Lotronex

Serotonin Receptor Antagonists for IBS-D

 
NOTE: Some patients may experience constipation. Do not initiate alosetron in patients who are currently constipated. Discontinue the drug immediately if constipation or signs of ischemic colitis develop. Re-contact the prescriber if constipation is not resolved after stopping the drug. Do not restart treatment in patients who develop ischemic colitis.

Oral Administration

May be administered with or without food; swallow each tablet with a full glass of water.

Severe

GI bleeding / Delayed / Incidence not known
toxic megacolon / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
ileus / Delayed / Incidence not known
GI obstruction / Delayed / Incidence not known

Moderate

constipation / Delayed / 11.0-29.0
hemorrhoids / Delayed / Incidence not known
colitis / Delayed / Incidence not known

Mild

dyspepsia / Early / Incidence not known
xerostomia / Early / Incidence not known
flatulence / Early / Incidence not known
infection / Delayed / Incidence not known
vomiting / Early / Incidence not known
abdominal pain / Early / Incidence not known
gastroesophageal reflux / Delayed / Incidence not known
nausea / Early / Incidence not known

Bleeding, constipation, Crohn's disease, diverticulitis, GI bleeding, GI disease, GI obstruction, GI perforation, ischemic colitis, thrombophlebitis, toxic megacolon, ulcerative colitis

Alosetron is contraindicated in patients with a history of ischemic colitis. Alosetron should be immediately discontinued in patients who experience severe constipation, bloody diarrhea, rectal bleeding, or a sudden worsening of abdominal pain. Alosetron is also contraindicated in patients with a history of serious GI disease such as GI obstruction, GI perforation, GI stricture, toxic megacolon, and/or GI adhesions. Alosetron is contraindicated in patients with a history of or currently active diverticulitis, Crohn's disease, or ulcerative colitis. Alosetron should not be used in patients who are currently experiencing constipation. In addition, patients with a history of chronic or severe constipation or with a history of sequelae from constipation should not receive alosetron. Alosetron is contraindicated in patients with impaired intestinal circulation, thrombophlebitis or a hypercoagulable state. A Black Box Warning in the Lotronex package insert states that serious GI adverse events, some fatal, have occurred with the use of alosetron. Ischemic colitis and serious complications of constipation have resulted in hospitalization, blood transfusion, surgery and death. Patients taking alosetron should immediately report to their health care professionals symptoms of constipation or ischemic colitis (i.e., rectal bleeding, abrupt abdominal pain, GI bleeding, bloody diarrhea). Alosetron should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Patients who discontinue alosetron, but still have constipation should immediately contact their prescriber. Patients with resolved constipation should not resume alosetron except under the advice of their health care provider. Alosetron should not be resumed in patients who develop ischemic colitis.

Lotronex

Rx

Oral selective serotonin 5-HT3 receptor antagonist
Approved only for adult females with severe diarrhea-predominant IBS (IBS-D) failing conventional therapy
Boxed warning on product label regarding risks for severe constipation and ischemic colitis

For the treatment of severe, chronic, diarrhea-predominant irritable bowel syndrome (IBS) in women for whom conventional therapy has failed.
NOTE: Diarrhea-predominant IBS is considered severe if it includes diarrhea and 1 or more of the following: frequent/severe abdominal pain; frequent bowel urgency or fecal incontinence; restriction of daily activities due to IBS. Anatomic or biochemical GI abnormalities must be excluded prior to prescribing.
NOTE: Safe and effective use in men has not been established. Oral dosage Adult Females

0.5 mg PO twice daily, initially. Hold therapy if constipation occurs; resume at 0.5 mg PO once daily once constipation resolves. May increase the dose up to 1 mg PO twice daily after 4 weeks if lower doses are well tolerated but do not adequately control symptoms. Discontinue therapy if constipation recurs at the lowest dose or if adequate control of symptoms is not achieved after 4 weeks at the maximum dose.

