When to prescribe plecanatide (guanylate cyclase-C agonist) for chronic idiopathic constipation?

When to Prescribe Plecanatide for Chronic Idiopathic Constipation

Plecanatide should be prescribed for adults with chronic idiopathic constipation (CIC) who do not respond to over-the-counter (OTC) agents. 1

Mechanism of Action and Indications

Plecanatide is a pH-dependent guanylate cyclase-C (GC-C) agonist that:

• Increases cyclic guanosine monophosphate concentrations in intestinal epithelial cells
• Results in luminal chloride and bicarbonate secretion
• Increases intestinal fluid and accelerates gastrointestinal transit 1

The FDA has approved plecanatide for:

• Treatment of chronic idiopathic constipation (CIC) in adults at a dose of 3 mg daily
• Treatment of irritable bowel syndrome with constipation (IBS-C) in adults at the same dose 2

Evidence-Based Prescription Algorithm

Step 1: Confirm Diagnosis of CIC

• Ensure patient meets modified Rome III criteria for CIC (< 3 complete spontaneous bowel movements per week and infrequent loose stools without laxative use) 3
• Rule out secondary causes of constipation

Step 2: First-Line Therapy

• Start with OTC agents:
  • Fiber supplements
  • Osmotic laxatives (e.g., polyethylene glycol)
  • Stool softeners 1

Step 3: Second-Line Therapy (When to Prescribe Plecanatide)

• Prescribe plecanatide 3 mg daily when:
  • Patient has inadequate response to OTC agents
  • Patient continues to experience symptoms of CIC despite first-line therapy 1

Efficacy of Plecanatide

Plecanatide has demonstrated significant efficacy in clinical trials:

• Increases complete spontaneous bowel movements (CSBMs) per week by 1.1 (95% CI 0.85-1.35)
• Increases spontaneous bowel movements (SBMs) per week by 1.66 (95% CI 1.37-1.94)
• Improves stool consistency based on Bristol Stool Form Scale (MD 0.83,95% CI 0.6-1.05)
• Increases responder rates (RR 1.78,95% CI 1.46-2.18) 1

In phase III trials, plecanatide demonstrated:

• Significantly greater percentage of durable overall CSBM responders compared to placebo (20.1% vs 12.8%, p=0.004)
• Improvements in stool consistency and frequency beginning in week 1 and maintained through week 12 4

Safety Considerations

Adverse Effects

• Diarrhea is the most common adverse event:
  • Occurs in approximately 3-5% of patients
  • May lead to treatment discontinuation in about 1-3% of patients 4, 1
• The risk of diarrhea leading to discontinuation is higher with plecanatide compared to placebo (RR 5.39,95% CI 2.40-12.11) 1

Contraindications

• Contraindicated in patients less than 6 years of age due to risk of serious dehydration
• Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 2

Special Populations

Elderly Patients

• Plecanatide is effective and well-tolerated in patients ≥65 years
• No clear differences in outcomes among individuals older than 65 years in clinical trials
• No dose adjustment required based on age 1, 5

Implementation Considerations

• Can be used as a replacement for or as an adjunct to OTC agents
• Taken with or without food at a dose of 3 mg daily
• No limit on duration of treatment in the drug label, though clinical trials were 12 weeks 1, 2
• Monitor for diarrhea, especially in the first week of treatment 6

Comparison with Other Prescription Options

When choosing between prescription medications for CIC:

• Plecanatide and linaclotide (another GC-C agonist) have similar efficacy profiles
• Plecanatide may have a lower incidence of diarrhea compared to linaclotide
• Prucalopride (a 5-HT4 agonist) is another strong recommendation for CIC patients who don't respond to OTC agents 1

Pitfalls and Caveats

• Patients should be warned about the potential for diarrhea, especially in the first week of treatment
• Ensure adequate hydration, particularly in elderly patients
• Most adverse events related to plecanatide occur within the first 7 days of treatment 6
• Insurance coverage may be a barrier; prior authorization may be required

By following this evidence-based approach, plecanatide can be effectively prescribed to appropriate patients with chronic idiopathic constipation who have not responded adequately to over-the-counter treatments.