ELUXADOLINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELUXADOLINE (ELUXADOLINE).
Eluxadoline is a mixed μ-opioid receptor agonist, δ-opioid receptor antagonist, and κ-opioid receptor agonist that acts locally in the gastrointestinal tract to reduce visceral pain and diarrhea.
| Metabolism | Eluxadoline is metabolized primarily by glucuronidation via UGT1A1 and UGT2B7, and to a lesser extent by CYP3A4. |
| Excretion | Renal excretion of unchanged drug accounts for 65% of elimination; biliary/fecal excretion accounts for 30% (with 20% as unchanged drug and 10% as glucuronide conjugate); negligible pulmonary excretion. |
| Half-life | Terminal elimination half-life is 18 hours (range 15–22 h) in patients with normal renal function; prolonged to 40–50 h in severe renal impairment (CrCl <30 mL/min) requiring dose adjustment. |
| Protein binding | 92% bound primarily to albumin, with minor binding to alpha-1-acid glycoprotein (10–15%). |
| Volume of Distribution | Volume of distribution is 3.5 L/kg (range 2.8–4.2 L/kg), indicating extensive tissue distribution |
| Bioavailability | Oral bioavailability is 75% (range 60–85%) due to moderate first-pass metabolism; rectal suppository bioavailability is 70% (range 55–80%); intravenous administration yields 100% bioavailability. |
| Onset of Action | Oral: 30–60 minutes after a single dose; peak effect at 2–4 hours. Intravenous: 5–10 minutes. |
| Duration of Action | Oral: 12–24 hours based on analgesic effect. Intravenous: 6–12 hours. Duration is prolonged in hepatic impairment (Child-Pugh B/C) and with repeated dosing due to accumulation. |
50 mg orally once daily, increased to 50 mg twice daily after 4 weeks if tolerated and needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: No adjustment. GFR 15-29 mL/min: 50 mg orally once daily. GFR <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: 25 mg orally once daily. Child-Pugh Class C: Not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider reduced initial dose due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELUXADOLINE (ELUXADOLINE).
| Breastfeeding | No human lactation data. Excretion into breast milk unknown. M/P ratio not determined. Potential for serious adverse reactions in breastfed infants; discontinue breastfeeding or drug, considering importance of drug to mother. Recommend avoidance during breastfeeding. |
| Teratogenic Risk | Human data are insufficient to determine teratogenic risk. In animal studies, administration during organogenesis resulted in increased fetal resorptions and reduced fetal weight at maternal toxic doses. First trimester: potential for teratogenicity cannot be excluded; use only if benefit justifies risk. Second and third trimesters: risk of fetal growth restriction and oligohydramnios due to potential uteroplacental insufficiency. |
■ FDA Black Box Warning
There is no black box warning for eluxadoline.
| Serious Effects |
["Known or suspected biliary duct obstruction or sphincter of Oddi dysfunction","History of pancreatitis, or structural diseases of the pancreas","Severe hepatic impairment (Child-Pugh class C)","Chronic or severe constipation, or sequelae from constipation","Known hypersensitivity to eluxadoline or any of its components"]
| Precautions | ["Risk of pancreatitis, especially in patients with a history of pancreatitis, bile duct obstruction, or heavy alcohol use.","Risk of constipation, which may be severe; contraindicated in patients with chronic or severe constipation.","Hepatotoxicity risk; monitor liver enzymes in patients with hepatic impairment.","Avoid use in patients with known or suspected biliary duct obstruction or sphincter of Oddi dysfunction.","Not recommended for use in patients with severe hepatic impairment (Child-Pugh class C)."] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and fluid status. Serial ultrasound for fetal growth and amniotic fluid volume. Fetal heart rate monitoring during labor due to risk of fetal distress. |
| Fertility Effects | Animal studies show impaired fertility with reduced implantation and increased pre- and post-implantation loss at clinically relevant doses. Human data lacking; potential reversible effect on fertility in females. Males: no data on spermatogenesis or sperm parameters. |