjuncts

Non-pharmacological measures should be implemented first or concurrently with pharmacologic therapy, as they form the foundation of orthostatic hypotension management. 3, 1

• Increase fluid intake to 2–3 liters daily and dietary sodium to 6–9 grams daily, unless contraindicated by heart failure or uncontrolled hypertension 3, 1
• Teach physical counter-pressure maneuvers (leg crossing, squatting, stooping, muscle tensing) for use during symptomatic episodes 3, 1
• Use waist-high compression garments (30–40 mmHg) and abdominal binders to reduce venous pooling 3, 1
• Elevate the head of the bed by approximately 10 degrees to prevent nocturnal polyuria and ameliorate nocturnal hypertension 3, 1
• Advise acute water ingestion (≥480 mL) for temporary relief, with peak effect occurring 30 minutes after consumption 3, 1

Critical Monitoring Requirements

Monitor both supine and standing blood pressure at each visit by measuring after 5 minutes lying/sitting, then at 1 minute and 3 minutes after standing. 3, 1

• All pressor agents (midodrine, fludrocortisone) can precipitate supine hypertension; regular monitoring is required 1
• Check electrolytes periodically when using fludrocortisone due to mineralocorticoid effects that can cause potassium wasting 1
• The therapeutic goal is to minimize postural symptoms and improve functional quality of life rather than to normalize blood pressure 3, 1, 2

Common Pitfalls to Avoid

• Do not administer midodrine after 6 PM, as late dosing heightens nocturnal orthostatic risk and supine hypertension 1, 5
• Avoid concomitant use of midodrine with other α-adrenergic agents (ephedrine, pseudoephedrine, phenylpropanolamine) as this may aggravate supine hypertension 5, 4
• Use midodrine cautiously with negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) 5, 4
• Do not use fludrocortisone in patients with heart failure or supine hypertension 1
• Midodrine can antagonize alpha-adrenergic blockers (terazosin, prazosin, doxazosin) and could result in urinary retention 4