prucalopride
Brand: Motegrity
Prototype Drug
Drug Class: selective serotonin type-4 (5-HT4) receptor agonist
Drug Family: GI agent
Subclass: prokinetic agent
Organ Systems: gastrointestinal
Mechanism of Action
Highly selective 5-HT4 receptor agonist in the enteric nervous system. Activating 5-HT4 receptors on cholinergic neurons in the myenteric plexus stimulates release of acetylcholine, which enhances peristaltic contractions throughout the colon, accelerating colonic transit.
5-HT4 receptors (enteric nervous system)
Indications
- chronic idiopathic constipation (adults)
Contraindications
- intestinal obstruction or perforation
- severe hepatic impairment
- dialysis patients
Adverse Effects
Common
- headache (22%)
- nausea
- diarrhea
- abdominal pain
- flatulence
Serious
- suicidal ideation (rare; FDA label)
- cardiovascular effects (rare)
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~90%; not affected by food |
| Distribution | Vd 567 L; widely distributed |
| Metabolism | minimal hepatic metabolism; primarily unchanged |
| Excretion | renal (~60% unchanged) |
| Half-life | 24 hours |
| Onset | days to 2 weeks |
| Peak | 2–3 hours |
| Duration | 24 hours |
| Protein Binding | 30% |
| Vd | 567 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| P-glycoprotein inhibitors (ketoconazole) | inhibit renal secretion of prucalopride, increasing exposure | moderate |
Nursing Considerations
- Prucalopride can be taken with or without food; once-daily dosing improves adherence.
- Monitor for suicidal ideation or mood changes per the FDA label; assess patient mental health history before initiation.
- Dose adjustment recommended in severe renal impairment (eGFR <30 mL/min): use 1 mg daily instead of 2 mg.
- Advise patients that headache is common in the first few days but typically resolves with continued use.
Clinical Pearls
- Unlike metoclopramide, prucalopride's high selectivity for 5-HT4 receptors over dopamine receptors eliminates the risk of extrapyramidal side effects and QT prolongation, making it significantly safer for long-term use.
- Unlike cisapride (withdrawn for QT prolongation), prucalopride does not affect hERG channels, giving it a clean cardiac safety profile.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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