What is the treatment approach for patients with neurogenic orthostatic hypotension (NOH) using Droxidopa?

Treatment Approach for Neurogenic Orthostatic Hypotension Using Droxidopa

Droxidopa is beneficial for patients with symptomatic neurogenic orthostatic hypotension (nOH) due to primary autonomic failure, including Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. 1, 2

Dosing and Administration Protocol

• Starting dose: 100 mg orally three times daily (upon waking, at midday, and late afternoon) 2
• Titration: Increase by 100 mg three times daily every 24-48 hours 2
• Maximum dose: 600 mg three times daily (1,800 mg total daily) 2
• Timing: Administer at least 3 hours before bedtime to reduce risk of supine hypertension 2
• Consistency: Take consistently with or without food 2
• Administration: Take capsules whole 2

Monitoring Requirements

1. Blood pressure monitoring:

   • Measure supine blood pressure before initiating treatment 2
   • Monitor blood pressure after each dose increase 2
   • Check both supine and standing positions 3
   • Assess for supine hypertension, especially when increasing doses 2

2. Efficacy assessment:

   • Evaluate symptom improvement rather than absolute BP values 3
   • Reassess continued effectiveness periodically (effectiveness beyond 2 weeks has not been established) 2, 4
   • Monitor for improvement in orthostatic symptoms (dizziness, lightheadedness, visual disturbances) 1

Managing Supine Hypertension

Supine hypertension is the most significant concern with droxidopa therapy:

• Prevention: Elevate head of bed when resting or sleeping 2
• Monitoring: Regular supine blood pressure checks 2
• Management: If supine hypertension persists despite head elevation, reduce dose or discontinue droxidopa 2
• Timing: Last dose should be taken at least 3-4 hours before bedtime 3, 2

Special Considerations

1. Parkinson's disease patients:

   • Carbidopa may decrease effectiveness of droxidopa 1
   • Monitor for hyperpyrexia and confusion when changing droxidopa dose or reducing levodopa 2

2. Cardiac conditions:

   • Use with caution in patients with ischemic heart disease, arrhythmias, or heart failure 2
   • Careful consideration of risks before initiating therapy 2

3. Efficacy duration:

   • Short-term efficacy (up to 2 weeks) is well-established 4
   • Long-term efficacy data is limited; efficacy may decrease after 2 weeks 4
   • Regular reassessment of continued effectiveness is essential 2

Alternative and Adjunctive Treatments

If droxidopa is insufficient or contraindicated, consider:

1. Other pharmacological options:

   • Midodrine: Alpha-1 agonist, 5-20mg three times daily 1, 3
   • Fludrocortisone: Mineralocorticoid, 0.1mg daily, especially with increased salt intake 1, 3
   • Pyridostigmine: For refractory cases, 30mg 2-3 times daily 1, 3

2. Non-pharmacological measures (should be used alongside droxidopa):

   • Increased salt (6-9g daily) and fluid intake (2-3L/day) 1, 3
   • Compression garments (at least thigh-high) 1
   • Physical counter-pressure maneuvers 1
   • Acute water ingestion (480mL) for temporary relief 1
   • Small, frequent meals with reduced carbohydrate content 3

Efficacy Evidence

Droxidopa has shown significant improvements in:

• Orthostatic Hypotension Questionnaire (OHQ) composite scores 5, 6
• Dizziness/lightheadedness symptoms 5, 6
• Standing systolic blood pressure 5, 6
• Ability to perform activities requiring standing 7, 6

However, efficacy may diminish over time, with statistical significance lost after 8 weeks in some studies 4.

Common Pitfalls to Avoid

• Focusing on BP numbers rather than symptom improvement 3
• Administering too close to bedtime, increasing risk of supine hypertension 3, 2
• Inadequate monitoring for supine hypertension 3, 2
• Failure to reassess continued effectiveness periodically 2
• Overlooking drug interactions, particularly with carbidopa in Parkinson's disease 1

Droxidopa is generally well-tolerated with headache (7.4%) and dizziness (3.7%) being the most common adverse events 5.