Viberzi
(eluxadoline)Dosage & Administration
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Viberzi Prescribing Information
VIBERZI is indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D).
The recommended dosage of VIBERZI is 100 mg taken orally twice daily with food.
The recommended dosage of VIBERZI is 75 mg taken orally twice daily with food in patients:
- unable to tolerate the 100 mg dose of VIBERZI [see Adverse Reactions ( 6.1)].
- receiving concomitant OATP1B1 inhibitors [see Drug Interactions ( 7)].
- with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment [see Use in Specific Populations ( 8.6)].
- with moderate or severe renal impairment (eGFR less than 60 mL/min/1.73 m2); and in patients with end stage renal disease (ESRD) not yet on dialysis (eGFR less than 15 mL/min/1.73 m2) [see Use in Specific Populations ( 8.7)].
Discontinue VIBERZI in patients who develop severe constipation [see Warnings and Precautions ( 5.4)].
Instruct patients if they miss a dose, take the next dose at the regular time and not to take 2 doses at the same time to make up for a missed dose.
- 75 mg tablets: capsule-shaped tablets are coated in pale-yellow to light tan color debossed with “FX75” on one side. Each tablet contains 75 mg eluxadoline.
- 100 mg tablets: capsule-shaped tablets are coated in pink-orange to peach color debossed with “FX100” on one side. Each tablet contains 100 mg eluxadoline.
8.1 Pregnancy
Risk Summary
There are no studies with VIBERZI in pregnant women that inform any drug-associated risks. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. In animal reproduction studies, oral and subcutaneous administration of eluxadoline to rats and rabbits during organogenesis at doses approximately 51 and 115 times the human exposure after a single oral dose of 100 mg, respectively, demonstrated no teratogenic effects. In a pre- and postnatal development study in rats, no adverse effects were observed in offspring with oral administration of eluxadoline at doses approximately 10 times the human exposure (see Data).
Data
Animal Data
Eluxadoline administered as combined oral (1000 mg/kg/day) and subcutaneous (5 mg/kg/day) doses during the period of organogenesis to rats and rabbits (exposures about 51 and 115 times, respectively, the human AUC of 24 ng.h/mL after a single oral dose of 100 mg) did not cause any adverse effects on embryofetal development. A pre- and postnatal development study in rats showed no evidence of any adverse effect on pre- and postnatal development at oral doses of eluxadoline up to 1000 mg/kg/day (with exposures about 10 times the human AUC of 24 ng.h/mL after a single oral dose of 100 mg). In the same study, eluxadoline was detected in the milk of lactating rats administered oral doses of 100, 300 and 1000 mg/kg/day (with exposures about 1.8, 3 and 10 times, respectively, the human AUC of 24 ng.h/mL after a single oral dose of 100 mg). Milk samples were collected from six lactating females per group on lactation day 12. Mean concentrations of eluxadoline in the milk of lactating rats on lactation day 12 were 2.78, 5.49 and 44.02 ng/mL at 100, 300 and 1000 mg/kg/day, respectively.
8.2 Lactation
Risk Summary
No data are available regarding the presence of eluxadoline in human milk, the effects of eluxadoline on the breastfed infant, or the effects of eluxadoline on milk production. However, eluxadoline is present in rat milk [see Use in Specific Populations ( 8.1)].
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VIBERZI and any potential adverse effects on the breastfed infant from VIBERZI or from the underlying maternal condition.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Juvenile Toxicology Data
Eluxadoline was orally administered to juvenile rats at 500, 750, and 1500 mg/kg/day (about 16, 54 and 30 times, respectively, the human AUC of 24 ng.h/mL after a single oral dose of 100 mg) for 4 weeks. There were no adverse physiologic effects related to eluxadoline. Based on these results, the NOAEL for male and female juvenile rats was 1500 mg/kg/day (about 30 times the human AUC of 24 ng.h/mL after a single oral dose of 100 mg).
8.5 Geriatric Use
Of 1795 IBS-D patients in clinical trials of VIBERZI who received 75 mg or 100 mg twice daily, 139 (7.7%) were at least 65 years of age, while 15 (0.8%) were at least 75 years old. No overall differences in effectiveness were observed between these patients and younger patients. There were no overall differences in the types of adverse reactions observed between elderly and younger patients; however, a higher proportion of elderly patients than younger patients experienced adverse reactions (66% vs 59%), serious adverse reactions (9% vs 4%), and gastrointestinal adverse reactions (39% vs 28%).
8.6 Hepatic Impairment
Plasma concentrations of eluxadoline increase in patients with hepatic impairment [see Clinical Pharmacology ( 12.3)].
VIBERZI is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) as plasma concentrations of eluxadoline increase significantly (16-fold) and there is no information to support the safety of VIBERZI in these patients.
In patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, plasma concentrations of eluxadoline increase to a lesser extent (6- and 4-fold, respectively). Administer VIBERZI at a reduced dose of 75 mg twice daily to these patients [see Dosage and Administration ( 2)]. Monitor patients with any degree of hepatic impairment for impaired mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery and for other eluxadoline-related adverse reactions [see Adverse Reactions ( 6.1)].
8.7 Renal Impairment
In patients with severe renal impairment (eGFR 15 to 30 mL/min/1.73 m2) and ESRD not yet on dialysis (eGFR less than 15 mL/min/1.73 m2), exposure of eluxadoline was increased compared to healthy subjects with normal renal function [see Clinical Pharmacology ( 12.3)]. Administer VIBERZI at a reduced dose of 75 mg twice daily to patients with moderate or severe renal impairment and in patients with ESRD not yet on dialysis [see Dosage and Administration ( 2)]. No dosage adjustment is needed for patients with mild renal impairment.
VIBERZI is contraindicated in patients:
- Without a gallbladder. These patients are at increased risk of developing serious adverse reactions of pancreatitis and/or sphincter of Oddi spasm [see Warnings and Precautions ( 5.1, 5.2)]
- With known or suspected biliary duct obstruction; or sphincter of Oddi disease or dysfunction. These patients are at increased risk for sphincter of Oddi spasm [see Warnings and Precautions ( 5.1)].
- With alcoholism, alcohol abuse or alcohol addiction, or in patients who drink more than 3 alcoholic beverages per day. These patients are at increased risk for acute pancreatitis [see Warnings and Precautions ( 5.1)].
- With a history of pancreatitis; or structural diseases of the pancreas, including known or suspected pancreatic duct obstruction. These patients are at increased risk for acute pancreatitis [see Warnings and Precautions ( 5.1)].
- With a known hypersensitivity reaction to VIBERZI [see Warnings and Precautions ( 5.3)].
- With severe hepatic impairment (Child-Pugh Class C). These patients are at risk for significantly increased plasma concentrations of eluxadoline [see Use in Specific Populations ( 8.6)]
- With a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction. These patients may be at risk for severe complications of bowel obstruction [see Warnings and Precautions ( 5.4)].
5.1 Pancreatitis
Pancreatitis, with or without sphincter of Oddi spasm [see Warnings and Precautions ( 5.1)], has been reported in patients taking either the 75 mg or 100 mg dosage of VIBERZI, including serious cases resulting in hospitalization, primarily in patients without a gallbladder. Fatal cases have also been reported in patients without a gallbladder. VIBERZI is contraindicated in patients without a gallbladder [see Contraindications ( 4)]. Most of the reported cases of serious pancreatitis occurred within a week of starting treatment with VIBERZI and some developed symptoms after one to two doses.
In patients with a gallbladder, evaluate a patient’s alcohol intake prior to starting VIBERZI. Instruct patients to avoid chronic or acute excessive alcohol use while taking VIBERZI. Monitor for new or worsening abdominal pain that may radiate to the back or shoulder, with or without nausea and vomiting. Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of pancreatitis such as acute abdominal or epigastric pain radiating to the back or shoulder associated with elevations of pancreatic enzymes with or without nausea and vomiting [see Contraindications ( 4)].
5.2 Sphincter of Oddi Spasm
There is a risk of sphincter of Oddi spasm, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain (e.g., biliary-type pain) in patients taking VIBERZI [see Adverse Reactions ( 6.1)]. Postmarketing serious adverse reactions of sphincter of Oddi spasm with or without pancreatitis resulting in hospitalization have been reported, primarily in patients without a gallbladder [see Warnings and Precautions ( 5.1)]. Most of the reported cases of serious sphincter of Oddi spasm occurred within a week of starting treatment with VIBERZI and some developed symptoms after one to two doses. VIBERZI is contraindicated in patients without a gallbladder [see Contraindications ( 4)].
Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of sphincter of Oddi spasm such as acute worsening of abdominal pain, (e.g. acute epigastric or biliary [i.e., right upper quadrant] pain), that may radiate to the back or shoulder with or without nausea and vomiting, associated with elevations of pancreatic enzymes or liver transaminases. Do not restart VIBERZI in patients who developed biliary duct obstruction or sphincter of Oddi spasm while taking VIBERZI [see Contraindications ( 4)].
5.3 Hypersensitivity Reactions
In postmarketing experience, serious hypersensitivity reactions (including anaphylaxis) have been reported following VIBERZI administration. Some of these reactions occurred after the first one or two doses of VIBERZI [see Adverse Reactions ( 6.2)].
Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of a hypersensitivity reaction [see Contraindications ( 4)].
5.4 Constipation
Constipation, sometimes requiring hospitalization, has been reported following VIBERZI administration. In postmarketing experience, severe cases with development of intestinal obstruction, intestinal perforation, and fecal impaction, requiring intervention, have also been reported. Instruct patients to stop VIBERZI and immediately contact their healthcare provider if they experience severe constipation. Avoid use with other drugs that may cause constipation [see Adverse Reactions ( 6.1), Drug Interactions ( 7)].