Does Linzess Cause Low Sodium?
Yes, Linzess (linaclotide) can cause hyponatremia (low sodium), but this occurs specifically in the context of severe diarrhea—the FDA drug label explicitly warns that severe diarrhea associated with electrolyte abnormalities including hyponatremia requiring hospitalization has been reported in post-marketing experience. 1
Mechanism and Clinical Context
Hyponatremia is not a direct pharmacologic effect of linaclotide itself, but rather a consequence of severe diarrhea leading to volume depletion and electrolyte losses 1
The FDA label specifically states that "severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or intravenous fluid administration have been reported in patients treated with LINZESS" 1
Linaclotide works as a guanylate cyclase-C agonist that increases intestinal fluid secretion and accelerates gastrointestinal transit, which explains why excessive diarrhea can lead to electrolyte disturbances 2, 3
Risk Factors and Incidence
Diarrhea is the most common adverse reaction, occurring in 20% of patients treated with linaclotide 290 mcg (for IBS-C) compared to 3% with placebo 1
Severe diarrhea occurs in approximately 2% of patients on 145 mcg or 290 mcg doses 1
About 5% of patients discontinue linaclotide due to diarrhea 1
The majority of diarrhea cases start within the first 2 weeks of treatment 1
Critical Management Points
If severe diarrhea occurs, immediately suspend linaclotide dosing and rehydrate the patient—this is the FDA-mandated approach to prevent or treat electrolyte abnormalities including hyponatremia. 1
Monitor for warning signs: dizziness, syncope, or hypotension accompanying diarrhea, as these suggest volume depletion and potential electrolyte disturbances 1
In patients who develop severe diarrhea, check electrolytes including sodium and potassium, as both hyponatremia and hypokalemia have been reported 1
Consider dose reduction (from 290 mcg to 145 mcg, or from 145 mcg to 72 mcg) in patients experiencing problematic diarrhea before it becomes severe 2
Important Caveats
This is a hypovolemic hyponatremia (due to fluid and sodium losses from diarrhea), not the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or other mechanisms 4
The risk is highest in vulnerable populations who may not adequately compensate for fluid losses, though the drug is contraindicated in children under 2 years due to dehydration risk 1
Patients on concurrent medications that affect sodium balance (such as diuretics) may be at higher risk, though this is not specifically addressed in the linaclotide literature 5