What is the recommended approach for using Northera (droxidopa) in patients with End-Stage Renal Disease (ESRD) experiencing neurogenic orthostatic hypotension (NOH)?

Droxidopa (Northera) in ESRD Patients with Neurogenic Orthostatic Hypotension

Droxidopa can be beneficial in ESRD patients with neurogenic orthostatic hypotension, but requires careful monitoring of blood pressure and potential dose adjustment based on dialysis schedule. 1

Mechanism and Efficacy in ESRD

Droxidopa is a synthetic amino acid that is converted to norepinephrine by the enzyme L-aromatic amino acid decarboxylase. This conversion occurs outside the central nervous system in both neural and non-neural tissues, making it effective for treating neurogenic orthostatic hypotension (NOH) in patients with both central and peripheral autonomic disorders 2.

In ESRD patients specifically:

• Research has shown that droxidopa may help reduce intradialytic hypotension complications in ESRD patients on chronic hemodialysis 3
• Treatment with 400-600mg droxidopa before dialysis demonstrated improvements in post-dialysis systolic blood pressure and reduced the frequency of hemodialysis terminations due to hypotension 3

Dosing Recommendations for ESRD

• Starting dose: Begin with 100mg three times daily
• Titration: Gradually increase by 100mg increments every 24-48 hours
• Maximum dose: Up to 600mg three times daily
• Timing: Administer approximately 1 hour before dialysis sessions and at regular intervals during non-dialysis days
• Administration: The last daily dose should be taken at least 3 hours before bedtime to reduce the risk of supine hypertension

Monitoring Parameters

• Blood pressure: Monitor supine and standing blood pressure before and after dialysis sessions
• Symptoms: Assess improvement in orthostatic symptoms using standardized tools like the Orthostatic Hypotension Questionnaire
• Adverse effects: Watch for headache, dizziness, and supine hypertension
• Efficacy duration: Be aware that efficacy may decrease gradually after 2 weeks of treatment 4

Comprehensive Management Approach

1. Non-pharmacological measures (implement first):

   • Ensure adequate salt intake unless contraindicated
   • Encourage physical activity to avoid deconditioning
   • Utilize compression garments (thigh-high or abdominal)
   • Teach counter-pressure maneuvers (leg crossing, muscle tensing)
   • Consider acute water ingestion (≥240 mL) for temporary relief 1

2. Pharmacological therapy:

   • First-line options: Midodrine or droxidopa 1
   • Second-line options: Fludrocortisone (use with caution in ESRD)
   • Third-line options: Pyridostigmine or octreotide for refractory cases 1

Important Considerations for ESRD Patients

• Fluid management: Balance the need for volume repletion with fluid restrictions in ESRD
• Medication timing: Coordinate droxidopa administration with dialysis schedule
• Blood pressure monitoring: Pay special attention to supine hypertension risk
• Duration of therapy: Be aware that evidence for long-term efficacy beyond 12 weeks is limited 5

Potential Pitfalls and Caveats

• Supine hypertension: Monitor for this common side effect, especially in ESRD patients who may already have hypertension
• Efficacy duration: The benefit of droxidopa may decrease over time, with studies showing reduced efficacy after 8 weeks 4
• Concomitant medications: Avoid carbidopa in patients with Parkinson's disease as it may decrease droxidopa effectiveness 1
• Symptom focus: Evaluate treatment effectiveness based on symptom improvement rather than blood pressure normalization 6

Droxidopa has been shown to be well-tolerated in ESRD patients, with common side effects including falls, headache, and dizziness 5, 3. The medication offers a viable option for managing NOH in this challenging population when used as part of a comprehensive treatment approach.