Droxidopa Availability in Canada for Parkinson's Disease with Neurogenic Orthostatic Hypotension
Droxidopa is NOT approved by Health Canada and cannot be prescribed through standard Canadian channels for Parkinson's disease patients with neurogenic orthostatic hypotension. 1
Regulatory Status in Canada
Only midodrine and fludrocortisone are listed as approved pharmacologic treatments for orthostatic hypotension in Canadian guidelines; droxidopa is mentioned solely in the context of U.S. FDA approval. 1
Droxidopa has FDA approval in the United States for symptomatic neurogenic orthostatic hypotension but has not received Health Canada regulatory approval. 1
Access Through Special Access Programme
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 (midodrine, fludrocortisone) have failed, are unsuitable, or unavailable. 1
This requires physician application demonstrating that standard approved therapies are inadequate for the specific patient. 1
Standard First-Line Treatment in Canada
Midodrine (Primary Recommendation)
Midodrine (initial 2.5–5 mg three times daily, titrated up to 10 mg) is the first-line pressor agent in Canada, supported by three randomized, placebo-controlled trials demonstrating efficacy in neurogenic orthostatic hypotension. 1
Midodrine has the strongest evidence base among pressor agents for orthostatic hypotension. 2
The last dose must be taken at least 4 hours before bedtime (not later than 6 PM) to reduce the risk of supine hypertension during sleep. 1
Fludrocortisone (Alternative or Combination)
Fludrocortisone (0.05–0.1 mg daily, titrated to 0.1–0.3 mg) can be used as monotherapy or combined with midodrine. 1
When monotherapy does not achieve adequate symptom control, combining midodrine with fludrocortisone is recommended because the agents act via complementary mechanisms (α1-adrenergic vasoconstriction vs. mineralocorticoid-mediated volume expansion). 1
Monitor for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema when using fludrocortisone. 2
Refractory Cases
- Pyridostigmine (60 mg three times daily) may be added for patients who remain symptomatic despite midodrine and fludrocortisone, particularly when supine hypertension is a concern, as it does not exacerbate supine blood pressure. 1
Non-Pharmacologic Management (Essential Adjuncts)
Increase fluid intake to 2–3 L per day and dietary sodium to 6–9 g per day, unless contraindicated by heart failure or uncontrolled hypertension. 2, 1
Teach physical counter-pressure maneuvers (leg crossing, squatting, muscle tensing) during symptomatic episodes. 2, 1
Use waist-high compression garments (30–40 mmHg) and abdominal binders to reduce venous pooling. 1
Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria and ameliorate nocturnal hypertension. 1
Encourage physical activity and exercise to avoid deconditioning, which exacerbates orthostatic intolerance. 2
Important Monitoring Considerations
The therapeutic goal is to minimize postural symptoms and improve functional quality of life rather than to normalize blood pressure. 1
All pressor agents can precipitate supine hypertension; regular monitoring of both supine and standing blood pressures is required. 1
Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes. 1
Clinical Context
While droxidopa has demonstrated efficacy in U.S. trials for Parkinson's disease patients with neurogenic orthostatic hypotension—improving symptom scores, standing blood pressure, and quality of life measures 3, 4, 5—Canadian physicians must rely on the approved agents (midodrine and fludrocortisone) as standard therapy, reserving the Special Access Programme for exceptional cases where these fail.