Laxibat

Approved Indications:

• Chronic Idiopathic Constipation (CIC):
• Indicated for the treatment of chronic idiopathic constipation in adults when lifestyle and dietary changes are insufficient.

Clinically Accepted/Investigational Uses:

• Constipation in Patients with Type 2 Diabetes Mellitus:
• Under investigation as a treatment to manage chronic constipation commonly associated with diabetic neuropathy.
• Constipation-Predominant Irritable Bowel Syndrome (IBS-C):
• Investigated for relieving constipation and abdominal discomfort in IBS-C patients.

Adults:

• Recommended Dose:
• 10 mg once daily, taken orally before breakfast.
• Dose Adjustment:
• If response is inadequate after one week, dosage may be increased to 15 mg once daily.

Pediatric Use:

• Safety and efficacy in children and adolescents under 18 years of age have not been established; not recommended.

Elderly:

• No specific dose adjustment required. Start at the lowest effective dose, monitor closely for tolerability.

Renal Impairment:

• No dosage adjustment required in mild to moderate renal impairment.
• Use with caution in severe renal impairment due to limited data.

Hepatic Impairment:

• No dosage adjustment required. However, use with caution in severe hepatic dysfunction due to lack of clinical experience.

Route of Administration:

• Oral; should be taken once daily before breakfast, preferably with water.

Elobixibat is a selective ileal bile acid transporter (IBAT) inhibitor, which blocks the reabsorption of bile acids in the terminal ileum. This inhibition increases the concentration of bile acids entering the colon. Bile acids stimulate colonic secretion and motility, enhancing water secretion into the bowel and increasing stool frequency and ease of defecation. This mechanism is peripheral and gut-specific, avoiding central nervous system effects, and promotes a natural laxative response without significant electrolyte imbalance.

• Absorption:
• Systemic absorption is minimal; primarily acts locally in the intestinal tract.
• Peak plasma concentration (if measurable) is reached within 1–2 hours.
• Bioavailability:
• Very low systemic bioavailability (<1%).
• Distribution:
• Plasma protein binding is high (~99.9%) in the small amount that is absorbed.
• Metabolism:
• Minimally metabolized; undergoes slight hepatic transformation.
• Elimination:
• Excreted mostly unchanged via feces.
• Terminal half-life: 3–7 hours (in the small absorbed portion).

• Pregnancy:
• There are no adequate and well-controlled studies in pregnant women.
• Use only if the potential benefit justifies the potential risk to the fetus.
• Classified as Pregnancy Category Not Assigned (FDA).
• Lactation:
• Unknown whether elobixibat is excreted in human milk.
• Caution is advised; the decision to continue breastfeeding should weigh the benefits and potential risks.
• Fertility:
• No adverse effects on fertility were observed in animal studies.

• Primary Class: Gastrointestinal Agent
• Subclass: Ileal Bile Acid Transporter (IBAT) Inhibitor / Laxative (Peripheral)

• Known hypersensitivity to elobixibat or any component of the formulation
• Suspected or confirmed intestinal obstruction
• Severe inflammatory conditions of the gastrointestinal tract (e.g., Crohn’s disease, ulcerative colitis)
• Severe liver dysfunction (due to lack of sufficient clinical data)
• Galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (if excipients are contraindicated)

• Gastrointestinal Effects:
• Use with caution in patients with known or suspected intestinal obstruction, bile acid diarrhea, or inflammatory bowel disease.
• Electrolyte Imbalance:
• Rare, but monitor if used chronically or in patients with fluid/electrolyte disorders.
• Abdominal Pain or Diarrhea:
• Common early side effects; may necessitate dose adjustment or discontinuation.
• Hepatic Impairment:
• Limited data in severe hepatic dysfunction; use with caution.
• Clinical Monitoring:
• Monitor for signs of excessive diarrhea, dehydration, or electrolyte imbalance, especially in elderly or debilitated patients.

Common Adverse Effects (≥1%):

• Gastrointestinal:
• Abdominal pain
• Diarrhea
• Flatulence
• Nausea
• Abdominal bloating
• Increased bowel movements

Less Common:

• Headache
• Dizziness

Serious/Rare Effects:

• Severe diarrhea with dehydration
• Hypersensitivity reactions (rash, urticaria – very rare)
• Bowel obstruction or exacerbation of underlying GI disease (rare)

Onset & Severity:

• Side effects typically occur within the first few days of therapy
• Most are mild to moderate and transient

• Bile Acid Sequestrants (e.g., cholestyramine, colestipol):
• May reduce elobixibat efficacy by binding bile acids. Separate dosing by ≥4 hours.
• Oral Contraceptives and Hormones:
• No clinically relevant interactions reported; use standard precautions.
• Warfarin or Other CYP450 Substrates:
• No significant CYP450 enzyme inhibition or induction observed.

Enzyme Systems Involved:

• Not metabolized by CYP enzymes to a clinically relevant extent
• Minimal systemic involvement; negligible drug interaction potential

• Recent Clinical Data:
• Clinical trials continue to show efficacy and safety for long-term use in CIC.
• Evaluated in patients with diabetic neuropathy-related constipation, showing beneficial outcomes.
• Guideline Inclusion:
• Recognized in some gastroenterology society treatment pathways as a novel and effective approach to managing CIC, especially in patients unresponsive to bulk-forming or osmotic laxatives.
• Post-Marketing Surveillance:
• No major safety concerns reported; favorable tolerability profile maintained.

• Temperature:
• Store at 20°C to 25°C (68°F to 77°F)
• Excursions permitted between 15°C and 30°C (59°F to 86°F)
• Humidity & Light Protection:
• Store in original container
• Protect from excessive moisture and direct light
• Handling Precautions:
• Do not use if tablets are broken or expired
• No refrigeration or special reconstitution required
• Keep out of reach of children