What is the recommended treatment and dosage for Trulance (plecanatide) in adults with chronic idiopathic constipation?

Trulance (Plecanatide) for Chronic Idiopathic Constipation

For adults with chronic idiopathic constipation who have not responded to over-the-counter agents, use plecanatide 3 mg orally once daily, taken with or without food. 1

Dosing and Administration

• The FDA-approved dose is 3 mg once daily for both chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) 1
• Take with or without food—food does not affect efficacy 1
• Swallow tablets whole; if swallowing difficulties exist, tablets can be crushed and mixed with applesauce or water, or administered via nasogastric/gastric feeding tube 1
• If a dose is missed, skip it and resume at the regular time—do not double dose 1

Evidence Supporting Use

The 2023 AGA-ACG guidelines provide a strong recommendation for plecanatide in adults with CIC who do not respond to OTC agents, with moderate certainty of evidence. 2

Efficacy Outcomes

• Plecanatide increases complete spontaneous bowel movements (CSBMs) by 1.1 per week (95% CI 0.85-1.35) and spontaneous bowel movements (SBMs) by 1.66 per week (95% CI 1.37-1.94) compared to placebo 2
• Durable responder rates (≥3 CSBMs/week plus ≥1 CSBM increase from baseline for ≥9 of 12 weeks) were significantly higher: 20-21% with plecanatide versus 10-13% with placebo 2, 3
• Improves stool consistency on Bristol Stool Form Scale (MD 0.83,95% CI 0.6-1.05) 2
• Significantly improves quality of life scores with high certainty of evidence 2
• Benefits begin in week 1 and are maintained through 12 weeks 3

Mechanism of Action

• Plecanatide is a pH-dependent guanylate cyclase-C agonist that increases cyclic guanosine monophosphate, resulting in luminal chloride and bicarbonate secretion 2
• This increases intestinal fluid and accelerates gastrointestinal transit 2
• The pH-dependent mechanism limits systemic absorption and diarrhea risk 4

Safety Profile and Adverse Effects

Diarrhea is the primary adverse effect but occurs infrequently:

• Diarrhea leading to treatment discontinuation occurs in approximately 27 more per 1,000 patients compared to placebo (RR 5.39,95% CI 2.40-12.11), but the absolute risk remains small 2
• Overall diarrhea rates: 3.2-5% with plecanatide versus 1.3% with placebo 4, 3
• Most adverse events are mild to moderate 3
• Serious adverse events are rare (0.8%) and similar to placebo rates 5
• Hyponatremia has not been identified as an adverse effect in clinical trials 5

Critical Safety Warnings

• CONTRAINDICATED in patients less than 6 years of age due to risk of fatal dehydration 1
• Avoid use in patients 6 to less than 18 years of age 1
• Contraindicated in known or suspected mechanical gastrointestinal obstruction 1
• If severe diarrhea occurs, suspend dosing and rehydrate the patient 1

Clinical Implementation

Use plecanatide as either a replacement for or adjunct to OTC agents in patients with inadequate response. 2

• Trial duration in studies was 12 weeks, but the FDA label does not provide a treatment duration limit 2
• No dose adjustment needed for patients over 65 years, though sample sizes were limited for formal age-related analysis 2
• May provide concurrent abdominal pain relief based on indirect evidence from IBS-C trials 2
• Effective even in patients with severe constipation (no CSBMs at baseline with severe straining) 6

Common Pitfalls to Avoid

• Do not use in pediatric patients—this carries a boxed warning for fatal dehydration risk 1
• Do not increase the dose beyond 3 mg daily—the 6 mg dose showed no additional benefit over 3 mg 3
• Monitor patients who develop severe diarrhea for dehydration and electrolyte imbalances as standard precaution 5
• Ensure no mechanical obstruction before initiating therapy 1