| Drug class |
Mixed μ‑opioid receptor agonist, κ‑opioid receptor agonist, σ‑receptor antagonist. |
Guanylate‑cyclase‑C (GC‑C) agonist – a peptide that stimulates fluid secretion in the gut. |
| How it works |
Modulates GI motility and sensation by binding to opioid receptors in the gut wall, slowing transit and reducing pain. |
Activates GC‑C receptors on intestinal epithelial cells → ↑ cyclic‑GMP → increased chloride and bicarbonate secretion → fluid secretion and softer stools. |
| Typical dose |
100 mg PO twice daily (BID) |
145 µg PO once daily (OD) |
| Take with food? |
Can be taken with or without food. |
Take on an empty stomach; do not take within 1 hour after a meal. |
| Onset of action |
1–2 weeks to see full benefit |
1–2 weeks; some patients notice improvement sooner. |
| Half‑life |
~5–6 hrs (but effects last >24 hrs) |
~1–1.5 hrs (rapid clearance) |
| Renal / hepatic considerations |
Mainly fecal excretion; mild hepatic metabolism. Avoid in severe renal impairment. |
Excreted unchanged by kidneys; safe in mild‑to‑moderate renal impairment. |
| Major side‑effects |
• Nausea, vomiting, abdominal pain
• Diarrhea (often early in treatment)
• Constipation (more common than Linzess)
• Rarely, pancreatitis or gallbladder problems (black‑box warning) |
• Diarrhea (most common)
• Abdominal cramping / bloating
• Headache, flushing
• Rare hypokalemia (monitor K⁺ in patients on potassium‑wasting meds) |
| Contraindications |
• History of pancreatitis or gallbladder disease
• Severe constipation or known colonic obstruction
• Hypersensitivity to eluxadoline |
• Known or suspected colonic obstruction, ileus, or severe constipation
• Hypersensitivity to linaclotide |
| Drug interactions |
• Opioids or other CNS depressants (additive sedation)
• Drugs that alter CYP2C19 (may affect levels) |
Minimal; no major drug‑drug interactions reported. |
| Special populations |
• Not approved for pregnancy or lactation (data limited)
• Not approved for children or adolescents |
• Not approved for pregnancy or lactation (data limited)
• Approved for chronic constipation in adults and in children 6 + years (but not for IBS‑D in pediatrics) |
| Cost / insurance |
Generally more expensive; many patients report higher copays. |
Slightly cheaper on average; still can be costly without insurance coverage. |
| Monitoring |
• Watch for signs of pancreatitis (abdominal pain radiating to back, nausea, vomiting, elevated lipase) – if present, discontinue immediately.
• Monitor bowel habits and constipation. |
• Check potassium if on diuretics or other potassium‑wasting meds.
• Monitor for severe diarrhea or dehydration. |
| Efficacy (clinical data) |
In trials, ~25–30 % of patients achieved ≥30 % reduction in |