Lubistone

Approved Indications:

• Chronic Idiopathic Constipation (CIC) in adults.
• Opioid-Induced Constipation (OIC) in adults with chronic non-cancer pain.
• Irritable Bowel Syndrome with Constipation (IBS-C) in women aged ≥18 years.

Clinically Accepted Off-Label Uses:

• Functional constipation in elderly patients unresponsive to traditional laxatives.
• Neurogenic bowel dysfunction (e.g., spinal cord injury-related constipation) under specialist supervision.

Route of Administration: Oral (soft gelatin capsule).

Adult Dosage:

• CIC and OIC: 24 mcg orally twice daily with food and water.
• IBS-C (women ≥18 years): 8 mcg orally twice daily with food and water.

Geriatric Use:

• No dosage adjustment required; monitor for adverse effects such as nausea or hypotension.

Pediatric Use:

• Safety and efficacy not established in individuals under 18 years.

Renal Impairment:

• No dose adjustment necessary in mild to moderate renal impairment; use caution in severe impairment.

Hepatic Impairment:

• Use cautiously in moderate to severe hepatic impairment; safety not fully established.

Duration of Use:

• Treatment duration should be based on clinical response; periodic reassessment is recommended.

Lubiprostone is a locally acting chloride channel activator that specifically targets ClC-2 channels on the apical membrane of intestinal epithelial cells. Activation of these channels promotes chloride-rich fluid secretion into the intestinal lumen, which softens stools, increases intestinal motility, and facilitates spontaneous bowel movements. It does so without significant systemic absorption, minimizing systemic side effects and preserving serum electrolyte balance.

• Absorption: Low systemic availability (<10%).
• Distribution: Minimal systemic distribution; highly protein-bound.
• Metabolism: Rapidly metabolized by carbonyl reductase to inactive metabolites.
• Half-Life: Approximately 3 hours.
• Excretion:
• Metabolites excreted via urine (~60%) and feces (~30%).
• Minimal unchanged drug excreted.
• Onset of Action: Generally within 24 to 48 hours of starting therapy.

Pregnancy:

• No assigned FDA pregnancy category.
• Use only if clearly needed and the potential benefits outweigh potential risks. Animal studies show no teratogenicity, but human data are limited.

Lactation:

• Unknown whether lubiprostone is excreted in human milk. Minimal systemic absorption suggests low risk; however, caution is advised. Monitor infants for diarrhea or gastrointestinal discomfort.

• Primary Class: Gastrointestinal agent
• Subclass: Chloride channel activator (intestinal secretagogue)

• Known hypersensitivity to lubiprostone or any component of the formulation.
• Suspected or known mechanical gastrointestinal obstruction.
• Severe diarrhea or history of bowel perforation.

• Diarrhea: May cause severe diarrhea requiring dose reduction or discontinuation.
• Nausea: Common side effect; taking with food reduces incidence.
• Dyspnea: Transient shortness of breath reported shortly after dosing in some patients.
• Electrolyte Imbalance: Monitor patients with prolonged diarrhea.
• Use in GI Conditions: Caution in patients with known or suspected intestinal wall compromise or inflammatory bowel diseases.

Common (>5%):

• Nausea
• Diarrhea
• Abdominal pain
• Headache
• Flatulence

Less Common/Rare:

• Dyspnea (transient, often within 1 hour of dosing)
• Edema
• Syncope
• Hypotension
• Allergic reactions (rash, pruritus)

Onset and Severity:

• Side effects typically begin early in treatment and are generally mild to moderate. Nausea may improve with continued use or dose adjustment.

• Minimal CYP450 interaction: Lubiprostone is metabolized via non-CYP enzymatic pathways.
• Food: Should be taken with food to reduce nausea.
• Alcohol: No direct interactions reported, but may exacerbate GI side effects.
• No major drug-drug interactions reported.

• FDA Updates (2022–2023): Reaffirmed safety profile; emphasized cautious use in patients with severe hepatic impairment.
• ACG/AGA Guidelines: Include lubiprostone as a second-line agent for chronic idiopathic constipation and IBS-C, especially for patients unresponsive to fiber and osmotic laxatives.
• Preferred in opioid-induced constipation: Particularly when non-pharmacologic methods fail.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity: Store in a dry place in the original container.
• Light Protection: Protect from direct light.
• Handling:
• Do not remove desiccant.
• Store capsules in blister packs or sealed bottles until administration.
• Do not refrigerate or freeze.