Recommended Treatment and Dosage for Motegrity (Prucalopride) in Adults with Chronic Idiopathic Constipation
For adults with chronic idiopathic constipation (CIC) who do not respond to over-the-counter agents, prucalopride (Motegrity) is strongly recommended at a dosage of 2 mg once daily for adults with normal renal function and 1 mg once daily for patients with severe renal impairment. 1, 2, 3
Dosing Guidelines
- The standard adult dose is 2 mg orally once daily 2, 3
- For patients with severe renal impairment (creatinine clearance <30 mL/min), the recommended dose is 1 mg once daily 2, 3
- Prucalopride can be taken with or without food 3
- No dose adjustment is needed based on age - efficacy in elderly patients (≥65 years) is comparable to the overall adult population 2, 4
Mechanism of Action and Efficacy
- Prucalopride is a selective serotonin-4 (5-HT4) receptor agonist that directly stimulates colonic motility 2, 3, 5
- It promotes peristaltic reflex, intestinal secretions, and GI motility 2
- Clinical trials demonstrate that prucalopride significantly increases complete spontaneous bowel movements (CSBMs) per week compared to placebo 1, 2
- Responder rates (≥3 CSBMs per week) are significantly higher with prucalopride compared to placebo 2
Clinical Evidence and Recommendations
- The American Gastroenterological Association and American College of Gastroenterology strongly recommend prucalopride for CIC in adults who do not respond to OTC agents (moderate certainty of evidence) 1
- Prucalopride directly stimulates colonic motility, differentiating it from other medications approved for chronic constipation 5
- Clinical trials supporting its efficacy were conducted over 4-24 weeks, though the drug label does not provide a specific treatment duration limit 1
Common Side Effects and Monitoring
- Most common adverse reactions (≥2%) include: 3
- Headache (19% vs 9% placebo)
- Abdominal pain (16% vs 11% placebo)
- Nausea (14% vs 7% placebo)
- Diarrhea (13% vs 5% placebo)
- Side effects typically occur during the first week of treatment and resolve within a few days 2, 3
- Of patients reporting diarrhea, 70% experienced it in the first week of treatment, with resolution within a few days in 73% of those patients 3
- Of patients reporting headache, 66% experienced onset in the first 2 days of treatment, with resolution within a few days in 65% of those patients 3
Important Safety Considerations
- Monitor patients for unusual changes in mood, behavior, or suicidal ideation 3
- Instruct patients to discontinue prucalopride immediately and contact their healthcare provider if they experience any unusual changes in mood or behavior 3
- Unlike some older 5-HT4 agonists, prucalopride has not shown significant cardiovascular safety issues in clinical trials 2, 3
Contraindications
- Hypersensitivity to prucalopride (reactions may include dyspnea, rash, pruritus, urticaria, and facial edema) 3
- Intestinal perforation or obstruction due to structural or functional disorder of the gut wall 3
- Obstructive ileus, severe inflammatory conditions of the intestinal tract such as Crohn's disease, ulcerative colitis, and toxic megacolon/megarectum 3
Treatment Algorithm
- Begin with 2 mg once daily (1 mg for severe renal impairment) 2, 3
- Evaluate response after 4 weeks (clinical trials showed sustained efficacy over 12 weeks) 2
- If inadequate response, consider alternative agents such as linaclotide or plecanatide, which also have strong recommendations from the AGA/ACG 1, 6
- Prucalopride can be used as a replacement for or as an adjunct to OTC agents 1
Clinical Pearls
- Warn patients about potential initial side effects (headache, nausea, diarrhea) that typically resolve within days 2, 3
- The 4 mg dose has been studied but offers no additional benefit over the 2 mg dose for most patients 2, 7
- Prucalopride may be particularly useful in patients who have failed other treatments for CIC 8
- The major drawback of prucalopride is its high cost, which may limit accessibility for some patients 8