Viberzi

Peripheral Mu Opioid Receptor Agonists for IBS-D

Administer the tablets with food.
Missed dose: Skip the missed dose, and administer the next scheduled dose at the usual time.

bronchospasm / Rapid / 3.0-3.0
constipation / Delayed / 0-1.0
pancreatitis / Delayed / 0.3-0.3
GI perforation / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

impaired cognition / Early / 0-2.0
euphoria / Early / 0-2.0
wheezing / Rapid / 0-2.0
elevated hepatic enzymes / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
dyspnea / Early / Incidence not known
respiratory depression / Rapid / Incidence not known

nausea / Early / 7.0-8.0
abdominal pain / Early / 6.0-7.0
infection / Delayed / 3.0-5.0
vomiting / Early / 4.0-4.0
pharyngitis / Delayed / 3.0-4.0
flatulence / Early / 3.0-3.0
fatigue / Early / 3.0-3.0
dizziness / Early / 3.0-3.0
rash / Early / 3.0-3.0
gastroesophageal reflux / Delayed / 0-2.0
drowsiness / Early / 0-2.0
maculopapular rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known

Viberzi

Rx, schedule IV

Oral mu and kappa opioid receptor agonist and delta opioid receptor antagonist
Indicated for use in adults to treat irritable bowel syndrome with diarrhea (IBS-D)
Stop treatment if severe constipation lasting more than 4 days develops

100 mg PO twice daily. Reduce dose to 75 mg PO twice daily in persons unable to tolerate higher dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Discontinue treatment in persons who develop severe constipation.

Mild to moderate hepatic impairment (Child-Pugh Class A and B, score 9 or less): The recommended dose is 75 mg PO twice daily with food.
Severe hepatic impairment (Child-Pugh Class C, score more than 9): Use is contraindicated.

eGFR 60 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR less than 60 mL/minute/1.73 m2: The recommended dose is 75 mg PO twice daily with food.
eGFR less than 15 mL/minute/1.73 m2 [includes those with end-stage renal disease (ESRD) not yet on dialysis]: 75 mg PO twice daily with food.

