I am still having diarrhea after starting Linzess (linaclotide) for severe constipation; what should I do?

Managing Diarrhea After Starting Linzess for Severe Constipation

If you are experiencing diarrhea after starting Linzess, you should immediately reduce the dose or temporarily suspend the medication, then restart at a lower dose once the diarrhea resolves. 1, 2, 3

Understanding Diarrhea as the Primary Side Effect

Diarrhea is the most common and expected adverse effect of Linzess, occurring in approximately 16% of patients compared to only 2-3% on placebo. 4, 2 This is a direct consequence of the medication's mechanism—it increases intestinal fluid secretion to relieve constipation. 1

• Severe diarrhea occurs in about 2% of patients taking standard doses (145 mcg or 290 mcg). 3
• Approximately 3-5% of patients discontinue Linzess specifically due to diarrhea. 4, 2
• In post-marketing surveillance, severe diarrhea has been associated with dizziness, syncope, hypotension, and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization. 3

Immediate Management Algorithm

Step 1: Assess Severity

• If you have severe diarrhea (multiple watery stools per day, dehydration symptoms, dizziness, or weakness), suspend Linzess immediately and rehydrate. 3
• Seek medical attention if you experience signs of dehydration, electrolyte imbalance, or cannot maintain adequate oral hydration. 3

Step 2: Dose Reduction Strategy

• If currently taking 145 mcg daily for chronic constipation, reduce to 72 mcg daily once diarrhea resolves. 1, 4
• The 72 mcg dose maintains efficacy while significantly reducing diarrhea rates. 1
• Take the medication on an empty stomach at least 30 minutes before your first meal to optimize absorption and minimize side effects. 1

Step 3: Consider Alternative Secretagogue

• If diarrhea persists even at the lower 72 mcg dose, switch to lubiprostone (8 mcg twice daily), which has significantly lower diarrhea rates (4.3% vs 16.3%) while maintaining efficacy for constipation. 2

Important Caveats and Monitoring

Risk Factors for Severe Complications:

• You are at higher risk for electrolyte abnormalities if you take diuretics or other medications affecting sodium balance. 1, 2
• Monitor for signs of hyponatremia (confusion, weakness, headache) and hypokalemia (muscle weakness, cramping, irregular heartbeat). 3

Medication Interactions:

• Do not combine Linzess with other laxatives initially, as this enhances the laxative effect and increases diarrhea risk. 4, 5
• The diarrhea may reduce gastrointestinal absorption of other oral medications you are taking. 5

What NOT to Do:

• Do not continue taking the same dose hoping the diarrhea will resolve on its own—dose reduction is necessary. 1, 2
• Do not take Linzess sporadically or "as needed"—it should be taken continuously at the appropriate dose for optimal efficacy. 6
• Do not start both Linzess and over-the-counter laxatives simultaneously if you are treatment-naive, as this causes excessive bowel response. 4

Long-Term Considerations

• Once you find a tolerable dose, Linzess can be maintained long-term without tachyphylaxis (loss of effectiveness over time). 6
• The most common reasons for discontinuation over the first year are loss of efficacy and insurance barriers, not adverse events, suggesting most patients who tolerate the initial period do well long-term. 1
• If the lower 72 mcg dose does not adequately control your constipation, you may need to add back an over-the-counter osmotic laxative like polyethylene glycol (Miralax) rather than increasing the Linzess dose. 4