Elobixibat

Usage

• Elobixibat is prescribed for the treatment of chronic idiopathic constipation (CIC) in adults. It is specifically indicated for CIC cases not associated with organic diseases.
• Pharmacological classification: Laxative, specifically an ileal bile acid transporter (IBAT) inhibitor.
• Mechanism of Action: Elobixibat works by inhibiting IBAT, which is responsible for reabsorbing bile acids in the ileum (the final section of the small intestine). This inhibition increases the flow of bile acids into the colon. The higher concentration of bile acids in the colon stimulates water and electrolyte secretion, increases colonic motility, and ultimately softens the stool and promotes bowel movements.

Alternate Names

• International Nonproprietary Name (INN): Elobixibat
• Brand names: Goofice®

How It Works

• Pharmacodynamics: Elobixibat increases the concentration of bile acids in the colon, leading to increased fluid secretion, enhanced colonic motility, and softer stools. This promotes more frequent and easier bowel movements.
• Pharmacokinetics:
  • Absorption: Elobixibat is orally administered and absorbed in the gastrointestinal tract. Food does not significantly affect absorption.
  • Metabolism: Elobixibat is minimally metabolized. The majority is excreted unchanged. A minor metabolite is a monohydroxy form.
  • Elimination: Primarily eliminated via fecal excretion. Urinary excretion is negligible (around 0.01%).
• Mode of Action: Elobixibat selectively inhibits IBAT located on the epithelial cells of the terminal ileum. This blocks the enterohepatic circulation of bile acids, allowing more bile acids to enter the colon.
• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Elobixibat is an IBAT inhibitor. It also inhibits P-glycoprotein (P-gp) in vitro, which may affect the pharmacokinetics of P-gp substrates.
• Elimination Pathways: Primarily fecal excretion, with minimal urinary excretion.

Dosage

Standard Dosage

Adults:

• The usual starting dose is 10 mg once daily, taken orally before a meal.
• The dose can be adjusted based on the patient’s response, with a maximum dose of 15 mg per day.

Children:

• The safety and efficacy of elobixibat have not been established in pediatric patients. It is not recommended for use in children.

Special Cases:

• Elderly Patients: Caution should be exercised in elderly patients due to potential age-related decline in physiological functions. Dose reduction may be necessary.
• Patients with Renal Impairment: No specific dose adjustment is recommended, as renal excretion is negligible.
• Patients with Hepatic Dysfunction: Caution is recommended for patients with severe hepatic impairment.
• Patients with Comorbid Conditions: Caution is advised for patients with biliary obstruction or reduced bile acid secretion, as elobixibat might not be effective in these cases.

Clinical Use Cases

Elobixibat is specifically indicated for chronic idiopathic constipation and is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

Dose adjustments may be necessary based on individual patient response and tolerance. Dose reduction should be considered if abdominal pain or diarrhea occurs.

Side Effects

Common Side Effects:

• Abdominal pain
• Diarrhea
• Nausea
• Abdominal discomfort
• Flatulence

Rare but Serious Side Effects:

• Severe abdominal pain
• Persistent diarrhea
• Allergic reactions (e.g., rash, hives, itching)

Long-Term Effects:

• Limited data are available on the long-term effects of elobixibat use.

Adverse Drug Reactions (ADR):

• Clinically significant ADRs requiring intervention primarily involve severe gastrointestinal symptoms.

Contraindications

• Hypersensitivity to elobixibat or any of its components.
• Documented or suspected intestinal obstruction associated with a tumor or hernia.

Drug Interactions

• Bile acid sequestrants (e.g., cholestyramine, colestipol): May reduce the effectiveness of elobixibat.
• Aluminum-containing antacids: May decrease elobixibat’s efficacy.
• P-gp substrates (e.g., digoxin, dabigatran etexilate): Elobixibat may increase plasma concentrations of these drugs.
• Midazolam: Elobixibat may decrease plasma levels of midazolam.

Pregnancy and Breastfeeding

• Pregnancy: Elobixibat should be used during pregnancy only if the potential benefit outweighs the risk to the fetus. Animal studies have shown adverse effects at high doses.
• Breastfeeding: It is recommended that women avoid breastfeeding while taking elobixibat. Animal studies have shown excretion of elobixibat in breast milk.

Drug Profile Summary

• Mechanism of Action: IBAT inhibitor, increases bile acid concentration in the colon, promoting bowel movements.
• Side Effects: Abdominal pain, diarrhea, nausea, flatulence.
• Contraindications: Hypersensitivity, intestinal obstruction.
• Drug Interactions: Bile acid sequestrants, aluminum antacids, P-gp substrates, midazolam.
• Pregnancy & Breastfeeding: Use with caution during pregnancy; avoid breastfeeding while taking.
• Dosage: 10 mg once daily, adjustable up to 15 mg; taken orally before meals.
• Monitoring Parameters: Stool frequency, consistency, and any adverse effects.

Popular Combinations

Elobixibat is typically used as monotherapy. Combination use with other laxatives is not generally recommended unless specifically indicated by a physician.

Precautions

• General Precautions: Assess patients for potential contraindications and drug interactions before initiating therapy. Monitor for gastrointestinal side effects.
• Specific Populations: Use with caution in pregnant women, avoid during breastfeeding, and not recommended for children. Consider dose reduction in the elderly.
• Lifestyle Considerations: No specific lifestyle restrictions are associated with elobixibat use. However, maintaining adequate hydration is generally recommended for patients with constipation.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Elobixibat?

A: The recommended starting dose for adults is 10 mg orally once daily before a meal. The dose can be adjusted based on individual response, with a maximum dose of 15 mg per day. It is not recommended for children.

Q2: How does Elobixibat work?

A: Elobixibat inhibits IBAT in the terminal ileum, increasing the amount of bile acids reaching the colon. This stimulates bowel movements.

Q3: What are the common side effects of Elobixibat?

A: The most common side effects are abdominal pain, diarrhea, nausea, and flatulence.

Q4: Who should not take Elobixibat?

A: Patients with hypersensitivity to elobixibat or with known or suspected intestinal obstruction should not take this medication.

Q5: Can Elobixibat be used during pregnancy?

A: Elobixibat should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Q6: Can Elobixibat be used while breastfeeding?

A: It is recommended to avoid breastfeeding while taking elobixibat.

Q7: Does Elobixibat interact with other medications?

A: Yes, it can interact with bile acid sequestrants, aluminum antacids, P-gp substrates (like digoxin and dabigatran), and midazolam.

Q8: How long does it take for Elobixibat to work?

A: In clinical trials, many patients experienced a bowel movement within 24 hours of the first dose.

Q9: What should I do if I miss a dose of Elobixibat?

A: Take the missed dose before your next meal. Do not double the dose.

Q10: Are there any long-term effects of Elobixibat?

A: Limited data are available on the long-term effects of elobixibat use. Long-term monitoring of patients is recommended.