Hepatic Impairment

Alosetron should not be used in patients with severe hepatic impairment (see Contraindications). Use with caution in patients with mild to moderate hepatic impairment, increased systemic exposure is likely to occur and reduced dosages may be advisable, although quantitative guidelines are not available.

Renal Impairment

It is not known if dosage adjustment is required in patients with renal impairment; use with caution.

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Chlorpheniramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Codeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Diphenhydramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Hydrocodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Oxycodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Acrivastine; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Adagrasib: (Moderate) Concomitant use of alosetron with adagrasib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A; adagrasib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A inhibitor increased mean alosetron AUC by 29%.
Alfentanil: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Amantadine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like amantadine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Amitriptyline: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Amoxapine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like amoxapine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant use of alosetron with clarithromycin may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; clarithromycin is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Anticholinergics: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Antidiarrheals: (Moderate) Use alosetron with caution and monitoring in patients taking additional medications that may reduce gastric motility, including antidiarrheals, due to increased risk for serious complications of constipation.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like orphenadrine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Aspirin, ASA; Oxycodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Atazanavir: (Major) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, such as alosetron. Serious drug interactions may occur. If these drugs must be coadministered, monitor patient response and adjust the dose of alosetron if necessary.
Atazanavir; Cobicistat: (Major) Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, such as alosetron. Serious drug interactions may occur. If these drugs must be coadministered, monitor patient response and adjust the dose of alosetron if necessary. (Moderate) Concomitant use of alosetron with cobicistat may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; cobicistat is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Atropine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Atropine; Difenoxin: (Contraindicated) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as antidiarrheals, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Belladonna; Opium: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron. (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Benzhydrocodone; Acetaminophen: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Benztropine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Bethanechol: (Moderate) Pharmacodynamic interactions between alosetron and drugs that enhance peristalsis are theoretically possible, based on opposing pharmacologic outcomes. It may be wise to avoid use of bethanechol during alosetron treatment. Although these potential interactions have not been studied, bethanechol might negate the effect of alosetron.
Brompheniramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Brompheniramine; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Brompheniramine; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Budesonide; Glycopyrrolate; Formoterol: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Buprenorphine: (Moderate) Concurrent use of buprenorphine and antidiarrheals can lead to severe constipation and possibly additive CNS depression.
Buprenorphine; Naloxone: (Moderate) Concurrent use of buprenorphine and antidiarrheals can lead to severe constipation and possibly additive CNS depression.
Bupropion: (Moderate) Alosetron, if used with drugs that have anticholinergic effects such as bupropion, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.
Bupropion; Naltrexone: (Moderate) Alosetron, if used with drugs that have anticholinergic effects such as bupropion, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Capmatinib: (Major) Avoid coadministration of alosetron and capmatinib unless clinically necessary due to the risk of increased plasma concentrations of alosetron. Alosetron is a CYP1A2 substrate and capmatinib is a moderate CYP1A2 inhibitor. Coadministration with a strong CYP1A2 inhibitor increased alosetron exposure by approximately 6-fold and prolonged the half-life by approximately 3-fold. Concomitant use with moderate CYP1A2 inhibitors has not been evaluated, but is expected to have similar potential drug interactions.
Carbamazepine: (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Carbamazepine can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of carbamazepine and alosetron has not been evaluated.
