For an adult with chronic idiopathic constipation refractory to diet and exercise, how should elobixibat be dosed, what are its contraindications, cautions, common adverse effects, alternative therapies, and monitoring recommendations?

Elobixibat for Chronic Idiopathic Constipation

Regulatory Status and Guideline Position

Elobixibat is not approved by the FDA and is not included in the 2023 AGA-ACG clinical practice guidelines for chronic idiopathic constipation in the United States. 1

• The 2023 joint American Gastroenterological Association–American College of Gastroenterology guideline systematically reviewed multiple agents but did not evaluate elobixibat, indicating it is not part of the standard U.S. treatment algorithm. 1
• Elobixibat's clinical development has been primarily in Japan, where it is approved and marketed. 1
• The absence from U.S. guidelines reflects lack of FDA approval and limited data in U.S. populations. 1

Recommended Treatment Algorithm for Chronic Constipation (U.S. Standard of Care)

First-Line Therapy

• Polyethylene glycol (PEG) 17 g once daily is the strongly recommended first-line treatment (moderate-certainty evidence). 2, 1
• Bisacodyl or sodium picosulfate for short-term or rescue therapy (strong recommendation, moderate-certainty evidence). 1

Second-Line Therapy (for patients not responding to OTC agents)

• Linaclotide (strong recommendation, moderate-certainty evidence). 2, 1
• Plecanatide (strong recommendation, moderate-certainty evidence). 2, 1
• Prucalopride (strong recommendation, moderate-certainty evidence). 2, 1
• Lubiprostone (conditional recommendation, low-certainty evidence). 2, 1

Additional Options

• Magnesium oxide (conditional recommendation, very low-certainty evidence). 1
• Lactulose (conditional recommendation, very low-certainty evidence). 1
• Senna (conditional recommendation, low-certainty evidence). 2, 1

Elobixibat: Japanese Clinical Data (For Academic Reference Only)

Mechanism of Action

• Elobixibat is a locally-acting ileal bile acid transporter (IBAT) inhibitor that increases bile acid delivery to the colon, stimulating both colonic motility and secretion. 3
• It selectively inhibits IBAT in vitro and dose-dependently inhibits bile acid absorption in vivo. 4

Dosing (Japanese Studies)

• Optimal dose: 10 mg once daily before breakfast (determined in phase 2 dose-finding study). 5
• Dose range studied: 5 mg, 10 mg, or 15 mg once daily. 5, 6
• Food significantly reduces systemic exposure by approximately 80%, so administration before breakfast is recommended. 7
• Patients may titrate between 5 mg, 10 mg, or 15 mg based on response and tolerability. 6

Efficacy (Japanese Trials)

• In the phase 3 randomized trial, elobixibat 10 mg increased spontaneous bowel movements to 6.4 per week versus 1.7 with placebo during week 1 (p<0.0001). 6
• In phase 2, the 10 mg and 15 mg doses increased spontaneous bowel movements to 5.7 and 5.6 times per week respectively, compared to 2.6 with placebo (p=0.0005 and p=0.0001). 5
• Efficacy was maintained throughout 52 weeks of continuous treatment in the open-label extension study. 6
• Elobixibat was equally effective in patients with or without constipation-predominant irritable bowel syndrome. 5

Adverse Effects

• Most common: mild abdominal pain (19-24% of patients) and diarrhea (13-15% of patients). 6
• In the 52-week trial, 48% of patients experienced an adverse drug reaction, most commonly mild gastrointestinal disorders (40%). 6
• No serious or severe adverse events occurred in the phase 2 study. 5
• One patient reported moderate inguinal hernia in the 52-week study. 6
• Adverse events were predominantly mild and gastrointestinal in nature. 7

Contraindications and Cautions

• No specific contraindications are detailed in the available Japanese clinical trial data. 5, 7, 6
• Drug-drug interaction studies suggest elobixibat may have a clinically slight inhibitory effect on P-glycoprotein. 4

Monitoring

• Japanese studies monitored serum LDL and HDL cholesterol levels, as elobixibat reduces LDL cholesterol. 7
• Plasma 7α-hydroxy-4-cholesten-3-one (C4) levels were measured as a pharmacodynamic marker of bile acid synthesis. 7
• Increased spontaneous bowel movement frequency correlated with higher C4 levels (R² = 0.59 at Week 2). 7

Additional Pharmacologic Effects

• Elobixibat reduces LDL cholesterol and increases serum GLP-1, suggesting potential benefits in metabolic syndrome. 3
• It increases HDL cholesterol levels while reducing LDL cholesterol. 7

Clinical Context

For U.S. practice, elobixibat cannot be recommended because it lacks FDA approval and is not included in evidence-based U.S. guidelines. 1 Clinicians should follow the established treatment algorithm starting with PEG, followed by linaclotide, plecanatide, or prucalopride for refractory cases. 2, 1 The Japanese data demonstrate elobixibat's efficacy and safety profile, but these findings have not been replicated in U.S. populations or resulted in FDA approval. 1, 6