What is the recommended treatment and dosage of Droxidopa (Northera) for neurogenic orthostatic hypotension (NOH)?

Droxidopa Treatment for Neurogenic Orthostatic Hypotension (NOH)

Droxidopa (Northera) is recommended at an initial dose of 100 mg three times daily, titrated up to a maximum of 600 mg three times daily (1,800 mg total daily dose) for patients with symptomatic neurogenic orthostatic hypotension. 1, 2

Dosing Protocol

Initial Dosing and Titration

• Start with 100 mg orally three times daily
• Administer at specific times:
  • Upon waking in the morning
  • At midday
  • Late afternoon (at least 3 hours before bedtime to reduce risk of supine hypertension)
• Titrate dose in increments of 100 mg three times daily every 24-48 hours
• Maximum dose: 600 mg three times daily (1,800 mg total daily dose)
• Take consistently with or without food
• Swallow capsules whole

Monitoring and Dose Adjustment

• Monitor supine blood pressure before initiating treatment and after each dose increase
• Assess effectiveness based on symptom improvement rather than blood pressure normalization
• Evaluate continued effectiveness periodically (FDA label notes effectiveness beyond 2 weeks has not been established, though recent studies support longer efficacy) 2, 3

Patient Selection

Droxidopa is specifically indicated for:

• Adults with symptomatic neurogenic orthostatic hypotension caused by:
  • Primary autonomic failure (Parkinson's disease, multiple system atrophy, pure autonomic failure)
  • Dopamine beta-hydroxylase deficiency
  • Non-diabetic autonomic neuropathy 2

Clinical Efficacy

Droxidopa improves:

• Orthostatic symptoms (dizziness/lightheadedness)
• Activities of daily living
• Standing systolic blood pressure
• May reduce falls according to small studies 1, 4

In a randomized controlled trial, droxidopa demonstrated:

• Significant improvement in Orthostatic Hypotension Questionnaire (OHQ) composite score
• Mean standing systolic BP increase of 11.2 mmHg vs 3.9 mmHg with placebo
• Maximum benefit for symptoms of "dizziness/lightheadedness" 4

A 12-week open-label study showed sustained efficacy with:

• Significant improvements in symptoms and activities of daily living
• Mean supine systolic BP increase of 15.5 mmHg 3

Precautions and Monitoring

Supine Hypertension

• Critical safety concern: Monitor supine blood pressure before and during treatment
• Elevate head of bed during sleep (reduces risk of supine hypertension)
• Measure blood pressure in head-elevated position
• If supine hypertension cannot be managed by elevation of the head of the bed, reduce or discontinue droxidopa 2
• Supine hypertension may increase cardiovascular risk, particularly stroke 2

Other Precautions

• Use with caution in patients with:
  • Existing ischemic heart disease
  • Arrhythmias
  • Congestive heart failure
• May be poorly tolerated in heart failure patients 1
• Carbidopa use in Parkinson's disease patients may decrease droxidopa effectiveness 1

Common Adverse Effects

• Headache (7.4%)
• Dizziness (3.7%)
• Nausea
• Hypertension 2, 4

Alternative and Adjunctive Treatments

If droxidopa is ineffective or contraindicated, consider:

Other Pharmacologic Options

• Midodrine (2.5-10 mg three times daily)
• Fludrocortisone (0.1-1.0 mg daily) - use cautiously in heart failure
• Pyridostigmine (30-60 mg 2-3 times daily) - less likely to cause supine hypertension 1

Non-Pharmacologic Approaches

1. Acute water ingestion (≥240 mL, peak effect at 30 minutes)
2. Physical counter-pressure maneuvers (leg crossing, lower body muscle tensing)
3. Compression garments (at least thigh-high, preferably including abdomen)
4. Increased salt intake (6-9 g daily) and fluid intake
5. Elevating head of bed during sleep 1

Treatment Algorithm

1. First-line: Non-pharmacologic measures (compression garments, increased salt/fluid intake, physical counter-maneuvers)
2. Second-line: Initiate droxidopa at 100 mg three times daily
3. Titration: Increase by 100 mg three times daily every 24-48 hours based on symptom response
4. Monitoring: Check supine blood pressure before each dose increase
5. Maximum dose: 600 mg three times daily if needed and tolerated
6. Reassessment: Evaluate continued effectiveness periodically

Special Considerations

• Ambulatory blood pressure monitoring may be useful to evaluate the circadian BP profile and detect nocturnal hypertension 5
• Approximately 22% of patients may experience nocturnal BP increases ≥10 mmHg 5
• Droxidopa is contraindicated in patients with history of hypersensitivity to the drug or its ingredients 2