What is the recommended treatment regimen for an adult patient with chronic idiopathic constipation using Trulance (plecanatide)?

Trulance (Plecanatide) Treatment Regimen for Chronic Idiopathic Constipation

The recommended treatment regimen for adults with chronic idiopathic constipation is plecanatide 3 mg taken orally once daily, with or without food, used as a second-line agent after inadequate response to over-the-counter laxatives. 1, 2

Dosing and Administration

• Standard dose: 3 mg orally once daily 2
• Timing: Can be taken with or without food 2
• Missed dose: Skip the missed dose and take the next dose at the regular time; do not double dose 2
• Tablet administration: Swallow whole, or may be crushed and mixed with applesauce or water for patients with swallowing difficulties 2

Clinical Positioning in Treatment Algorithm

Plecanatide receives a strong recommendation from the American Gastroenterological Association-American College of Gastroenterology as a second-line agent for adults with chronic idiopathic constipation who do not respond to over-the-counter agents. 1

• Use plecanatide after a 4-12 week trial of first-line therapy with polyethylene glycol (PEG) 17g daily has proven inadequate 3
• Can be used as a replacement for or as an adjunct to over-the-counter agents 1
• Trial duration in clinical studies was 12 weeks, though the FDA label does not specify a treatment duration limit 1, 2

Mechanism and Expected Efficacy

Plecanatide is a guanylate cyclase-C agonist that increases cyclic guanosine monophosphate concentrations, resulting in luminal chloride and bicarbonate secretion, thereby increasing intestinal fluid and accelerating gastrointestinal transit. 1

Expected clinical benefits include: 1

• Increase in complete spontaneous bowel movements (CSBMs) by 1.1 per week (95% CI 0.85-1.35)
• Increase in spontaneous bowel movements (SBMs) by 1.66 per week (95% CI 1.37-1.94)
• Improved quality-of-life scores
• Improved stool consistency (Bristol Stool Form Scale improvement: MD 0.83,95% CI 0.6-1.05)
• Responder rate of 88 more per 1,000 patients (defined as ≥3 CSBMs per week and ≥1 CSBM over baseline for ≥9 of 12 weeks)

Safety Profile and Adverse Effects

The most common adverse effect is diarrhea, occurring in approximately 5% of patients, with 3.1% discontinuing treatment due to diarrhea. 1, 4, 5

• Risk of diarrhea leading to discontinuation: 27 more per 1,000 patients compared to placebo (RR 5.39,95% CI 2.40-12.11) 1
• Most adverse events are mild to moderate in severity 4, 6
• If severe diarrhea occurs, suspend dosing and rehydrate the patient 2
• Long-term safety data up to 72 weeks shows low discontinuation rates (5.3% overall, 3.1% due to diarrhea) 5

Contraindications and Warnings

Absolute contraindications: 2

• Patients less than 6 years of age (risk of serious dehydration and death)
• Known or suspected mechanical gastrointestinal obstruction

Avoid use: 2

• Patients 6 years to less than 18 years of age
• Safety and effectiveness not established in patients under 18 years

Special Populations

• Elderly patients (≥65 years): No clear differences in outcomes observed in clinical trials, though sample sizes were too small for formal age-related analysis 1
• Severe constipation: Plecanatide remains effective in patients with severe constipation (no CSBMs at baseline with severe straining), with response rates of 20.9% for 3 mg versus 11.3% for placebo 7

Clinical Pitfalls to Avoid

• Do not continue escalating over-the-counter laxative doses indefinitely—switch to plecanatide after 4-12 weeks of inadequate response to PEG 3
• Do not use in pediatric patients—contraindicated in children under 6 years due to risk of fatal dehydration 2
• Rule out mechanical obstruction before initiating therapy, particularly if imaging shows prominent fecal loading 3
• Monitor for diarrhea, especially in the first few weeks of treatment, and adjust therapy accordingly 1, 2

Patient Satisfaction and Long-Term Use

Long-term studies demonstrate high patient satisfaction (median score 4.0 = "quite satisfied") and desire to continue treatment (median score 4.0 = "quite likely"), with most discontinuations due to loss of efficacy or insurance barriers rather than adverse events. 1, 5