Carbinoxamine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Celecoxib; Tramadol: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Ceritinib: (Moderate) Concomitant use of alosetron with ceritinib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; ceritinib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Chlophedianol; Dexbrompheniramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorcyclizine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlordiazepoxide; Amitriptyline: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlordiazepoxide; Clidinium: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Chlorpheniramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Codeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Dextromethorphan: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Hydrocodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpheniramine; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Chlorpromazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Ciprofloxacin: (Major) Avoid coadministration of alosetron and ciprofloxacin due to the potential for increased exposure and half-life of alosetron. Ciprofloxacin is a strong inhibitor of CYP1A2; alosetron is a CYP1A2 substrate. Coadministration of another strong CYP1A2 inhibitor increased the mean alosetron AUC by about 6-fold and prolonged the half-life by 3-fold.
Cisapride: (Moderate) Pharmacodynamic interactions between alosetron and drugs that enhance peristalsis, such as cisapride, are theoretically possible based on opposing pharmacologic outcomes. It may be wise to avoid use of cisapride concurrently. Although this potential interaction has not been studied, cisapride might negate the effect of alosetron.
Clarithromycin: (Moderate) Concomitant use of alosetron with clarithromycin may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; clarithromycin is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Clemastine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Clomipramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Clozapine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like clozapine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Cobicistat: (Moderate) Concomitant use of alosetron with cobicistat may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; cobicistat is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Codeine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Codeine; Guaifenesin: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Codeine; Phenylephrine; Promethazine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Codeine; Promethazine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Crofelemer: (Contraindicated) Serious and life-threatening constipation and bowel obstruction has been reported in IBS patients taking alosetron in combination with other agents to control diarrhea. The mechanism is pharmacodynamic additive constipation. Patients who have previously been on alosetron should discontinue this medication prior to taking crofelemer.
Cyclizine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Cyclobenzaprine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like cyclobenzaprine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Cyproheptadine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dalfopristin; Quinupristin: (Moderate) Dalfopristin; quinupristin is a major inhibitor of cytochrome P450 3A4 and may decrease the elimination of drugs metabolized by this enzyme including alosetron.
Darunavir: (Major) Caution is warranted when darunavir is administered with alosetron as there is a potential for elevated alosetron concentrations. Alosetron is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4.
Darunavir; Cobicistat: (Major) Caution is warranted when darunavir is administered with alosetron as there is a potential for elevated alosetron concentrations. Alosetron is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. (Moderate) Concomitant use of alosetron with cobicistat may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; cobicistat is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution is warranted when darunavir is administered with alosetron as there is a potential for elevated alosetron concentrations. Alosetron is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. (Moderate) Concomitant use of alosetron with cobicistat may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; cobicistat is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Delavirdine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as alosetron, should be expected with concurrent use of delavirdine.
Desipramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dexamethasone: (Minor) Dexamethasone can induce the activity of CYP3A4 and increase the metabolism of alosetron by increasing the metabolism of the drug, thus potentially reducing the effect of alosetron.
Dexbrompheniramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dexchlorpheniramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dextromethorphan; Bupropion: (Moderate) Alosetron, if used with drugs that have anticholinergic effects such as bupropion, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Dicyclomine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Dimenhydrinate: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Diphenhydramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Diphenhydramine; Ibuprofen: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Diphenhydramine; Naproxen: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Diphenhydramine; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Diphenoxylate; Atropine: (Contraindicated) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as antidiarrheals, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Disopyramide: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like disopyramide, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Doxepin: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Doxylamine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Doxylamine; Pyridoxine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Eluxadoline: (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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Concomitant use of alosetron with cobicistat may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; cobicistat is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of alosetron with cobicistat may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; cobicistat is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Erythromycin: (Moderate) Pharmacodynamic interactions between alosetron and drugs that enhance peristalsis are theoretically possible, based on opposing pharmacologic outcomes. It may be prudent to avoid use of erythromycin (when used to enhance GI motility) during alosetron treatment. Although a potential interaction has not been studied, erythromycin might negate the effect of alosetron. Caution and close monitoring are advised if these drugs are used together.
Fentanyl: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Flavoxate: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Fluphenazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Fluvoxamine: (Contraindicated) The combined use of fluvoxamine and alosetron is contraindicated. Fluvoxamine has been shown to increase mean alosetron plasma concentrations (AUC) approximately 6-fold and prolong the half-life by approximately 3-fold. Elevated serum concentrations of alosetron may result in severe constipation. Fluvoxamine is a strong inhibitor of CYP1A2 and inhibits CYP3A4 and CYP2C9. Alosetron is primarily metabolized by CYP1A2 with minor contributions from CYP3A4 and CYP2C9.
Fosamprenavir: (Moderate) Fosamprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P450 3A4. Although drug interaction studies have not been conducted, the serum concentrations of alosetron may be increased with concomitant administration of fosamprenavir.
Givosiran: (Major) Avoid coadministration of alosetron and givosiran due to the risk of increased alosetron-related adverse reactions. If use is necessary, consider reducing the alosetron dose. Alosetron is a sensitive CYP1A2 substrate. Givosiran may moderately reduce hepatic CYP1A2 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway. Coadministration with a strong CYP1A2 inhibitor increased alosetron exposure by approximately 6-fold and prolonged the half-life by approximately 3-fold. Concomitant use with moderate CYP1A2 inhibitors has not been evaluated, but is expected to have similar potential drug interactions.
Glycopyrrolate: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Glycopyrrolate; Formoterol: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Guaifenesin; Hydrocodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Homatropine; Hydrocodone: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron. (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Hydantoins: (Minor) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of aolsetron, leading to reduced efficacy of alosetron.
Hydralazine: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as hydralazine, however, this interaction has not been studied.
Hydralazine; Isosorbide Dinitrate, ISDN: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as hydralazine, however, this interaction has not been studied.
Hydrocodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Hydrocodone; Ibuprofen: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Hydrocodone; Pseudoephedrine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Hydromorphone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Hydroxyzine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Hyoscyamine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Ibuprofen; Oxycodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Idelalisib: (Moderate) Coadministration of idelalisib and alosetron may increase alosetron concentrations resulting in alosetron-related adverse events. Idelalisib is a strong CYP3A4 inhibitor and alosetron is a CYP3A substrate.
Imipramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Indacaterol; Glycopyrrolate: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Indinavir: (Moderate) Concomitant use of alosetron with indinavir may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; indinavir is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Isoniazid, INH: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as isoniazid, INH, however, this interaction has not been studied.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as isoniazid, INH, however, this interaction has not been studied.
Isoniazid, INH; Rifampin: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as isoniazid, INH, however, this interaction has not been studied.
Itraconazole: (Moderate) Concomitant use of alosetron with itraconazole may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; itraconazole is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Ketoconazole: (Moderate) Concomitant use of alosetron with ketoconazole may increase exposure of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is partially metabolized by CYP3A4; ketoconazole is a strong CY3A4 inhibitor. Coadministration of alosetron with ketoconazole increased mean alosetron expsure (AUC) by 29%.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Concomitant use of alosetron with clarithromycin may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; clarithromycin is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Leflunomide: (Moderate) Closely monitor for reduced efficacy of alosetron if coadministered with leflunomide. An adjustment of the alosetron dose may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. In vivo data suggest that teriflunomide is a weak inducer of CYP1A2. Coadministration of teriflunomide with CYP1A2 substrates, such as alosetron, may decrease alosetron exposure and lead to a reduction in efficacy.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of alosetron is not expected if coadministered with letermovir; however, in patients also receiving cyclosporine, the magnitude of the interaction may be increased. Alosetron is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent administration with another strong CYP3A4 inhibitor increased mean alosetron plasma concentrations (AUC) by 29%.
