What is the recommended treatment and dosage of Elobixat (Elobixibat) for constipation?

Elobixibat for Chronic Constipation

The recommended dosage of elobixibat for chronic constipation is 10 mg once daily taken orally before breakfast, which can be titrated to 5 mg or 15 mg based on individual response and tolerability. 1, 2

Mechanism of Action

Elobixibat is a locally-acting ileal bile acid transporter (IBAT) inhibitor that increases bile acid delivery to the colon, representing a novel class of constipation treatment with dual effects on colonic function 3:

• Accelerates colonic transit by increasing intracolonic bile acid concentrations 3, 2
• Stimulates colonic secretion, drawing water into the intestine 3

This mechanism differs fundamentally from existing osmotic laxatives and secretagogues, as it works by inhibiting bile acid reabsorption rather than directly adding osmotic agents or stimulating chloride channels 4.

Dosing Recommendations

Initial Dosing

• Start with 10 mg once daily before breakfast 1, 2, 5
• Food consumption significantly reduces systemic exposure by approximately 80%, making pre-breakfast administration critical for optimal efficacy 5

Dose Titration

The dose can be adjusted based on clinical response 2:

• Decrease to 5 mg daily if gastrointestinal side effects occur 2
• Increase to 15 mg daily if constipation symptoms are inadequately controlled 2
• Dose adjustments should be made after assessing response during the first 1-2 weeks of treatment 1, 2

Maximum Dose

• 15 mg once daily is the established maximum effective dose 1, 2
• Doses up to 20 mg have been studied and found safe, but 10 mg was determined to be the clinically optimal dose in phase 2 trials 1, 5

Efficacy Evidence

The phase 3 randomized controlled trial demonstrated robust efficacy 2:

• Spontaneous bowel movements increased from baseline to 6.4 per week (95% CI 5.3-7.6) with elobixibat 10 mg versus 1.7 per week with placebo (p<0.0001) during week 1 of treatment 2
• Efficacy was maintained throughout 52 weeks of treatment in the open-label extension study 2
• Equally effective in patients with or without constipation-predominant IBS, suggesting broad applicability 1

The dose-response relationship shows that increased spontaneous bowel movement frequency correlates with higher dosage and elevated plasma C4 levels (a marker of bile acid synthesis, R² = 0.5929 at Week 2) 5.

Safety and Tolerability

Common Adverse Events

The most frequent side effects are mild and gastrointestinal in nature 2, 5:

• Abdominal pain: 19-24% of patients (mostly mild) 2
• Diarrhea: 13-15% of patients 2
• These symptoms are dose-dependent and typically mild 1, 2

Long-Term Safety

In the 52-week open-label trial 2:

• 48% of patients experienced adverse drug reactions, predominantly mild gastrointestinal disorders (40%) 2
• No serious adverse events directly attributed to elobixibat occurred 1, 2
• Only one moderate adverse drug reaction (inguinal hernia) was reported, though causality is unclear 2

Additional Benefits

Beyond constipation relief, elobixibat demonstrates metabolic benefits 3, 5:

• Reduces LDL cholesterol through increased bile acid excretion 3, 5
• Increases serum GLP-1 levels, suggesting potential benefits in metabolic syndrome 3
• Does not alter HDL cholesterol levels 5

Clinical Positioning

While not included in the 2023 AGA-ACG guidelines for chronic idiopathic constipation 6, elobixibat represents a mechanistically distinct option compared to standard therapies. It may be particularly useful as:

• Second-line therapy when osmotic laxatives (PEG 17 g daily 6) or secretagogues (lubiprostone 24 μg BID 6) provide inadequate relief 3
• First-line option for patients with documented colonic bile acid deficiency 3

Important Caveats

• Must be taken before breakfast to ensure adequate absorption and efficacy; food reduces exposure by 80% 5
• Patients should be counseled about the possibility of mild abdominal discomfort and diarrhea, particularly during dose titration 2
• Currently approved in Japan; availability in other regions may be limited 2, 4
• Drug-drug interaction studies suggest potential mild inhibition of P-glycoprotein, requiring consideration when co-administering P-gp substrates 4