Acetaminophen; Caffeine; Dihydrocodeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together. Additionally, concomitant use of dihydrocodeine with eluxadoline may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of eluxadoline could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If eluxadoline is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Eluxadoline is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Acetaminophen; Hydrocodone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of eluxadoline is necessary. If eluxadoline is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like eluxadoline can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If eluxadoline is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Alfentanil: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as alfentanil. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Alosetron: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as alosetron. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Consider a reduction of the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with clarithromycin. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and clarithromycin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Anticholinergics: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of eluxadoline is necessary. If eluxadoline is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like eluxadoline can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If eluxadoline is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Major) When administered concurrently with atazanavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Atazanavir; Cobicistat: (Major) When administered concurrently with atazanavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); atazanavir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. (Major) When administered concurrently with cobicistat, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cobicistat is an OATP1B1/1B3 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with eluxadoline. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and eluxadoline is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atropine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Atropine; Difenoxin: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Belladonna; Opium: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days. (Major) Avoid use of eluxadoline with medications that may cause constipation, such as opium. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with eluxadoline may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of eluxadoline in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If eluxadoline is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Eluxadoline is a weak inhibitor of CYP3A4.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Benztropine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking eluxadoline. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a BCRP substrate and eluxadoline is a BCRP inhibitor. Coadministration with another BCRP inhibitor increased berotralstat exposure by 69%.
Brincidofovir: (Moderate) Postpone the administration of eluxadoline for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and eluxadoline is necessary. Brincidofovir is an OATP1B1 substrate and eluxadoline is an OATP1B1 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1 inhibitor.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Ceritinib: (Moderate) Monitor for an increase in eluxadoline-related adverse reactions including impaired mental or physical abilities if coadministration with ceritinib is necessary. The metabolism of eluxadoline by CYP pathways has not been clearly established, but strong CYP inhibitors such as ceritinib have the potential to increase eluxadoline exposure.
Chlordiazepoxide; Clidinium: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Chlorpheniramine; Codeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together. Additionally, concomitant use of dihydrocodeine with eluxadoline may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of eluxadoline could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If eluxadoline is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Eluxadoline is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Clarithromycin: (Major) Consider a reduction of the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with clarithromycin. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and clarithromycin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Cobicistat: (Major) When administered concurrently with cobicistat, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cobicistat is an OATP1B1/1B3 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Codeine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Codeine; Guaifenesin: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Codeine; Phenylephrine; Promethazine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Codeine; Promethazine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Cyclosporine: (Major) When administered concurrently with cyclosporine, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cyclosporine is an OATP inhibitor. Use of these drugs together results in a 4.4-fold increase in exposure (AUC) and a 6.2-fold increase in maximum plasma concentration of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Daclatasvir: (Major) Consider a reduction in the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with daclatasvir. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and daclatasvir is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Darolutamide: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with darolutamide. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and darolutamide is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Darunavir; Cobicistat: (Major) When administered concurrently with cobicistat, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cobicistat is an OATP1B1/1B3 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) When administered concurrently with cobicistat, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cobicistat is an OATP1B1/1B3 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Dicyclomine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Diphenoxylate; Atropine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Elagolix: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as eluxadoline is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of OATP1B1. Eluxadoline inhibits OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as eluxadoline is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of OATP1B1. Eluxadoline inhibits OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elexacaftor; tezacaftor; ivacaftor: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with elexacaftor. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and elexacaftor is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of eluxadoline and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of eluxadoline and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Eluxadoline is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 inhibitors, such as eluxadoline, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Eltrombopag: (Major) When administered concurrently with eltrombopag, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); eltrombopag is an in vitro inhibitor of OATP1B1. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) When administered concurrently with cobicistat, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cobicistat is an OATP1B1/1B3 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) When administered concurrently with cobicistat, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); cobicistat is an OATP1B1/1B3 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Enasidenib: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with enasidenib. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and enasidenib is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Encorafenib: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with encorafenib. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and encorafenib is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Erythromycin: (Major) Consider reduction of the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with erythromycin. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and erythromycin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Fentanyl: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as fentanyl. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Flavoxate: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Gemfibrozil: (Major) When administered concurrently with gemfibrozil, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); gemfibrozil is an OATP1B1/2B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Glecaprevir; Pibrentasvir: (Major) Reduce the dose of eluxadoline to 75 mg PO twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with glecaprevir. Advise patients against driving or operating machinery until the combined effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); glecaprevir is an OATP1B1/1B3 inhibitor. This specific interaction has not been evaluated; however, administration of eluxadoline with another OATP inhibitor resulted in elevated exposure (AUC) and maximum plasma concentration of eluxadoline by 4.4- and 6.2-fold, respectively. (Major) Reduce the dose of eluxadoline to 75 mg PO twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with pibrentasvir. Advise patients against driving or operating machinery until the combined effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); pibrentasvir is an OATP1B1/1B3 inhibitor. This specific interaction has not been evaluated; however, administration of eluxadoline with another OATP inhibitor resulted in elevated exposure (AUC) and maximum plasma concentration of eluxadoline by 4.4- and 6.2-fold, respectively.