Levoketoconazole: (Moderate) Concomitant use of alosetron with ketoconazole may increase exposure of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is partially metabolized by CYP3A4; ketoconazole is a strong CY3A4 inhibitor. Coadministration of alosetron with ketoconazole increased mean alosetron expsure (AUC) by 29%.
Levorphanol: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Lonafarnib: (Moderate) Concomitant use of alosetron with lonafarnib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; lonafarnib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Lopinavir; Ritonavir: (Major) Concurrent administration of alosetron with ritonavir may alter alosetron plasma concentrations; however, the precise effect is undefined. Alosetron is metabolized by the hepatic isoenzymes CYP3A4, CYP2C9, and CYP1A2; ritonavir is an inhibitor of CYP3A4 and an inducer of CYP1A2 and possibly CYP2C9. Caution and close monitoring are advised if these drugs are administered together.
Lubiprostone: (Moderate) Alosetron can decrease GI motility and may antagonize the effects of drugs used to treat constipation, such as lubiprostone. In general, it would be illogical to concurrently administer antidiarrheals in combination with lubiprostone. However, lubiprostone may cause diarrhea as a side effect, but drug discontinuation alone may resolve the diarrhea.
Maprotiline: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like maprotiline, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Meclizine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Meperidine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Methadone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Methscopolamine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Metoclopramide: (Moderate) Although a potential interaction has not been studied, metoclopramide might negate the effect of alosetron. Pharmacodynamic interactions between alosetron and drugs that enhance peristalsis are theoretically possible, based on opposing pharmacologic outcomes. It may be prudent to avoid use of metoclopramide during alosetron treatment.
Mexiletine: (Major) Concomitant use of alosetron with mexiletine should be avoided due to the risk for increased alosetron serum concentrations and serious adverse reactions. Alosetron is metabolized by CYP1A2; mexiletine is a moderate inhibitor of this enzyme.
Mitotane: (Moderate) Use caution if mitotane and alosetron are used concomitantly, and monitor for decreased efficacy of alosetron and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and alosetron is a minor (18%) CYP3A4 substrate; coadministration may result in decreased plasma concentrations of alosetron.
Morphine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Morphine; Naltrexone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Nefazodone: (Moderate) Alosetron is partially metabolized by CYP3A4. Nefazodone inhibits this enzyme and may decrease the metabolism of alosetron resulting in increased alosetron plasma concentrations. Coadministration of alosetron with nefazodone has not been studied.
Nelfinavir: (Moderate) Concomitant use of alosetron with nelfinavir may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Alosetron is partially metabolized by hepatic isoenzyme CYP3A4; nelfinavir is a strong inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Neostigmine; Glycopyrrolate: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Netupitant, Fosnetupitant; Palonosetron: (Major) Theoretically, the coadministration of two potent and selective 5HT-3 antagonists, such as palonosetron and alosetron could lead to severe constipation. Constipation, reported individually with alosetron in roughly 25% of patients, could be worsened by the administration of palonosetron, which has a constipation rate of roughly 5% as well as a long half-life. Patients who are debilitated, elderly or taking medications that decrease GI motility may be at greater risk for constipation. Ischemic colitis has been reported in patients receiving alosetron during clinical trials and post-marketing. If a decision is made to co-prescribe palonosetron and alosetron, the patient should be informed of the potential for worsening constipation and should contact their health care provider immediately. If severe constipation or ischemic colitis develops while taking these two drugs, the alosetron should be discontinued immediately and not re-started.
Nirmatrelvir; Ritonavir: (Major) Concurrent administration of alosetron with ritonavir may alter alosetron plasma concentrations; however, the precise effect is undefined. Alosetron is metabolized by the hepatic isoenzymes CYP3A4, CYP2C9, and CYP1A2; ritonavir is an inhibitor of CYP3A4 and an inducer of CYP1A2 and possibly CYP2C9. Caution and close monitoring are advised if these drugs are administered together.
Nortriptyline: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Olanzapine: (Moderate) Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs that have anticholinergic effects such as olanzapine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.

