MOTEGRITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MOTEGRITY (MOTEGRITY).
Prucalopride is a selective, high-affinity serotonin 5-HT4 receptor agonist that stimulates colonic motility by enhancing peristalsis and accelerating gastrointestinal transit.
| Metabolism | Minimal hepatic metabolism; primarily excreted unchanged in urine (60-70%) and feces; main metabolite is N-dealkylated product via CYP3A4 (minor pathway). |
| Excretion | Primarily hepatobiliary and fecal elimination; approximately 85% of absorbed dose recovered in feces (mostly as metabolites) and <4% in urine as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 8 hours in healthy subjects, supporting twice-daily dosing. |
| Protein binding | Approximately 87% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is about 130 L (approximately 1.8 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 20% due to first-pass metabolism. |
| Onset of Action | Oral: Onset of clinical effect (improved bowel movements) observed within 24 hours of first dose, with maximal effect reached by 2 weeks. |
| Duration of Action | Duration of action supports twice-daily administration; sustained improvement in bowel function with chronic dosing. |
2 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min; not recommended in end-stage renal disease (GFR <15 mL/min). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B and C: not recommended due to increased exposure. |
| Pediatric use | Safety and efficacy not established in pediatric patients younger than 18 years. |
| Geriatric use | No dose adjustment required; monitor for adverse effects such as diarrhea due to potential increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MOTEGRITY (MOTEGRITY).
| Breastfeeding | Prucalopride is excreted in human breast milk. A study of 12 lactating women receiving a single 2 mg dose estimated the mean milk-to-plasma ratio (M/P) as 2.44. The estimated daily infant dose via milk is approximately 1.1-1.5% of the maternal weight-adjusted dose. Caution is advised; consider the developmental and health benefits of breastfeeding along with the mother's clinical need. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, administration of prucalopride to pregnant rats and rabbits during organogenesis at doses up to 47 and 12 times the maximum recommended human dose (MRHD) of 2 mg/day (based on AUC) resulted in increased post-implantation loss and reduced fetal body weight in rats, but no evidence of teratogenicity. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to prucalopride or any component","Renal impairment with creatinine clearance <30 mL/min","Intestinal perforation or obstruction due to structural or functional disorder of the gut wall","Obstructive ileus","Severe inflammatory conditions of the intestinal tract (e.g., Crohn's disease, ulcerative colitis, toxic megacolon)"]
| Precautions | ["Hypersensitivity reactions (angioedema, urticaria) have been reported","Risk of severe diarrhea requiring dose reduction or discontinuation","Volume depletion and electrolyte imbalance may occur with severe diarrhea","Use with caution in patients with renal impairment (CrCl <30 mL/min: contraindicated)","Avoid use in patients with known hypersensitivity to prucalopride"] |
Loading safety data…
| Fetal Monitoring | No specific monitoring required, but observe for potential adverse effects if used during pregnancy. Monitor for electrolyte imbalance as prucalopride may cause diarrhea, leading to dehydration and electrolyte disturbances, especially in pregnant women with hyperemesis or restricted fluid intake. |
| Fertility Effects | In animal studies, prucalopride did not affect fertility in male or female rats at doses up to 47 times the MRHD. No human data available; clinically relevant effects on fertility are unlikely. |