Eluxadoline

Eluxadoline is an Opiate receptor agonist belonging to a Gastrointestinal agent.

Eluxadoline is a mixed mu-opioid receptor agonist used to treat irritable bowel syndrome with diarrhea.

The absolute bioavailability of Eluxadoline has not been determined. The plasma protein binding of Eluxadoline was 81%. The metabolism of Eluxadoline is not clearly established. There is evidence that glucuronidation can occur to form an acyl glucuronide metabolite. Following a single oral dose of 300 mg [14C] Eluxadoline in healthy male subjects, 82.2% of the total radioactivity was recovered in feces within 336 hours and less than 1% was recovered in urine within 192 hours.

Eluxadoline shows side effects like Nausea, vomiting, etc.

Eluxadoline is available in the form of Oral tablets.

Eluxadoline is available in India, the US, Europe, Canada, China, Japan, France, Spain, and Australia.

Eluxadoline belongs to the Gastrointestinal agent and acts as an Opiate receptor agonist.

Eluxadoline is a mu-opioid receptor agonist, kappa opioid receptor agonist, and delta-opioid receptor antagonist. Eluxadoline is used for diarrhea-predominant IBS because it reduces intestinal contractility and normalizes stress-induced acceleration of upper GI transit. Antagonistic activity at the delta receptor minimizes the constipating effect usually seen by mu-opioid receptor agonists alone. Because of its limited systemic bioavailability, there may be fewer side effects associated with the use of Eluxadoline in comparison with other therapies used to treat diarrhea-predominant IBS.

The Data on the Onset and Duration of action of Eluxadoline is not clinically established.

The Tmax of Eluxadoline is 1.5 hours.

Eluxadoline is a mixed mu-opioid receptor agonist used to treat irritable bowel syndrome with diarrhea.

Eluxadoline is approved for use in the following clinical indications

• Irritable bowel syndrome with diarrhea

Eluxadoline is a mixed mu-opioid receptor agonist used to treat irritable bowel syndrome with diarrhea.

• Irritable bowel syndrome with diarrhea

Oral: Initial: 100 mg twice daily; decrease to 75 mg twice daily in patients who experience intolerance (eg, constipation, nausea). If no improvement in symptoms by 1 month, consider discontinuation.

Eluxadoline is available in various strengths as 75mg and 100mg.

Eluxadoline is available in the form of an Oral Tablet.

• Dosage Adjustment in Kidney Patient

eGFR ≥60 mL/minute/1.73 m²: No dosage adjustment necessary.

eGFR <60 mL/minute/1.73 m²: 75 mg twice daily.

eGFR <15 mL/minute/1.73 m² (end-stage renal disease not yet requiring dialysis): 75 mg twice daily.

• Dosage Adjustment in Hepatic impairment Patient

Mild (Child-Pugh class A) to moderate (Child-Pugh class B) impairment: 75 mg twice daily.

Severe impairment (Child-Pugh class C): Use is contraindicated.

Eluxadoline is contraindicated in patients with

• Without a gallbladder. These patients are at increased risk of developing serious adverse reactions of pancreatitis and/or sphincter of Oddi spasm.
• 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.
• 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.
• 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.
• With a known hypersensitivity reaction to eluxadoline.
• With severe hepatic impairment (Child-Pugh Class C). These patients are at risk for significantly increased plasma concentrations of Eluxadoline.
• 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.

• Constipation

Constipation, sometimes requiring hospitalization, has been reported; severe cases with intestinal obstruction, intestinal perforation, and fecal impaction requiring intervention may also occur. Discontinue use immediately if severe constipation occurs; avoid concomitant use with drugs that may cause constipation.

• Hypersensitivity reactions:

Severe hypersensitivity reactions, including anaphylaxis, have been reported during post-marketing surveillance. Some reactions occurred following the first or second dose. Discontinue immediately in patients who develop signs or symptoms of a hypersensitivity reaction.

• Pancreatitis:

May cause pancreatitis, with or without sphincter of Oddi spasm, including serious cases (some fatal) requiring hospitalization. Primarily occurs in patients without a gallbladder (use is contraindicated). Most reported serious pancreatitis cases occurred within a week of starting treatment; some developed after 1 or 2 doses. Avoid chronic or acute excessive alcohol use during therapy. Monitor for signs and symptoms of pancreatitis; discontinue use if new or worsening abdominal pain that may radiate to the back or shoulder (with or without nausea/vomiting) develops.