>Olanzapine; Fluoxetine: (Moderate) Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs that have anticholinergic effects such as olanzapine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.
Olanzapine; Samidorphan: (Moderate) Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs that have anticholinergic effects such as olanzapine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid these drugs in patients taking alosetron.
Oliceridine: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Opiate Agonists: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Orphenadrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like orphenadrine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Oxybutynin: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Oxycodone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Oxymorphone: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Palonosetron: (Major) Theoretically, the coadministration of two potent and selective 5HT-3 antagonists, such as palonosetron and alosetron could lead to severe constipation. Constipation, reported individually with alosetron in roughly 25% of patients, could be worsened by the administration of palonosetron, which has a constipation rate of roughly 5% as well as a long half-life. Patients who are debilitated, elderly or taking medications that decrease GI motility may be at greater risk for constipation. Ischemic colitis has been reported in patients receiving alosetron during clinical trials and post-marketing. If a decision is made to co-prescribe palonosetron and alosetron, the patient should be informed of the potential for worsening constipation and should contact their health care provider immediately. If severe constipation or ischemic colitis develops while taking these two drugs, the alosetron should be discontinued immediately and not re-started.
Peginterferon Alfa-2b: (Major) Monitor for adverse effects, such as constipation, associated with increased exposure to alosetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while alosetron is a CYP1A2 substrate.
Perphenazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Perphenazine; Amitriptyline: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Phenobarbital: (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Phenobarbital can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of phenobarbital and alosetron has not been evaluated.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron. (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Phenobarbital can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of phenobarbital and alosetron has not been evaluated.
Phenothiazines: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Posaconazole: (Moderate) Posaconazole and alosetron should be coadministered with caution due to an increased potential for alosetron-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of alosetron. These drugs used in combination may result in elevated alosetron plasma concentrations, causing an increased risk for alosetron-related adverse events.
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 alosetron). 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.
Primidone: (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Primidone, which is metabolized to phenobarbital, can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of these drugs has not been formally evaluated.
Procainamide: (Minor) Alosetron may inhibit the metabolism of drugs metabolized by N-acetyltransferase, such as procainamide, however, this interaction has not been studied.
Prochlorperazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Promethazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Promethazine; Dextromethorphan: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Promethazine; Phenylephrine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Propantheline: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Protriptyline: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Pseudoephedrine; Triprolidine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Pyrilamine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Quinine: (Moderate) Alosetron is metabolized by hepatic cytochrome P450 enzymes. Inhibitors of these enzymes, such as quinine, may decrease the clearance of alosetron and increase the systemic exposure of alosetron. Clinically, increased systemic exposure to alosetron may cause or worsen constipation, which might lead to serious adverse effects.
Remifentanil: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Ribociclib: (Moderate) Concomitant use of alosetron with ribociclib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; ribociclib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Ribociclib; Letrozole: (Moderate) Concomitant use of alosetron with ribociclib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; ribociclib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Ritlecitinib: (Major) Avoid coadministration of alosetron and ritlecitinib unless clinically necessary due to the risk of increased plasma concentrations of alosetron. Alosetron is a CYP1A2 substrate and ritlecitinib is a moderate CYP1A2 inhibitor. Coadministration with a strong CYP1A2 inhibitor increased alosetron exposure by approximately 6-fold and prolonged the half-life by approximately 3-fold. Concomitant use with moderate CYP1A2 inhibitors has not been evaluated, but is expected to have similar potential drug interactions.
