Can droxidopa be prescribed in Canada for adult patients with symptomatic neurogenic orthostatic hypotension due to primary autonomic failure (e.g., Parkinson disease, multiple system atrophy, pure autonomic failure, dopamine‑β‑hydroxylase deficiency, non‑diabetic autonomic neuropathy), and how is it accessed?

Droxidopa Availability and Access in Canada

Droxidopa is FDA-approved in the United States for symptomatic neurogenic orthostatic hypotension but is NOT approved by Health Canada and therefore cannot be prescribed through standard channels in Canada. 1, 2

Regulatory Status

• Droxidopa received FDA approval in the United States in February 2014 for treatment of symptomatic neurogenic orthostatic hypotension (nOH) due to primary autonomic failure (Parkinson disease, multiple system atrophy, pure autonomic failure), dopamine β-hydroxylase deficiency, and non-diabetic autonomic neuropathy. 3

• The medication has regulatory approval for orthostatic hypotension in both the U.S. and Canada according to tapentadol context, but droxidopa itself is only mentioned as FDA-approved in all guideline sources without specific Health Canada approval documentation. 1

• In Canada, the only explicitly approved medications for orthostatic hypotension mentioned in guidelines are midodrine and fludrocortisone, with droxidopa referenced only in the context of U.S. FDA approval. 1, 2

Alternative Access Pathways in Canada

• Canadian patients may potentially access droxidopa through Health Canada's Special Access Programme (SAP), which allows practitioners to request access to non-approved drugs for patients with serious or life-threatening conditions when conventional therapies have failed, are unsuitable, or are unavailable. (General medical knowledge)

• Cross-border prescription filling or importation for personal use may be possible under specific circumstances, though this requires navigation of both Canadian and U.S. regulatory frameworks. (General medical knowledge)

Approved Treatment Options in Canada

For Canadian patients with symptomatic neurogenic orthostatic hypotension, the following FDA/Health Canada-approved pharmacological options should be considered:

First-Line Pharmacological Therapy

• Midodrine (2.5-5 mg three times daily, titrated up to 10 mg) is the first-line pressor agent with the strongest evidence base, including three randomized placebo-controlled trials demonstrating efficacy. 1, 2

• The last dose of midodrine must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 2

• Fludrocortisone (0.05-0.1 mg daily, titrated to 0.1-0.3 mg daily) acts through sodium retention and vessel wall effects and can be used as monotherapy or in combination with midodrine. 1, 2

Combination Therapy

• For patients inadequately controlled on monotherapy, combining midodrine with fludrocortisone is recommended, as they work through complementary mechanisms (α1-adrenergic vasoconstriction versus mineralocorticoid-mediated volume expansion). 1, 2

Refractory Cases

• Pyridostigmine (60 mg three times daily) may be beneficial in patients refractory to midodrine and fludrocortisone, particularly when supine hypertension is a concern, as it does not worsen supine blood pressure. 1, 2

Non-Pharmacological Management (Essential Adjuncts)

• Increase fluid intake to 2-3 liters daily and salt intake to 6-9 grams daily unless contraindicated by heart failure or uncontrolled hypertension. 1, 2

• Physical counter-pressure maneuvers (leg crossing, squatting, muscle tensing) should be taught and performed during symptomatic episodes. 1, 2

• Compression garments (waist-high, 30-40 mmHg) and abdominal binders reduce venous pooling. 1, 2

• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria and ameliorate supine hypertension. 2

Clinical Evidence for Droxidopa (U.S. Context)

• Droxidopa improved dizziness/lightheadedness scores and standing systolic blood pressure by 11.2 mm Hg versus 3.9 mm Hg with placebo in a phase 3 randomized controlled trial (Class I evidence). 4

• The number needed to treat (NNT) for droxidopa was less than 10, with a number needed to harm (NNH) for adverse events leading to discontinuation of 81, indicating droxidopa is 7.8 times more likely to provide clinical benefit than cause discontinuation. 5

• Common adverse effects include headache (7.4%), dizziness (3.7%), and potential supine hypertension, with supine systolic BP >180 mm Hg observed in 4.9% of patients. 4, 3

Important Caveats

• Use of carbidopa in patients with Parkinson disease may decrease the effectiveness of droxidopa by blocking peripheral conversion to norepinephrine. 1

• The therapeutic goal is minimizing postural symptoms rather than restoring normotension, and treatment should focus on functional improvement and quality of life. 1, 2

• All pressor agents (midodrine, droxidopa, fludrocortisone) can cause supine hypertension, requiring regular monitoring of both supine and standing blood pressure. 1, 2