• Sphincter of Oddi spasm

May cause sphincter of Oddi spasm resulting in pancreatitis or elevated hepatic enzymes; most reported serious cases occurred during the first week of treatment, while some developed symptoms after 1 or 2 doses. Discontinue use if patients experience symptoms of sphincter of Oddi spasm such as acute worsening of epigastric- or biliary-type abdominal pain (eg, right upper quadrant pain) that may radiate to the back or shoulder with or without nausea/vomiting, associated with elevations of pancreatic enzymes or hepatic transaminases. Permanently discontinue use in patients who develop biliary duct obstruction or sphincter of Oddi spasm.

• Hepatic impairment:

Plasma concentrations are increased in patients with hepatic impairment; contraindicated in patients with severe hepatic impairment. Use with caution in patients with mild to moderate hepatic impairment; dosage adjustment is required.

• Renal impairment:

Use with caution in patients with moderate to severe renal impairment; dosage adjustment is required.

• Abuse potential

Current data suggest that eluxadoline has some potential for drug abuse and psychological dependence. Naloxone should be considered in the event of overdose.

Avoid the consumption of alcohol, it may increase the risk of pancreatitis.

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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Eluxadoline and any potential adverse effects on the breastfed infant from Eluxadoline or from the underlying maternal condition.

Adverse events have not been observed in animal reproduction studies.

Common

● Dizziness, fatigue, drowsiness, euphoria, intoxicated feeling, sedation, Skin rash Constipation, nausea, abdominal pain, vomiting, abdominal distention, flatulence, viral gastroenteritis, gastroesophageal reflux disease, Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Upper respiratory tract infection, nasopharyngitis, bronchitis, asthma, bronchospasm, respiratory failure, increased bronchial secretions.

Rare

● Anaphylaxis, angioedema, chest pain, chest tightness, dyspnea, fecal impaction, hypersensitivity reaction, intestinal obstruction, intestinal perforation, pancreatitis, pharyngeal edema, spasm of the sphincter of Oddi.

• Drugs that Cause Constipation

Increased risk for constipation-related adverse reactions and potential for constipation-related serious adverse reactions. Avoid use with other drugs that may cause constipation (see below); loperamide may be used occasionally for acute management of severe diarrhea but avoid chronic use. Discontinue loperamide immediately if constipation occurs. (alosetron, anticholinergics, opioids)

• Breast cancer resistance protein (BCRP) substrate

Eluxadoline may increase the exposure of co-administered Breast cancer resistance protein (BCRP) substrates. Increased exposure to rosuvastatin when co-administered with Eluxadoline with a potential for increased risk of myopathy/rhabdomyolysis. Use the lowest effective dose of rosuvastatin.

• CYP3A Substrates with Narrow Therapeutic Index

Potential for increased exposure of co-administered drug Monitor drug concentrations or other pharmacodynamic markers of drug effect when concomitant use with eluxadoline is initiated or discontinued (alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).

The common side effects of Eluxadoline include the following

Common side effects

● Nausea, vomiting.

Rare side effects

● Pain that begins in the upper stomach area but may spread to the back or shoulder with or without nausea and vomiting, Severe constipation, Rash, Hives, Swollen face or throat, Shortness of breath, Throat tightness, Chest pain or tightness, or difficulty swallowing or breathing.

• Pregnancy

Pregnancy Category

There are no studies with Eluxadoline 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.

• Nursing Mothers

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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Eluxadoline and any potential adverse effects on the breastfed infant from Eluxadoline or from the underlying maternal condition.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

Of 1795 IBS-D patients in clinical trials of Eluxadoline 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%).

Pharmacodynamic

Information is not available.

Pharmacokinetics

• Absorption

Absolute bioavailability of eluxadoline has not been determined.

• Distribution

Plasma protein binding of eluxadoline was 81%.

• Metabolism and Excretion

Metabolism of eluxadoline is not clearly established. There is evidence that glucuronidation can occur to form an acyl glucuronide metabolite. Following a single oral dose of 300 mg [14C] eluxadoline in healthy male subjects, 82.2% of the total radioactivity was recovered in feces within 336 hours and less than 1% was recovered in urine within 192 hours

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206940s003lbl.pdf
• https://medlineplus.gov/druginfo/meds/a615054.html
• https://www.rxlist.com/viberzi-drug.htm#warnings
• https://reference.medscape.com/drug/viberzi-eluxadoline-1000018
• https://www.drugs.com/mtm/eluxadoline.html
• https://go.drugbank.com/drugs/DB09272
• https://www.uptodate.com/contents/eluxadoline-drug-information#F28617129