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 in patients with symptomatic neurogenic orthostatic hypotension (NOH) due to Parkinson's disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy. 1 It improves symptoms and can potentially reduce falls, though its use may be limited by supine hypertension, headache, dizziness, and nausea.

Indications and Patient Selection

• Droxidopa is specifically indicated for treating orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic NOH 2
• Appropriate for patients with NOH caused by:
  • Primary autonomic failure (Parkinson's disease, multiple system atrophy, pure autonomic failure)
  • Dopamine beta-hydroxylase deficiency
  • Non-diabetic autonomic neuropathy 2
• Note: Effectiveness beyond 2 weeks of treatment has not been definitively established 2, 3

Dosing Protocol

1. Starting dose: 100 mg orally three times daily 2

   • Administration times: upon arising in morning, at midday, and late afternoon
   • Last dose should be taken at least 3 hours prior to bedtime to reduce risk of supine hypertension

2. Titration: Increase in increments of 100 mg three times daily every 24-48 hours 2

   • Titrate to symptomatic response
   • Maximum dose: 600 mg three times daily (1,800 mg total daily dose)

3. Administration considerations:

   • Take consistently either with or without food
   • Swallow capsules whole
   • If a dose is missed, take the next scheduled dose (do not double up) 2

Monitoring Requirements

• Blood pressure monitoring:

  • Monitor supine blood pressure prior to initiating treatment
  • Check blood pressure after each dose increase
  • Measure both supine and standing positions 1, 2
  • Evaluate for supine hypertension (BP >180/110 mmHg) 4

• Efficacy assessment:

  • Evaluate based on symptom improvement rather than absolute BP values 4
  • Periodically assess continued effectiveness 2
  • Use patient-reported symptoms as primary indicator of benefit 5

Managing Supine Hypertension

• Elevate the head of the bed when resting or sleeping 2
• If supine hypertension persists despite head elevation, reduce or discontinue droxidopa 2
• Monitor blood pressure in both supine and head-elevated sleeping positions 1
• Be aware that poorly managed supine hypertension may increase cardiovascular risk, particularly stroke 2

Special Considerations

• Parkinson's disease patients: Use of carbidopa may decrease the effectiveness of droxidopa 1
• Cardiac conditions: Use with caution in patients with ischemic heart disease, arrhythmias, or congestive heart failure 2
• Monitoring for hyperpyrexia and confusion: Observe patients carefully when dosage is changed or when concomitant levodopa is reduced/discontinued 2

Combination Therapy Approach

For patients with inadequate response to droxidopa alone, consider a stepwise approach:

1. First optimize non-pharmacological measures:

   • Physical counter-pressure maneuvers (leg crossing, squatting) 1, 4
   • Compression garments (at least thigh-high, preferably including abdomen) 1
   • Increased salt (6-9g daily) and fluid (2-3L daily) intake if not contraindicated 1, 4
   • Small, frequent meals with reduced carbohydrate content 4

2. Consider adding other pharmacological agents if needed:

   • Midodrine (improves symptoms with dose-dependent effect) 1
   • Fludrocortisone (increases plasma volume) 1
   • Pyridostigmine (for patients refractory to other treatments) 1
   • Octreotide (for refractory recurrent postprandial or neurogenic OH) 1

Efficacy and Limitations

• Clinical trials demonstrate that droxidopa improves symptoms and symptom impact on daily activities 5, 6
• Significant improvements in Orthostatic Hypotension Questionnaire scores and standing systolic blood pressure 5, 6
• The efficacy of droxidopa may decrease gradually after 2 weeks, with statistical significance lost after 8 weeks in some studies 3
• Regular assessment of continued effectiveness is necessary 2

Common Pitfalls to Avoid

• Timing errors: Administering the last dose too close to bedtime increases risk of supine hypertension 4
• Inadequate monitoring: Failing to check for supine hypertension can lead to cardiovascular complications 2
• Focusing solely on BP numbers: Treatment should target symptom improvement rather than normalizing BP 4
• Overlooking non-pharmacological measures: These should always be implemented alongside pharmacological treatment 4
• Ignoring potential drug interactions: Be aware of potential interactions, particularly with carbidopa in Parkinson's disease patients 1, 7