Can concomitant use of nortriptyline (tricyclic antidepressant) and domperidone (peripheral dopamine receptor antagonist) increase the risk of QT interval prolongation in a 67-year-old patient with signs of pharyngeal and oesophageal dysmotility?

QT Prolongation Risk with Nortriptyline and Domperidone Combination

Both nortriptyline and domperidone can cause QT interval prolongation, and their concurrent use creates a significant risk of QT prolongation that could lead to potentially fatal arrhythmias in your 67-year-old patient. You should avoid this combination and consider alternative treatments for the patient's pharyngeal and esophageal dysmotility.

Risk Assessment

Individual Drug Risks

1. Nortriptyline (Tricyclic Antidepressant)

   • Tricyclic antidepressants are known to prolong the QT interval 1
   • Classified as a medication with risk of QT prolongation
   • Risk increases with higher doses (patient is on 75mg)

2. Domperidone (Peripheral Dopamine Receptor Antagonist)

   • Specifically identified in guidelines as causing QT prolongation 1
   • National Patient Safety Agency alerts have been issued highlighting problems with prolonged QTc 1
   • Requires QTc monitoring for long-term use 1

Combined Risk Factors

The risk is substantially increased due to:

• Age: 67 years old (increased risk, especially in females)
• Polypharmacy: Combination of two QT-prolonging medications
• Specific drug interaction: Domperidone and tricyclic antidepressants are specifically mentioned as having risk of prolonged QT interval 1

Monitoring Recommendations (If Combination Cannot Be Avoided)

If for some reason this combination must be used (which is not recommended):

1. Baseline ECG before starting domperidone
2. Follow-up ECG at 7 days after initiation and following any dosing changes 1
3. Regular QTc monitoring throughout treatment
4. Electrolyte monitoring (particularly potassium and magnesium) 1
5. Discontinue treatment if:
   • QTc exceeds 500 ms
   • QTc increases by >60 ms from baseline
   • Patient develops clinically significant ventricular arrhythmia 1

Alternative Treatment Options

For Pharyngeal and Esophageal Dysmotility:

1. Prucalopride

   • 5-HT4 receptor agonist
   • Does not affect the QT interval 1
   • Lacks the cardiac risks of other prokinetics

2. Erythromycin/Azithromycin

   • Motilin agonist properties
   • Azithromycin may be more effective for small bowel dysmotility 1
   • Consider short-term use to avoid tachyphylaxis
   • Monitor for QT effects but generally safer than domperidone in this context

3. Octreotide

   • Somatostatin analogue
   • May be beneficial especially when other treatments have failed
   • Can improve motility and reduce symptoms 1
   • Administered subcutaneously (50-100 μg once or twice daily)

4. Pyridostigmine

   • Parasympathomimetic that enhances intestinal motility
   • Has shown benefit for refractory conditions
   • Use a stepped dosing regimen to improve tolerability 1

Management Algorithm

1. Discontinue planned domperidone due to high risk with concurrent nortriptyline

2. Consider if nortriptyline is essential:

   • If not essential: Switch to non-QT prolonging antidepressant
   • If essential: Select alternative prokinetic from options above

3. First-line alternative: Prucalopride (lacks QT effects)

4. Second-line alternatives:

   • Erythromycin/Azithromycin (short course)
   • Octreotide (for refractory cases)

5. If prokinetic therapy is absolutely necessary and no alternatives are suitable:

   • Reduce nortriptyline dose if possible
   • Start domperidone at lowest effective dose (10mg daily)
   • Implement strict ECG monitoring protocol
   • Monitor electrolytes regularly
   • Discontinue immediately if QTc prolongation occurs

Key Cautions

• The combination of multiple QT-prolonging medications significantly increases the risk of torsades de pointes 2
• Elderly patients are at higher risk for QT prolongation and subsequent arrhythmias
• Even though a recent study showed domperidone at 30-80mg daily was associated with QT prolongation in only 6% of patients 3, the combination with nortriptyline substantially increases this risk
• Avoid other QT-prolonging medications (including many common antiemetics) 1

Remember that while the risk of serious arrhythmias may be relatively low, the potential outcome (sudden cardiac death) is severe, making this a high-risk combination that should be avoided whenever possible.