Ritonavir: (Major) Concurrent administration of alosetron with ritonavir may alter alosetron plasma concentrations; however, the precise effect is undefined. Alosetron is metabolized by the hepatic isoenzymes CYP3A4, CYP2C9, and CYP1A2; ritonavir is an inhibitor of CYP3A4 and an inducer of CYP1A2 and possibly CYP2C9. Caution and close monitoring are advised if these drugs are administered together.
Rucaparib: (Major) Avoid coadministration of alosetron and rucaparib unless clinically necessary due to the risk of increased plasma concentrations of alosetron. Alosetron is a CYP1A2 substrate and rucaparib is a moderate CYP1A2 inhibitor. Coadministration with a strong CYP1A2 inhibitor increased alosetron exposure by approximately 6-fold and prolonged the half-life by approximately 3-fold. Concomitant use with moderate CYP1A2 inhibitors has not been evaluated, but is expected to have similar potential drug interactions.
Saquinavir: (Moderate) Concomitant use of alosetron with saquinavir may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; boosted saquinavir is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Scopolamine: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Sedating H1-blockers: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
St. John's Wort, Hypericum perforatum: (Moderate) Alosetron is metabolized by hepatic cytochrome P450 enzymes CYP2C9, CYP3A4, and CYP1A2. Inducers of these enzymes, such as St. John's Wort, can reduce the systemic exposure to alosetron by increasing the metabolism of the drug.
Stiripentol: (Moderate) Consider a dose adjustment of alosetron when coadministered with stiripentol. Coadministration may alter plasma concentrations of alosetron resulting in an increased risk of adverse reactions and/or decreased efficacy. Alosetron is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Streptogramins: (Moderate) Dalfopristin; quinupristin is a major inhibitor of cytochrome P450 3A4 and may decrease the elimination of drugs metabolized by this enzyme including alosetron.
Sufentanil: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Tapentadol: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Teriflunomide: (Moderate) Use caution when administering teriflunomide and alosetron concurrently. In vivo data suggest that teriflunomide is a weak inducer of CYP1A2. Coadministration of teriflunomide with CYP1A2 substrates, such as alosetron, may decrease alosetron exposure and lead to a reduction in efficacy.
Thioridazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Tramadol: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Tramadol; Acetaminophen: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Tricyclic antidepressants: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Trifluoperazine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like phenothiazines, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Trihexyphenidyl: (Major) Concomitant use of alosetron and anticholinergics, which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid anticholinergics in patients taking alosetron.
Trimipramine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like tricyclic antidepressants, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Triprolidine: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Trospium: (Major) Concomitant use of alosetron and trospium, an antimuscarinic which can decrease GI motility, may seriously worsen constipation, leading to events such as GI obstuction, impaction, or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid antimuscarinics in patients taking alosetron.
Tucatinib: (Moderate) Concomitant use of alosetron with tucatinib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; tucatinib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and alosetron may result in altered concentrations of alosetron. Vemurafenib is an inhibitor of CYP1A2 and CYP2C9 and an inducer of CYP3A4. Alosetron is a substrate of CYP1A2, CYP2C9, and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
Viloxazine: (Contraindicated) Concomitant use of viloxazine and alosetron is contraindicated due to the increased risk for alosetron-related adverse effects and exposure. Alosetron is a CYP1A2 substrate and viloxazine is a strong CYP1A2 inhibitor. Coadministration of another strong CYP1A2 inhibitor increased the mean alosetron AUC by about 6-fold and prolonged the half-life by 3-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Concomitant use of alosetron with clarithromycin may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; clarithromycin is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Voriconazole: (Moderate) Concomitant use of alosetron with voriconazole may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; voriconazole is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Zafirlukast: (Minor) Alosetron is metabolized by hepatic cytochrome P450 enzymes CYP2C9, CYP3A4 and CYP1A2. Inhibitors of these enzymes, such as zafirlukast, may decrease the clearance of alosetron and increase the systemic exposure of alosetron. Clinically, increased systemic exposure to alosetron may cause or worsen constipation, which might lead to serious adverse effects.

