What is DROXIDOPA (Northera)?

Droxidopa (Northera): A Medication for Neurogenic Orthostatic Hypotension

Droxidopa is an FDA-approved synthetic amino acid precursor of norepinephrine used primarily for treating symptomatic neurogenic orthostatic hypotension (nOH) in patients with autonomic failure, including those with Parkinson's disease, multiple system atrophy, and pure autonomic failure. 1, 2

Mechanism of Action

Droxidopa works through a specific pathway:

• It is a synthetic amino acid analog directly metabolized to norepinephrine by dopa-decarboxylase, which is extensively distributed throughout the body 2
• Exerts its pharmacological effects through norepinephrine, not through the parent molecule or other metabolites 2
• Norepinephrine increases blood pressure by inducing peripheral arterial and venous vasoconstriction 2
• This helps counteract the drop in blood pressure that occurs when standing in patients with nOH 1

Clinical Use and Efficacy

Droxidopa is specifically indicated for:

• Symptomatic neurogenic orthostatic hypotension due to:
  • Parkinson's disease
  • Multiple system atrophy
  • Pure autonomic failure
  • Non-diabetic autonomic neuropathy 1

Evidence shows that droxidopa:

• Improves symptoms of neurogenic OH 1
• May reduce falls according to small studies 1
• Demonstrates significant improvement in activities requiring standing for short and long periods 3
• Shows most benefit in the first 2 weeks of treatment, with efficacy potentially decreasing over time 4

Dosing and Administration

• Available in capsule form (100 mg, 200 mg, 300 mg)
• Typical dosing range: 100-600 mg three times daily 5
• Peak plasma concentrations reached within 1-4 hours (mean ~2 hours) 2
• High-fat meals may delay absorption by approximately 2 hours 2
• Elimination half-life is approximately 2.5 hours 2

Precautions and Monitoring

Key precautions when using droxidopa:

• Supine hypertension: A major limiting factor that requires careful monitoring 1
• Renal impairment: Droxidopa and its metabolites are primarily cleared renally; limited clinical experience in severe renal impairment (GFR <30 mL/min) 2
• Carbidopa interaction: In patients with Parkinson's disease, carbidopa may decrease the effectiveness of droxidopa 1
• Pregnancy and lactation: Limited data available; droxidopa is present in rat milk and may affect nursing infants 2

Common Side Effects

Common adverse effects include:

• Headache
• Dizziness
• Nausea
• Supine hypertension 1, 5

Practical Management Considerations

When using droxidopa for nOH:

1. Start with non-pharmacological measures first:

   • Increased salt and fluid intake
   • Physical counter-pressure maneuvers
   • Compression garments
   • Avoiding prolonged standing 1, 6

2. Consider droxidopa when:

   • Non-pharmacological measures are insufficient
   • Patient has symptomatic nOH affecting quality of life
   • Other medications (midodrine, fludrocortisone) have been ineffective or poorly tolerated 1, 6

3. Monitor for:

   • Supine hypertension (measure blood pressure when lying down)
   • Symptom improvement rather than blood pressure normalization 6
   • Falls and fall-related injuries 7

Important Clinical Pearls

• The therapeutic goal is to minimize postural symptoms rather than to restore normotension 1
• Droxidopa might be particularly beneficial in reducing falls in patients with nOH 7
• Efficacy may decrease after 2 weeks of treatment, with statistical significance lost after 8 weeks in some studies 4
• Consider combination therapy with other agents for severe cases 6
• Avoid using in patients with severe uncontrolled supine hypertension 1

Droxidopa represents an important treatment option for patients with symptomatic neurogenic orthostatic hypotension, particularly when other treatments have failed or are contraindicated.