Why does Linzess (linaclotide) cause blood in the stool?

Why Linzess Causes Blood in Stool

Linzess (linaclotide) does not directly cause blood in the stool—blood in stool is not a recognized side effect of this medication and should prompt immediate evaluation for other causes of gastrointestinal bleeding. 1, 2

Understanding Linzess's Actual Side Effect Profile

Diarrhea is the primary and most common side effect of Linzess, occurring in approximately 16% of patients compared to 2% with placebo, but this diarrhea does not involve bleeding. 2, 3, 4

• The mechanism involves increased intestinal fluid secretion through guanylate cyclase-C receptor activation, which accelerates gastrointestinal transit and softens stools. 1, 3
• Diarrhea from Linzess is dose-dependent, with the 290 mcg dose (used for IBS-C) showing a 16.3% incidence versus 2.3% for placebo. 2
• This side effect is generally controllable by dose reduction and does not cause serious complications like severe dehydration or electrolyte disturbances in clinical trials. 2, 3

Why Blood in Stool Requires Alternative Explanation

If a patient on Linzess develops bloody stools, you must evaluate for other causes of gastrointestinal bleeding, as this is not an expected medication effect. 1

Common causes to investigate include:

• Hemorrhoids or anal fissures - particularly if the patient has developed diarrhea from Linzess, which could exacerbate pre-existing anorectal pathology. 1
• Inflammatory bowel disease - Crohn's disease or ulcerative colitis can present with bloody diarrhea and may have been the underlying cause of constipation symptoms. 1
• Colorectal polyps or cancer - especially in patients over 70 years of age, where angiodysplasia or diverticular disease are more common. 1
• Infectious colitis - bacterial or parasitic infections causing bloody diarrhea, which should be evaluated with stool studies. 1
• Ischemic colitis - particularly in elderly patients or those with cardiovascular risk factors. 1
• Medication-related mucosal injury - from concurrent NSAID use or other medications causing gastroduodenal ulceration. 1

Clinical Approach When Blood Appears

Perform digital rectal examination immediately to confirm the presence of blood and exclude anorectal pathology, as approximately 40% of rectal carcinomas are palpable. 1

Order stool studies including fecal lactoferrin or calprotectin to assess for inflammatory causes, and infectious workup if clinically indicated. 1

Consider colonoscopy or flexible sigmoidoscopy for patients with persistent or significant bleeding, particularly if accompanied by abdominal pain, weight loss, or other alarm features. 1

Temporarily discontinue Linzess if severe diarrhea is present, as this may be exacerbating an underlying bleeding source, though the medication itself is not causing the hemorrhage. 2, 3

Important Clinical Pitfall

Do not attribute bloody stools to Linzess and continue the medication without investigation—this represents a dangerous missed opportunity to diagnose serious underlying pathology such as colorectal cancer, inflammatory bowel disease, or ischemic colitis. 1 The British Society of Gastroenterology guidelines clearly identify diarrhea as the limiting side effect of linaclotide, not bleeding. 1