Alosetron/Alosetron Hydrochloride/Lotronex Oral Tab: 0.5mg, 1mg

Adults

2 mg/day PO.

Geriatric

2 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Alosetron is a potent and selective antagonist at serotonin 5-HT3 receptors which are nonselective cation channels. 5-HT3 receptors are extensively distributed on enteric neurons in the human gastrointestinal (GI) tract, as well as other peripheral and central locations. Antagonism at these receptors in the GI tract modulate the regulation of visceral pain, colonic transit, and GI secretions. Patients with irritable bowel syndrome have visceral hypersensitivity and hyperactivity of the GI tract, which lead to abnormal sensations of pain and motor activity. Following distention of the rectum, patients with IBS exhibit pain and discomfort at lower volumes than patients with normal bowel activity. Administration of alosetron to patients with IBS reduces pain and attenuates exaggerated motor responses, possibly through antagonism at 5-HT3 receptors. In clinical trials often utilizing higher doses than those currently approved, alosetron increased colonic transit time without affecting orocecal transit time. Basal jejunal water and sodium absorption were also increased. Single oral doses of alosetron have produced a dose-dependent reduction in the flare response seen after an intradermal injection of serotonin.

Alosetron is administered orally. It is extensively metabolized in the liver, however, the biological activity of the metabolites is unknown. In vitro data suggest that cytochrome P450 enzyme metabolism accounts for roughly 58% (30%-CYP2C9; 18%-CYP3A4; and 10%-CYP1A2) of an administered dose. Non-CYP metabolism accounts for roughly 11% of the dose. However, in vivo data suggest that CYP1A2 metabolism accounts for 62—97% of the clearance. Based on radiolabeled studies, at least 13 metabolites have been detected in urine with the predominant one being a 6-hydroxy metabolite (15% of the dose) which was secondarily metabolized to a glucuronide metabolite (14% of the dose). Smaller amounts of both metabolites also were present in the feces. One other metabolite, a bis-oxidized dicarbonyl, accounted for 14% of an administered dose. No other urinary metabolite accounted for more than 4% of the dosage. Additionally, an N-desmethyl metabolite was found in the plasma of all Japanese men studied and accounted for up to 30% of the dose in one subject when alosetron was administered with food. The clinical significance of the metabolites is not known; although only the bis-oxidized dicarbonyl metabolite is likely to exert any pharmacological activity (approximately 10-fold less potent than alosetron). Plasma radioactivity declined with a half-life 2-fold longer than alosetron, indicating that circulating metabolites were present. Approximately 74% of an administered dose is excreted in urine and 11% in feces. Only 1% of the drug has been recovered in the feces as unchanged drug. Renal elimination of unchanged drug accounts for only 13% of the dose. The terminal elimination half-life of alosetron is roughly 1.5 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9, CYP3A4, CYP1A2, N-acetyltransferase
In vitro and in vivo data suggest that it is unlikely that alosetron will inhibit the hepatic metabolic clearance of other drugs metabolized by these enzymes. Further, these data also suggest that other hepatic enzymes (e.g., CYP2D6, CYP2C19, or CYP2E1) are not inhibited by alosetron. It may inhibit the metabolism of drugs metabolized by N-acetyltransferase (e.g., isoniazid, INH; hydralazine; procainamide), however, this interaction has not been studied. Alosetron does not appear to induce the CYP3A family of enzymes, CYP2E1 or CYP2C19. It is not known if alosetron could induce other isozymes.

Oral Route

Following administration, it is rapidly absorbed with a mean absolute bioavailability of about 50—60%. Peak plasma concentrations occur in 1 hour; higher peak plasma concentrations occur in young women (9 ng/mL) as compared to young men (5 ng/mL). Administration with food decreases absorption by about 25% with a mean delay in time to peak concentration of 15 minutes. Alosetron is distributed throughout the body and plasma protein binding is 82% over a concentration range of 20 to 4000 ng/mL.
 
An N-desmethyl metabolite was found in the plasma of all Japanese men studied and accounted for up to 30% of the dose in one subject when alosetron was administered with food.

Pregnancy

The available data with alosetron use in human pregnancy are insufficient to draw conclusions about any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of alosetron during the period of organogenesis to pregnant rats at doses up to 40 mg/kg/day (about 160 times the recommended human dose based on body surface area) or to pregnant rabbits at doses up to 30 mg/kg/day (about 240 times the recommended daily human dose based on body surface area).[28382]

There are no data regarding the presence of alosetron in human milk, the effects on the breastfed infant, or the effects on milk production. Alosetron should be used cautiously in lactating women; in general, use is recommended to be avoided during breast-feeding, given the risk of serious complications that may be possible in the infant from drug exposure (e.g., ischemic colitis). Alosetron and/or metabolites of alosetron are present in the breast milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Monitor infants exposed to alosetron through breast milk for severe constipation and blood in stools.[28382] 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. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.