Will 5mg of Elobixibat (Elobixibat) be effective for a patient with Chronic Idiopathic Constipation (CIC) who has already responded to 10mg of Elobixibat (Elobixibat)?

Dose Reduction of Elobixibat from 10mg to 5mg

Reducing elobixibat from 10mg to 5mg may provide inadequate efficacy for chronic idiopathic constipation, as the 5mg dose was not the optimal clinical dose identified in phase 2 trials, and patients in long-term studies were allowed to titrate down to 5mg only if they experienced tolerability issues—not as a standard maintenance strategy.

Evidence for Optimal Dosing

The phase 2b dose-finding study in Japanese patients with chronic constipation established that 10mg once daily is the clinically optimal dose 1. This trial compared 5mg, 10mg, and 15mg doses against placebo:

• The 10mg and 15mg doses significantly increased spontaneous bowel movements (5.7 ± 4.2 and 5.6 ± 3.5 times per week, respectively) compared to placebo (2.6 ± 2.9 times per week) 1
• The 5mg dose was not reported as achieving statistical significance in the primary endpoint, suggesting suboptimal efficacy at this lower dose 1
• Both 10mg and 15mg demonstrated similar efficacy, but 10mg was selected as the optimal clinical dose, likely balancing efficacy with tolerability 1

Long-Term Dosing Strategy

In the 52-week open-label phase 3 trial, patients were started on 10mg daily with the option to titrate to 5mg or 15mg based on individual response and tolerability 2:

• The study design allowed dose adjustment, but 10mg remained the standard starting and maintenance dose 2
• Dose reduction to 5mg was permitted for patients experiencing adverse effects (primarily mild abdominal pain in 24% and diarrhea in 15% of patients) 2
• The protocol did not support 5mg as an equivalent maintenance dose for patients responding well to 10mg 2

Clinical Implications for Your Patient

If your patient is responding well to 10mg without tolerability issues, reducing to 5mg risks losing therapeutic benefit:

• The dose-response relationship demonstrated that 5mg was below the threshold for optimal efficacy in the phase 2b trial 1
• Elobixibat's mechanism as an ileal bile acid transporter (IBAT) inhibitor requires sufficient inhibition to increase colonic bile acid delivery and stimulate both motor and secretory functions 3, 4
• Insufficient IBAT inhibition at 5mg may not maintain the accelerated colonic transit and increased stool frequency achieved at 10mg 4

When Dose Reduction Is Appropriate

Reduce to 5mg only if the patient experiences:

• Excessive diarrhea or loose stools that interfere with quality of life 2
• Bothersome abdominal pain or cramping 2
• Other gastrointestinal adverse effects that are dose-related 1

Alternative Management Strategy

If cost or other non-medical factors are driving the dose reduction consideration:

• Consider that elobixibat is not included in current American Gastroenterological Association-American College of Gastroenterology guidelines as a recommended treatment option in the United States 5
• First-line alternatives include polyethylene glycol (PEG) 17g daily, which costs $10-45 monthly compared to prescription agents 6
• Second-line options include linaclotide (72-145μg daily), plecanatide (3mg daily), or prucalopride (1-2mg daily) if the patient requires prescription therapy 6

Common Pitfall to Avoid

Do not assume that "some drug is better than less drug" when reducing doses below the established therapeutic threshold. The phase 2 trial specifically tested 5mg and found it insufficient to establish the optimal clinical dose, which is why 10mg was selected for phase 3 development 1. Reducing to 5mg in a responding patient essentially creates a subtherapeutic dosing scenario without evidence of maintained efficacy.