What are the recommendations for managing a patient with Multiple System Atrophy who is taking domperidone?

Management of Domperidone in Multiple System Atrophy

Domperidone should be used with extreme caution in patients with Multiple System Atrophy (MSA) due to significant cardiac risks, particularly QT prolongation and increased risk of sudden cardiac death. 1, 2, 3

Cardiac Risk Assessment and Monitoring

• Domperidone has been associated with nearly fourfold increased risk of sudden cardiac death, with a safety ratio of only 5.25 (far below the minimum safety ratio of 30) 1
• ECG monitoring is essential before initiating domperidone and during treatment in MSA patients due to the increased risk of QT prolongation 4
• The risk of cardiac complications increases significantly at doses above 30 mg per day 2
• Five population-based studies show that oral domperidone significantly increases the odds ratio for sudden cardiac death to 2.8 (1.53-6.21) 3

Dosing Recommendations for MSA Patients

• If domperidone must be used, start at the lowest effective dose of 10 mg three times daily 4
• Never exceed 30 mg per day in MSA patients due to sharply increased cardiac risk at higher doses 2
• Consider dose reduction in patients with renal impairment, which is common in advanced MSA 5
• Avoid concomitant use with other QT-prolonging medications 4

Alternative Treatments for Gastroparesis in MSA

• Consider prokinetic agents with better safety profiles as first-line options 5
• 5-HT3 receptor antagonists like ondansetron (4-8 mg twice or three times daily) may be safer alternatives 5, 4
• Phenothiazine antipsychotics such as prochlorperazine (5-10 mg four times daily) can be considered, though they may worsen parkinsonian symptoms 5
• Non-pharmacological approaches including dietary modifications and smaller, more frequent meals should be implemented 5

Management of Orthostatic Hypotension in MSA

• Domperidone may worsen orthostatic hypotension, which is a cardinal feature of MSA 6, 7
• Physical counter-pressure maneuvers can be beneficial in MSA patients with neurogenic orthostatic hypotension 5
• Compression garments (at least thigh-high and preferably including the abdomen) can improve orthostatic symptoms 5
• Midodrine or droxidopa may be beneficial for managing neurogenic orthostatic hypotension in MSA patients 5

Special Considerations in MSA

• MSA is characterized by poor levodopa-responsive parkinsonism, cerebellar ataxia, pyramidal signs, and autonomic failure 6, 7
• The mean survival of MSA patients is approximately 9 years from symptom onset, making quality of life considerations paramount 6
• Autonomic and urogenital features should be identified and treated early, as they can significantly impact quality of life 6
• Current therapeutic strategies for MSA are primarily based on dopamine replacement and improvement of autonomic failure 7

Monitoring and Follow-up

• Regular ECG monitoring is essential for MSA patients on domperidone to assess for QT prolongation 4
• Monitor for signs of cardiac arrhythmias including palpitations, syncope, or pre-syncope 1, 2
• Assess effectiveness of symptom control regularly and consider alternative therapies if inadequate response 5
• Evaluate for drug interactions at each visit, particularly with other medications that may prolong QT interval 4