Motegrity (Prucalopride) and Central Sleep Apnea

There is no evidence that Motegrity (prucalopride) causes central sleep apnea based on the available medical literature and guidelines.

Mechanism of Action and Safety Profile

Prucalopride (Motegrity) is a selective serotonin 5-HT4 receptor agonist with colonic prokinetic activity, used primarily for chronic idiopathic constipation 1, 2
Unlike earlier 5-HT4 receptor agonists (cisapride and tegaserod), prucalopride does not interact with cardiac hERG potassium channels or other serotonergic receptors in blood vessels, which contributes to its favorable cardiovascular safety profile 1, 3
The most common adverse events reported with prucalopride are headache, nausea, abdominal pain, and diarrhea, primarily occurring on the first day of treatment 2

Central sleep apnea is characterized by a temporary cessation of breathing during sleep due to a lack of respiratory effort, which is different from obstructive sleep apnea 4
Known medications that can cause or worsen central sleep apnea include:
- Benzodiazepines, which should be avoided in patients with sleep apnea as they can depress upper airway tone and worsen sleep-disordered breathing 5
- Opioids, which increase the risk of sleep apnea by affecting respiratory drive 4
Medications that have been studied for their effects on central sleep apnea include:
- Acetazolamide and theophylline, which can reduce central sleep apnea events but may lead to increased cardiac arrhythmias 4
- Protriptyline and other tricyclic antidepressants, which have been studied for obstructive sleep apnea but have not shown significant impact on respiratory indices 4

In clinical trials of prucalopride, no cardiovascular safety issues were identified 2, 6
The incidence of QT interval prolongation with prucalopride at therapeutic doses (2 and 4 mg/day) was low and similar to placebo 6
Even at doses up to 20 mg/day (10 times the recommended therapeutic dose), prucalopride had no clinically relevant effects on cardiovascular parameters in healthy volunteers 6
The American Gastroenterological Association (AGA) notes that the most common adverse events with prucalopride are abdominal pain and nausea, with no mention of respiratory depression or sleep apnea 4

When evaluating patients with central sleep apnea, clinicians should focus on common causes such as heart failure, neurological disorders, atrial fibrillation, pulmonary hypertension, and renal failure 5
For patients requiring treatment for chronic constipation who also have sleep apnea, prucalopride appears to be a safe option based on current evidence 1, 2
Patients with risk factors for central sleep apnea (e.g., heart failure, opioid use) should be monitored for symptoms of sleep-disordered breathing regardless of prucalopride use 4, 5

The available evidence does not suggest that prucalopride causes central sleep apnea 1, 2, 6
When treating patients with both chronic constipation and sleep disorders, prucalopride may be considered a safer option compared to medications with known respiratory depressant effects 1, 3