Glycopyrrolate: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Glycopyrrolate; Formoterol: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Guaifenesin; Hydrocodone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Homatropine; Hydrocodone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days. (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Hydrocodone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Hydrocodone; Ibuprofen: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Hydrocodone; Pseudoephedrine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Hydromorphone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as hydromorphone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Hyoscyamine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of eluxadoline is necessary. If eluxadoline is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like eluxadoline can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If eluxadoline is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Indacaterol; Glycopyrrolate: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) When administered concurrently with rifampin, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); rifampin is an inhibitor of OATP. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Isoniazid, INH; Rifampin: (Major) When administered concurrently with rifampin, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); rifampin is an inhibitor of OATP. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Consider a reduction of the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with clarithromycin. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and clarithromycin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Leflunomide: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with leflunomide. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and leflunomide is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with eluxadoline as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; eluxadoline is reported to be a weak CYP3A4 inhibitor, but clinically relevant drug-drug interactions with eluxadoline are not certain. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Leniolisib: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with leniolisib. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and leniolisib is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Letermovir: (Moderate) Concurrent administration of eluxadoline and letermovir may increase the plasma concentration of both drugs. In patients receiving both letermovir and cyclosporine, administer eluxadoline at a dose of 75 mg twice daily, because cyclosporine increases the inhibitory potential of letermovir. If these drugs are given together, closely monitor for adverse events including impaired mental or physical abilities, tachycardia, atrial fibrillation, and gastrointestinal events. Both eluxadoline and letermovir are substrates and inhibitors of the organic anion-transporting polypeptide (OATP1B1).
Levorphanol: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as levorphanol. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Lopinavir; Ritonavir: (Major) When administered concurrently with lopinavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); lopinavir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. (Major) When administered concurrently with ritonavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); ritonavir is an OATP1B1 inhibitor.
Meperidine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as meperidine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Methadone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as methadone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Methscopolamine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Midostaurin: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with midostaurin. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and midostaurin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Morphine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as morphine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Morphine; Naltrexone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as morphine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Neostigmine; Glycopyrrolate: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Nirmatrelvir; Ritonavir: (Major) When administered concurrently with ritonavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); ritonavir is an OATP1B1 inhibitor.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with eluxadoline due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and eluxadoline is a weak CYP3A4 inhibitor.
Oxybutynin: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of eluxadoline is necessary. If eluxadoline is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like eluxadoline can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If eluxadoline is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Oxymorphone: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as oxymorphone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Pramlintide: (Major) Due to its effects on gastric emptying, pramlintide should not be considered for patients taking medications that alter gastrointestinal motility (e.g., slow GI motility, such as eluxadoline). Consider alternative diabetic treatments. Patients using these medications have not been studied in pramlintide clinical trials. Severe constipation, which could result in bowel blockage, is a potential concern.
Probenecid: (Minor) Systemic exposure (AUC) and maximum plasma concentration of eluxadoline are increased by 35% and 31%, respectively, when administered concurrently with probenecid. According to the manufacturer, the increase in exposure is not expected to be clinically meaningful; no dosage adjustments are required during coadministration with probenecid.
Probenecid; Colchicine: (Minor) Systemic exposure (AUC) and maximum plasma concentration of eluxadoline are increased by 35% and 31%, respectively, when administered concurrently with probenecid. According to the manufacturer, the increase in exposure is not expected to be clinically meaningful; no dosage adjustments are required during coadministration with probenecid.
Propantheline: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Remifentanil: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as remifentanil. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together.
Ribociclib: (Moderate) Monitor for an increase in eluxadoline-related adverse reactions including impaired mental or physical abilities if coadministration with ribociclib is necessary. The metabolism of eluxadoline by CYP pathways has not been clearly established, but strong CYP inhibitors such as ribociclib have the potential to increase eluxadoline exposure.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in eluxadoline-related adverse reactions including impaired mental or physical abilities if coadministration with ribociclib is necessary. The metabolism of eluxadoline by CYP pathways has not been clearly established, but strong CYP inhibitors such as ribociclib have the potential to increase eluxadoline exposure.
Rifampin: (Major) When administered concurrently with rifampin, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); rifampin is an inhibitor of OATP. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Ritonavir: (Major) When administered concurrently with ritonavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); ritonavir is an OATP1B1 inhibitor.
Rosuvastatin: (Moderate) Close monitoring for adverse effects, such as rhabdomyolysis and myopathy, is advised when eluxadoline is administered concurrently with rosuvastatin. Eluxadoline is an inhibitor of the organic anion-transporting peptide (OATP1B1) and the breast cancer resistance protein (BCRP); rosuvastatin is a substrate of both transporters. Use of these drugs together results in a 40% increase in the exposure (AUC) and a 18% increase in the maximum plasma concentration (Cmax) of rosuvastatin. Administer the lowest effect rosuvastatin dose and monitor for adverse effects.
Rosuvastatin; Ezetimibe: (Moderate) Close monitoring for adverse effects, such as rhabdomyolysis and myopathy, is advised when eluxadoline is administered concurrently with rosuvastatin. Eluxadoline is an inhibitor of the organic anion-transporting peptide (OATP1B1) and the breast cancer resistance protein (BCRP); rosuvastatin is a substrate of both transporters. Use of these drugs together results in a 40% increase in the exposure (AUC) and a 18% increase in the maximum plasma concentration (Cmax) of rosuvastatin. Administer the lowest effect rosuvastatin dose and monitor for adverse effects.
Saquinavir: (Major) When administered concurrently with saquinavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); saquinavir is an OATP1B1 inhibitor.
Scopolamine: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Sofosbuvir; Velpatasvir: (Major) When administered concurrently with velpatasvir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); velpatasvir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) When administered concurrently with velpatasvir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); velpatasvir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. (Major) When administered concurrently with voxilaprevir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); voxilaprevir is an OATP1B1 inhibitor. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if eluxadoline must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of eluxadoline is necessary. If eluxadoline is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like eluxadoline can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If eluxadoline is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of eluxadoline is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and eluxadoline is a BCRP inhibitor.
Teriflunomide: (Major) When administered concurrently with teriflunomide, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); teriflunomide is an in vitro inhibitor of OATP.
Tipranavir: (Major) When administered concurrently with tipranavir, the dose of eluxadoline must be reduced to 75 mg PO twice daily, and the patient should be closely monitored for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity). Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is a substrate of the organic anion-transporting peptide (OATP1B1); tipranavir is an OATP1B1 inhibitor.
Trihexyphenidyl: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
Trofinetide: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with trofinetide. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and trofinetide is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Voclosporin: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with voclosporin. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and voclosporin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Consider a reduction of the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects (i.e., decreased mental and physical acuity) if coadministered with clarithromycin. Coadministration may increase exposure of eluxadoline. Advise patients against driving or operating machinery until the combine effects of these drugs on the individual patient is known. Eluxadoline is an OATP1B1 substrate and clarithromycin is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.

