VIBERZI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIBERZI (VIBERZI).
Guanylate cyclase-C agonist; increases intracellular cyclic guanosine monophosphate (cGMP) leading to activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting in increased intestinal fluid secretion and accelerated transit.
| Metabolism | Metabolized primarily in the gastrointestinal tract via hydrolysis to an active metabolite (MM-419447); minimal hepatic metabolism. |
| Excretion | Primarily fecal (approximately 95% of absorbed dose) with minimal renal excretion (<1%). |
| Half-life | Terminal elimination half-life is approximately 8-9 hours, supporting twice-daily dosing. |
| Protein binding | Approximately 98% bound to serum albumin. |
| Volume of Distribution | Volume of distribution is about 98 L (approximately 1.4 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 6%, due to extensive first-pass metabolism. |
| Onset of Action | Oral: Onset of clinical effect occurs within 1-2 hours after a single dose. |
| Duration of Action | Duration of action is approximately 12 hours, consistent with twice-daily dosing regimen. |
100 mg orally three times daily with meals.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended in patients with end-stage renal disease (eGFR <15 mL/min/1.73 m²) or those on dialysis. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended, but caution due to potential increased sensitivity and higher risk of constipation-related adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIBERZI (VIBERZI).
| Breastfeeding | It is not known whether eluxadoline is excreted in human milk; however, it is excreted in the milk of lactating rats at concentrations similar to maternal plasma. The M/P ratio in rats was approximately 0.8. Caution should be exercised when VIBERZI is administered to a nursing woman, and the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed infant. |
| Teratogenic Risk | VIBERZI (eluxadoline) has no adequate and well-controlled studies in pregnant women. In animal reproduction studies, oral administration of eluxadoline to pregnant rats and rabbits during organogenesis at doses up to 333 times and 67 times, respectively, the maximum recommended human dose (MRHD) of 100 mg twice daily based on AUC, resulted in no evidence of fetal harm. However, due to the lack of human data, the risk cannot be definitively characterized. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
Contraindicated in pediatric patients up to 6 years of age; avoid use in patients aged 6 to less than 18 years.
| Serious Effects |
["Pediatric patients up to 6 years of age","Mechanical gastrointestinal obstruction (known or suspected)"]
| Precautions | ["Risk of serious dehydration in pediatric patients (especially neonates and infants) due to diarrhea","Patients with chronic diarrhea may experience severe diarrhea and fluid/electrolyte losses; discontinue if severe diarrhea occurs"] |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring is required for VIBERZI therapy during pregnancy beyond routine prenatal care. However, due to the potential for gastrointestinal adverse effects (e.g., constipation, pancreatitis), monitoring for symptoms suggestive of pancreatitis, such as abdominal pain radiating to the back, nausea, vomiting, or elevated pancreatic enzymes, is advised. If pancreatitis is suspected, discontinue the drug and initiate appropriate management. |
| Fertility Effects | In animal studies, oral administration of eluxadoline to male and female rats at doses up to 333 times the MRHD based on AUC resulted in no impairment of fertility. No human data are available regarding effects on fertility. Potential reproductive effects in humans are unknown, but based on animal data, no significant fertility impairment is expected. |