How does Droxidopa help in treating Neurogenic Orthostatic Hypotension (NOH)?

How Droxidopa Helps in Treating Neurogenic Orthostatic Hypotension

Droxidopa improves symptoms of neurogenic orthostatic hypotension (nOH) by functioning as a synthetic precursor of norepinephrine, directly addressing the pathophysiological deficiency of norepinephrine that causes inadequate vasoconstriction upon standing. 1

Mechanism of Action

Droxidopa works through a straightforward pharmacological pathway:

1. After oral administration, droxidopa is absorbed and converted to norepinephrine
2. This conversion increases circulating norepinephrine levels
3. The increased norepinephrine compensates for the autonomic failure that characterizes nOH
4. This leads to improved vasoconstriction when standing, helping maintain blood pressure

Clinical Benefits

Droxidopa provides several important clinical benefits for patients with nOH:

• Symptom improvement: Significantly reduces dizziness, lightheadedness, and the "feeling of about to black out" that characterizes nOH 1, 2
• Blood pressure stabilization: Increases standing systolic blood pressure, with studies showing an average increase of 6.4 mmHg versus 0.7 mmHg for placebo 3
• Functional improvement: Enhances patients' ability to perform activities requiring standing for both short and long periods 4
• Fall reduction: May reduce falls in patients with nOH, according to small studies 1

FDA-Approved Indications

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 caused by:

• Primary autonomic failure (Parkinson's disease, multiple system atrophy, pure autonomic failure)
• Dopamine beta-hydroxylase deficiency
• Non-diabetic autonomic neuropathy 2

Dosing Considerations

The optimal dosing strategy for droxidopa is:

• Starting dose: 100 mg three times daily
• Timing: Upon waking, at midday, and late afternoon (at least 3 hours before bedtime)
• Titration: Increase by 100 mg three times daily every 24-48 hours
• Maximum dose: 600 mg three times daily (1,800 mg total daily dose)
• Administration: Can be taken with or without food, but consistency is important 2

Important Monitoring and Precautions

Several key precautions must be observed when using droxidopa:

• Supine hypertension: Monitor blood pressure in supine position before and during treatment, as droxidopa may cause or worsen supine hypertension 2
• Head elevation: Patients should elevate the head of the bed when resting or sleeping to reduce the risk of supine hypertension 2
• Cardiovascular risk: Poorly managed supine hypertension may increase risk of cardiovascular events, particularly stroke 2
• Drug interactions: Use of carbidopa in patients with Parkinson's disease may decrease droxidopa's effectiveness 1

Duration of Effect and Follow-up

• The FDA approval notes that effectiveness beyond 2 weeks has not been established in the original trials 2
• However, more recent research shows significant improvement from baseline in nOH symptoms and activities of daily living during 12 weeks of open-label treatment 5
• Regular assessment of continued effectiveness is recommended 2

Comparison to Other nOH Treatments

Several other treatments are available for nOH, but droxidopa has specific advantages:

• Midodrine: Also effective for nOH but works as a direct alpha-1 agonist rather than addressing the underlying norepinephrine deficiency 1, 6
• Fludrocortisone: Increases plasma volume but may cause more significant supine hypertension 1, 6
• Non-pharmacological approaches: Physical counter-pressure maneuvers, compression garments, and increased salt/fluid intake should be considered as complementary approaches 1, 6

Common Side Effects

The most common adverse events with droxidopa include:

• Headache (13.5% vs. 7.3% for placebo)
• Dizziness (10.1% vs. 4.9% for placebo)
• Supine hypertension (≤7.9% vs. ≤4.6% for placebo) 3, 7

In conclusion, droxidopa provides a targeted approach to treating nOH by addressing the underlying norepinephrine deficiency, improving orthostatic symptoms and standing blood pressure, with careful monitoring required for supine hypertension.