eluxadoline

This drug is contraindicated in case of having:

• Blockage of the gallbladder or a sphincter of Oddi problem
• Problems with excessive alcohol use
• Pancreatitis
• Liver problems
• Chronic or severe constipation{{cite web | title=Eluxadoline Monograph for Professionals | website=Drugs.com | date=10 May 2024 | url=https://www.drugs.com/monograph/eluxadoline.html | access-date=11 November 2024}}

Common adverse effects are constipation and nausea, but rates of discontinuation due to constipation were low for both eluxadoline and placebo. Rare adverse effects: fatigue, bronchitis, viral gastroenteritis.

Rare serious adverse effects include pancreatitis with a general incidence of 0.3%: higher incidence with 100 mg dose (0.3%) than with 75 mg dose (0.2%).{{cite journal | vauthors = Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS | s2cid = 205098220 | display-authors = 6 | title = Eluxadoline for Irritable Bowel Syndrome with Diarrhea | journal = The New England Journal of Medicine | volume = 374 | issue = 3 | pages = 242–53 | date = January 2016 | pmid = 26789872 | doi = 10.1056/NEJMoa1505180 | doi-access =free }} The risk is even greater in those who do not have a gallbladder and the medication is not recommended in this group.{{cite web |author = Office of the Commissioner |title=Safety Alerts for Human Medical Products - Viberzi (eluxadoline): Drug Safety Communication - Increased Risk of Serious Pancreatitis In Patients Without A Gallbladder|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm546771.htm|website=www.fda.gov|access-date=19 March 2017 |date=15 March 2017|archive-url=https://web.archive.org/web/20180425032716/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm546771.htm|archive-date=25 April 2018}}

In March 2017, the U.S. Food and Drug Administration issued a safety alert for eluxadoline concerning an increased risk of serious pancreatitis in patients without a gallbladder.{{Cite web|url=http://www.medscape.com/viewarticle/877264|title=FDA: Avoid IBS Drug Viberzi in Patients With No Gallbladder|last=Brooks|first=Megan | name-list-style = vanc |date=March 2017|website=www.medscape.com|access-date=2017-09-18}} An FDA review found that in such patients, spasm of the sphincter of Oddi may lead to severe pancreatitis.{{cite web |url= https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm546771.htm?source=govdelivery |title=Safety Alerts for Human Medical Products - Viberzi (eluxadoline): Drug Safety Communication - Increased Risk of Serious Pancreatitis In Patients Without A Gallbladder |author = Office of the Commissioner |website=www.fda.gov|language=en|access-date=2017-09-18}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} The FDA reported that in some cases symptoms have occurred with just one or two doses at the recommended dosage for patients without a gallbladder (75 mg). Of two deaths associated with eluxadoline reported up to February 2017, both occurred in patients without a gallbladder.

Elevated concentrations of eluxadoline were observed with co-administration of inhibitors of the transporter protein OATP1B1, such as ciclosporin, gemfibrozil, certain antiretrovirals, rifampicin, and eltrombopag.{{medcn|date=November 2024}}

Concurrent use of other drugs that cause constipation, such as opioids, alosetron, anticholinergics, and bismuth subsalicylate, is not preferred.{{Cite web|title = bismuth subsalicylate|url = https://reference.medscape.com/drug/kaopectate-pepto-bismol-bismuth-subsalicylate-342037|website = Medscape |access-date = 2016-05-10}}

Eluxadoline increases the concentrations of drugs which are OATP1B1 and BCRP substrates.{{medcn|date=November 2024}} Co-administration of eluxadoline with rosuvastatin may increase the risk of rhabdomyolysis.

Eluxadoline is a μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist{{cite journal | vauthors = Levy-Cooperman N, McIntyre G, Bonifacio L, McDonnell M, Davenport JM, Covington PS, Dove LS, Sellers EM | display-authors = 6 | title = Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 359 | issue = 3 | pages = 471–481 | date = December 2016 | pmid = 27647873 | pmc = 5118645 | doi = 10.1124/jpet.116.236547 }} that acts locally in the enteric nervous system, possibly decreasing adverse effects on the central nervous system.{{Cite web|title = Actavis Announces FDA Acceptance for Filing of NDA for Eluxadoline|url = https://www.drugs.com/nda/eluxadoline_140902.html|website = www.drugs.com|access-date = 2015-06-01}}{{Cite web|title = FDA Approves Viberzi (eluxadoline) for Irritable Bowel Syndrome with Diarrhea (IBS-D) in Adults|url = https://www.drugs.com/newdrugs/fda-approves-viberzi-eluxadoline-irritable-bowel-syndrome-diarrhea-ibs-d-adults-4217.html|website = www.drugs.com|access-date = 2015-06-01}}

In the in vitro studies, eluxadoline was found to be transported by OAT3 (SLC22A8), OATP1B1 (SLCO1B1), and BSEP (ABCB11) at the highest concentrations tested (400 ng/ml, which is 162-fold larger than the observed C_max of the highest therapeutic dose of 100 mg). However, it was not to be transported by OCT1 POU2F1, OAT1 (organic anion transporter 1), OCT2, OATP1B3 (SLCO1B3), P-gp (P-glycoprotein), or BCRP (ABCG2).

Multidrug resistance-associated protein 2 (MRP2)-vesicular accumulation of eluxadoline was observed, indicating that the drug is a substrate of MRP2. Eluxadoline was not found to inhibit BCRP-, BSEP-, MRP2-, OCT1-, OCT2-, OAT1-, OAT3-, or OATP1B3-mediated transport of probe substrates but inhibited the transport of probe substrates of OATP1B1 and P-gp. In the in vitro studies, it was observed that eluxadoline is an in vivo substrate of OATP1B1, OAT3, and MRP2. Finally, no inhibition or induction of cytochrome P450 enzymes was observed.{{cite journal | vauthors = Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J | title = Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline | journal = Journal of Clinical Pharmacology | volume = 55 | issue = 5 | pages = 534–42 | date = May 2015 | pmid = 25491493 | pmc = 4402028 | doi = 10.1002/jcph.442 }}

Following a 100 mg dose of eluxadoline, the C_max was about 2 to 4 ng/ml and AUC was 12 to 22 ng.h/ml. Eluxadoline has linear pharmacokinetics with no accumulation upon repeated twice daily dosing. Taking eluxadoline with high fat meal decreased the C_max by 50% and AUC by 60%.

The synthesis of eluxadoline was published in 2006.[https://patents.google.com/patent/WO2006099060A2/en], Process of the Preparation of Opioid modulators.

{{Reflist}}

{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}

{{Drugs for functional gastrointestinal disorders}}

{{Opioidergics}}

{{Irritable bowel syndrome}}

Category:Amines

Category:Antidiarrhoeals

Category:Carbamates

Category:Delta-opioid receptor antagonists

Category:Diarrhea

Category:Imidazoles

Category:Drugs developed by AbbVie

Category:Janssen Pharmaceutica

Category:Kappa-opioid receptor agonists

Category:Mu-opioid receptor agonists

Category:Peripherally selective drugs