What is the comparison between Motegrity (prucalopride) and Linzess (linaclotide) for treating chronic idiopathic constipation?

Comparison of Motegrity (prucalopride) vs. Linzess (linaclotide) for Chronic Idiopathic Constipation

For chronic idiopathic constipation, Linzess (linaclotide) is recommended over Motegrity (prucalopride) due to its stronger evidence base, higher certainty of efficacy, and well-documented effects on both constipation and abdominal symptoms. 1, 2

Mechanism of Action

• Linaclotide (Linzess): Guanylate cyclase-C agonist that increases cyclic guanosine monophosphate concentrations, resulting in luminal chloride and bicarbonate secretion, increasing intestinal fluid and accelerating GI transit 1

• Prucalopride (Motegrity): 5-HT4 receptor agonist (prokinetic agent) with greater receptor selectivity than previous drugs in this class 1, 3

Efficacy

Linaclotide (Linzess)

• Strong recommendation from the American Gastroenterological Association (AGA) with moderate certainty of evidence 1
• Significantly increases complete spontaneous bowel movements (CSBMs) per week (MD 1.37,95% CI 1.07–1.95) 1
• Increases spontaneous bowel movements (SBMs) per week (MD 1.97,95% CI 1.59–2.36) 1
• Improves stool consistency (MD 1.25,95% CI 1.1–1.39 higher) 1
• Increases global relief rates (RR 1.96,95% CI 1.63–2.35) 1
• Particularly effective for patients with abdominal bloating and discomfort 4

Prucalopride (Motegrity)

• May have additional benefit for abdominal pain 1
• Less robust evidence base compared to linaclotide 1, 3

Dosing

Linaclotide (Linzess)

• CIC dosing: 72μg or 145μg once daily 1, 2, 5
• Should be taken on an empty stomach, 30 minutes before the first meal of the day 1
• Offers more dosing flexibility with multiple approved doses 2

Prucalopride (Motegrity)

• 1-2 mg daily 1
• Maximum dose: 2 mg daily 1

Side Effects

Linaclotide (Linzess)

• Diarrhea is the most common adverse effect (patients 3 times more likely to have diarrhea leading to discontinuation compared to placebo) 1, 2
• Discontinuation due to diarrhea: 2.4% (72μg dose) to 3.2% (145μg dose) 5

Prucalopride (Motegrity)

• Headaches and diarrhea are common side effects 1, 3
• Generally well-tolerated but may cause gastrointestinal issues 3

Cost Considerations

• Linaclotide: Approximately $523/month 1
• Prucalopride: Approximately $563/month 1

Special Populations

Renal/Hepatic Impairment

• Linaclotide: Minimal systemic absorption, no dose adjustment required 2
• Prucalopride: Caution advised in patients with impaired liver and renal function 3

Elderly Patients

• Linaclotide: Efficacy in persons 65 years and older is comparable with the overall study population 1
• Prucalopride: Less documented experience in elderly populations 2

Treatment Algorithm for CIC

1. First-line: Over-the-counter agents (fiber supplements, osmotic laxatives like polyethylene glycol)

2. Second-line (if OTC agents fail):

   • For patients with prominent abdominal bloating/discomfort: Linaclotide (start with 72μg, can increase to 145μg if needed after 4 weeks)
   • For patients with normal or minimal abdominal symptoms: Either medication is appropriate, but linaclotide has stronger evidence

3. Alternative options (if initial prescription medication fails):

   • Switch from linaclotide to prucalopride or vice versa
   • Consider other secretagogues like plecanatide or lubiprostone

Contraindications for Both Medications

• Known or suspected mechanical GI obstruction 1, 2

Key Clinical Pearls

• Diarrhea is an expected side effect for both medications and not necessarily a reason to discontinue treatment 2
• Start with lower doses of linaclotide (72μg) if diarrhea is a concern 2, 5
• Both medications work relatively quickly, with effects often seen within days 1
• Neither medication should be used in patients with mechanical obstruction 1, 2