Droxidopa for Neurogenic Orthostatic Hypotension: Treatment and Dosing
Droxidopa is indicated for the treatment of neurogenic orthostatic hypotension (nOH) with a recommended starting dose of 100 mg three times daily, titrated up to a maximum of 600 mg three times daily based on symptomatic response. 1
Indication and Patient Selection
Droxidopa is specifically approved for:
- Treatment of orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adult patients with symptomatic nOH
- Appropriate for nOH caused by:
- Primary autonomic failure (Parkinson's disease, multiple system atrophy, pure autonomic failure)
- Dopamine beta-hydroxylase deficiency
- Non-diabetic autonomic neuropathy
Dosing Protocol
Initial Dosing and Titration
- Starting dose: 100 mg orally three times daily 1
- Timing: Upon arising in the morning, at midday, and in late afternoon (at least 3 hours before bedtime) 1
- Titration: Increase by 100 mg three times daily every 24-48 hours 1
- Maximum dose: 600 mg three times daily (1,800 mg total daily dose) 1
- Administration: Take consistently either with or without food; swallow capsules whole 1
Monitoring During Treatment
- Monitor supine blood pressure prior to initiating treatment and after each dose increase 1
- Evaluate continued effectiveness periodically (effectiveness beyond 2 weeks has not been established in clinical trials) 1
- Monitor for supine hypertension, which may occur or worsen with treatment 1
Efficacy and Clinical Outcomes
Droxidopa has demonstrated significant improvements in:
- Orthostatic Hypotension Symptom Assessment (OHSA) scores 2, 3
- Dizziness/lightheadedness symptoms 3, 4
- Activities of daily living that require standing 5
- Standing systolic blood pressure (average increase of 11.5 mmHg compared to 4.8 mmHg with placebo) 3
A 12-week open-label study showed sustained benefits with significant improvements in symptoms and activities of daily living throughout the treatment period 2.
Important Precautions
Supine Hypertension
- Critical warning: Droxidopa may cause or worsen supine hypertension 1
- Management: Elevate the head of the bed when resting or sleeping 1
- Monitoring: Regularly check blood pressure in both supine and head-elevated positions 1
- Action: Reduce or discontinue droxidopa if supine hypertension persists 1
Other Precautions
- May exacerbate existing ischemic heart disease, arrhythmias, and congestive heart failure 1
- Risk of hyperpyrexia and confusion resembling neuroleptic malignant syndrome, especially when changing dosage or discontinuing concomitant levodopa 1
- Use with caution in patients taking DOPA decarboxylase inhibitors, as dose adjustments may be required 1
Contraindications
- History of hypersensitivity to droxidopa or its ingredients 1
Common Adverse Effects
Alternative Treatments for nOH
If droxidopa is not suitable or ineffective, consider:
- Midodrine (2.5-10 mg three times daily) 6
- Fludrocortisone (0.1-0.3 mg daily) 6, 7
- Pyridostigmine (30-60 mg 2-3 times daily) 6
Clinical Pearls
- The last dose should be taken at least 3 hours before bedtime to minimize risk of supine hypertension 1
- Droxidopa may be more effective in patients not using dopa decarboxylase inhibitors 3
- Long-term safety studies show droxidopa is generally well-tolerated with continued use 8
- Non-pharmacological measures should be implemented alongside medication, including compression garments, increased salt and fluid intake (if not contraindicated), and physical counter-pressure maneuvers 6, 7
Droxidopa offers significant benefits for patients with nOH, but careful monitoring for supine hypertension is essential throughout treatment.