When is the ideal time to prescribe plecanatide and linaclotide (guanylate cyclase-C (GC-C) agonists) for patients with Chronic Idiopathic Constipation (CIC) or Irritable Bowel Syndrome with Constipation (IBS-C)?

Ideal Timing for Plecanatide and Linaclotide Administration

Both plecanatide and linaclotide should be taken on an empty stomach, with linaclotide administered at least 30 minutes before the first meal of the day, while plecanatide can be taken with or without food. 1, 2

Administration Timing and Instructions

Linaclotide (Linzess)

• Timing: Take on an empty stomach, at least 30 minutes prior to the first meal of the day
• Consistency: Take at approximately the same time each day
• Dosage for adults:
  • IBS-C: 290 mcg once daily
  • CIC: 145 mcg once daily (72 mcg may be used based on individual tolerability)
  • Functional constipation in children 6-17 years: 72 mcg once daily 3, 2

Plecanatide (Trulance)

• Timing: Can be taken with or without food
• Dosage for adults:
  • CIC: 3 mg once daily
  • IBS-C: 3 mg once daily 1

Administration Method

• Do not crush or chew either medication
• Swallow capsules whole
• For patients who have difficulty swallowing:
  • Linaclotide: Can be opened and sprinkled on applesauce or mixed with water, or administered via nasogastric/gastrostomy tube 2

Efficacy Considerations

• Both medications are guanylate cyclase-C (GC-C) agonists with similar mechanisms of action and efficacy profiles 4
• Linaclotide is considered the most efficacious secretagogue available for IBS-C according to the British Society of Gastroenterology 1
• Both medications improve:
  • Complete spontaneous bowel movements (CSBMs)
  • Spontaneous bowel movements (SBMs)
  • Stool consistency
  • Quality of life measures 1

Adverse Effects Management

• Main side effect: Diarrhea (most common adverse event for both medications)
  • Linaclotide: Occurs in approximately 16-20% of patients 3
  • Plecanatide: May have similar rates of diarrhea but different definitions were used in clinical trials 4
• Discontinuation rates due to diarrhea:
  • Linaclotide: ~4% of patients 3, 5
  • Plecanatide: ~2.7% of patients 6
• If severe diarrhea occurs, suspend dosing and rehydrate the patient 2

Special Considerations

• Contraindications:
  • Both medications are contraindicated in patients with known or suspected mechanical GI obstruction 1, 2
  • Both are contraindicated in children less than 2 years of age 2
• Elderly patients: Use with caution as they may be more susceptible to diarrhea-induced dehydration 3

Clinical Pearls

• Morning administration is typically preferred to align with natural circadian rhythms of bowel function
• The timing recommendation for linaclotide (30 minutes before first meal) is particularly important as food can reduce its efficacy
• Taking either medication consistently at the same time each day helps establish a predictable bowel pattern
• If a dose is missed, patients should skip the missed dose and take the next dose at the regular time; they should not take two doses at the same time 2

By following these specific timing and administration guidelines, patients with IBS-C and CIC can maximize the efficacy of plecanatide and linaclotide while minimizing adverse effects.