Elobixibat Dose Titration
Elobixibat should be initiated at 10 mg once daily before breakfast, with dose adjustment to 5 mg daily (if not tolerated) or 15 mg daily (if inadequate response) based on individual patient response and tolerability. 1
Standard Dosing Protocol
- Starting dose: 10 mg once daily taken orally before breakfast 1
- Dose reduction: Decrease to 5 mg daily if gastrointestinal side effects (particularly abdominal pain or diarrhea) are not tolerated 1
- Dose escalation: Increase to 15 mg daily if constipation relief is inadequate at the 10 mg dose 1
Clinical Context for This Patient
In a patient with IBS-C who has failed both elobixibat and prucalopride, the issue is likely not inadequate dosing but rather treatment failure requiring a different therapeutic approach. The British Society of Gastroenterology identifies linaclotide as the most efficacious secretagogue for IBS-C, making it the preferred next-line agent after failure of other treatments. 2
Alternative Treatment Pathway
- Linaclotide 290 mcg once daily should be considered as the next therapeutic option, as it represents a different mechanism of action (guanylate cyclase-C agonist) compared to elobixibat (ileal bile acid transporter inhibitor) and prucalopride (5-HT4 agonist) 3, 4
- Linaclotide has the strongest evidence base for IBS-C with high-quality data supporting efficacy for both abdominal pain and bowel function 2
Elobixibat Efficacy and Safety Profile
- In phase 3 trials, elobixibat 10 mg increased spontaneous bowel movements to a mean of 6.4 per week versus 1.7 with placebo during the first week of treatment 1
- Most common adverse effects: Mild abdominal pain (19-24% of patients) and diarrhea (13-15% of patients) 1
- Long-term safety data from 52-week trials showed 48% of patients experienced adverse drug reactions, predominantly mild gastrointestinal disorders 1
Important Caveats
- Elobixibat works by increasing intracolonic bile acid concentrations, making it most effective in patients with bile acid deficiency-related constipation 5
- Treatment failure with elobixibat suggests the patient may not have bile acid deficiency as the primary pathophysiologic mechanism, warranting a switch to agents with different mechanisms rather than dose escalation 5
- The combination of failed elobixibat and prucalopride indicates the need for secretagogues (linaclotide, lubiprostone, or plecanatide) or consideration of gut-brain neuromodulators if pain is prominent 2, 4