Viberzi Oral Tab: 75mg, 100mg

200 mg/day PO.

200 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Eluxadoline is an agonist of the mu and kappa opioid receptors and an antagonist of the delta opioid receptor. The binding affinities (Ki) to human mu and delta opioid receptors are 1.8 nM and 430 nM, respectively. The Ki for human kappa opioid receptors has not been determined. When opioid receptors agonists, such as eluxadoline, interact with receptors located in the gastrointestinal tract, secretions from the stomach, pancreas, and biliary tract are decreased. The combination of effects of opiate agonists on the GI tract results in constipation and delayed digestion.

Eluxadoline is administered via the oral route. Following systemic absorption, the drug is 81% bound to human plasma proteins. The pathway by which the drug is metabolized has not been established; however, evidence suggests it may undergo glucuronidation resulting in an acyl glucuronide metabolite. The mean plasma elimination half-life ranges from 3.7 hours to 6 hours. Excretion occurs primarily through the feces, with 82.2% of an administered dose recovered within 336 hours; less than 1% is recovered in the urine after 192 hours.
 
Affected cytochrome P450 isoenzymes and transporters: Bile salt export pump (BSEP), multidrug resistance-associated protein (MRP2), organic anion transporter (OAT3), organic anion-transporting polyprotein (OATP1B1)
In vitro studies indicate that eluxadoline is neither an inducer of CYP1A2, CYP2C9, CYP2C19, and CYP3A4, nor an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP2D6 at clinically relevant systemic concentrations. Although CYP2E1 was slightly inhibited by eluxadoline, clinically meaningful interactions are unlikely. Despite mechanism-based inhibition of CYP3A4 in vitro, eluxadoline did not have a clinically meaningful drug-drug interaction with the CYP3A4 substrate midazolam. In vitro studies suggest eluxadoline is a substrate for the transporters OAT3, OATP1B1, BSEP, and MRP2, but not for OCT1, OCT2, OAT1, OATP1B3, P-gp and BCRP. Based on in vitro studies, clinically meaningful interaction via inhibition of OCT1, OCT2, OAT2, OAT3, OATP1B3, BSEP and MRP2 by eluxadoline is unlikely. Cytochrome P450 and UGT pathways have minimal involvement in the metabolism of eluxadoline. It is unlikely that metabolism of eluxadoline by these enzymes has a clinically meaningful impact on systemic exposure.

Following oral administration, eluxadoline displays linear pharmacokinetics with no accumulation resulting from repeated twice daily dosing. However, the pharmacokinetic parameters of eluxadoline are variable. In a study of health volunteers administered 100 mg doses, the maximum plasma concentration (Cmax) ranged from 2 to 4 ng/mL, exposures (AUC) ranged from 12 to 22 ng x h/mL. The time to reach maximum plasma concentrations (Tmax) is also variable. Under fed conditions, the median Tmax was 1.5 hours (range: 1 to 8 hours). When given with food, the median Tmax was 2 hours (range: 0.5 to 6 hours). Administering eluxadoline with a high-fat meal (800 to 1000 calories, 50% from fat) decreases the Cmax by 50% and the AUC by 60%. The absolute bioavailability has not been determined.

There are no studies with eluxadoline during human pregnancy that inform any drug-associated risks. In animal studies, no teratogenic effects were observed in rats or rabbits administered oral and subcutaneous doses approximately 51 and 115 times the human exposure, respectively. 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.

No data are available regarding the presence of eluxadoline in human milk, the effects of eluxadoline on the breast-fed infant, or the effects of eluxadoline on milk production. However, eluxadoline is present in rat milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition in the mother.