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  • CLASSES

    Serotonin Receptor Antagonists for IBS-D

    DEA CLASS

    Rx

    DESCRIPTION

    Selective serotonin 5-HT3 receptor antagonist
    Approved only for females with severe diarrhea-predominant IBS failing to respond to conventional therapy
    Black Box warning on product label regarding severe constipation and ischemic colitis

    COMMON BRAND NAMES

    Lotronex

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    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 one 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: The safety and effectiveness of alosetron in men have not been established.
    Oral dosage
    Adult females

    Initially, 0.5 mg PO twice daily for 4 weeks. If constipation develops during the initial 4 weeks, stop treatment until constipation resolves. Treatment may be re-initiated at 0.5 mg PO once daily. If constipation develops with the once daily dosing, the drug must be permanently discontinued. Conversely, if the drug is well tolerated during the initial 4 weeks but IBS symptoms are not adequately controlled, the dose may be increased to 1 mg PO twice per day for 4 weeks. Discontinue the drug in those patients whose symptoms are not adequately controlled after 4 weeks of treatment with 1 mg PO twice per day. Although the efficacy of 0.5 mg PO twice daily has not been adequately studied, the lower starting dose has been found to decrease the risk of constipation. Discontinue the drug immediately in patients who develop constipation or signs of ischemic colitis. Do not restart in patients who develop ischemic colitis. Elderly women, debilitated patients, or patients taking medications that decrease GI motility may be more prone to complications from constipation and should be closely monitored.

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    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.

    ADMINISTRATION

     
    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.

    STORAGE

    Lotronex:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    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.

    Anticholinergic medications, geriatric

    Alosetron should be used cautiously in geriatric or debilitated patients, or those receiving medications that slow down the motility of the GI tract (e.g., anticholinergic medications). These patients are at a greater risk for serious complications from constipation and should be monitored carefully.

    Hepatic disease

    Until further data become available, alosetron is contraindicated for use in patients with severe hepatic disease (impairment), and should be used cautiously in patients with mild to moderate hepatic disease. Alosetron and its metabolites have extensive hepatic metabolism; increased systemic exposure to alosetron is likely to occur in patients with any hepatic impairment. A small single dose study of alosetron 1 mg in those with moderate or severe hepatic impairment compared to historic healthy control subjects indicated that a female subject with severe hepatic impairment had a 14 fold greater systemic exposure to the drug than healthy control females. Another female subject with moderate hepatic impairment had a 1.6 fold higher exposure than healthy females.

    Renal failure, renal impairment

    Alosetron pharmacokinetics are not appreciably affected by renal impairment. However, the effects of renal impairment or renal failure on the metabolites of alosetron have not been assessed. Until further data are available, caution is advised in using alosetron in patients with renal impairment. It is not known if dosage adjustments are needed.

    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]

    Breast-feeding

    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.

    Children, infants, neonates

    The safety and effectiveness of alosetron in neonates, infants, children and adolescents less than 18 years of age have not been established. Because of the serious complications of ischemic colitis and constipation that has been observed in adults, use in children is not recommended.

    ADVERSE REACTIONS

    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

    DRUG INTERACTIONS

    Acetaminophen; Butalbital; 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.
    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; Magnesium Salicylate; Phenyltoloxamine: (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; Phenyltoloxamine; Salicylamide: (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; Phenyltoloxamine: (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; 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; 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; Propoxyphene: (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.
    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.
    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.
    Amitriptyline; Chlordiazepoxide: (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; Lansoprazole: (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%.
    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%.
    Amprenavir: (Moderate) Amprenavir inhibits cytochrome P450 3A4. Although specific interactions have not been studied, amprenavir may interfere with the metabolism of CYP3A4 substrates, such as alosetron, and caution is warranted with coadministration.
    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: (Severe) 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.
    Aspirin, ASA; Butalbital; 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.
    Aspirin, ASA; 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.
    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; 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.
    Atropine; Difenoxin: (Severe) 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.
    Atropine; Diphenoxylate: (Severe) 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.
    Atropine; Edrophonium: (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; Hyoscyamine; Phenobarbital; 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.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (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.
    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.
    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.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering alosetron with boceprevir due to an increased potential for alosetron-related adverse events. If alosetron dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of alosetron. Alosetron is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated alosetron plasma concentrations.
    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; Carbetapentane; 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; Dextromethorphan; Guaifenesin: (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; 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. (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; 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. (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.
    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.
    Cannabidiol: (Moderate) Consider a dose adjustment of alosetron when coadministered with cannabidiol. 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 cannabidiol potentially resulting in clinically significant 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; 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.
    Carbetapentane; 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.
    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.
    Carbinoxamine; 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.
    Carbinoxamine; Hydrocodone; 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.
    Carbinoxamine; 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. (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.
    Carbinoxamine; 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.
    Carbinoxamine; 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.
    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; 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; 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; Dihydrocodeine; 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. (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; Guaifenesin; 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. (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; Hydrocodone; 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; 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. (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; 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: (Severe) 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%.
    Dasabuvir; Ombitasvir; Paritaprevir; 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.
    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.
    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; 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.
    Dextromethorphan; 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.
    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.
    Dihydrocodeine; 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.
    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; Hydrocodone; 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.
    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.
    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.
    Erythromycin; Sulfisoxazole: (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.
    Fluoxetine; 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.
    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: (Severe) 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.
    Guaifenesin; 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.
    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; Hydrochlorothiazide, HCTZ: (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; 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.
    Hydrocodone; Potassium Guaiacolsulfonate: (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; Potassium Guaiacolsulfonate; 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.
    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) Alosetron is partially metabolized by CYP3A4. Ketoconazole is an inhibitor of CYP3A4. Caution should be used if these drugs are coadministered. In a study of healthy female subjects, ketoconazole 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%.
    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.
    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.
    Mepenzolate: (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.
    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.
    Meperidine; 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.
    Mephobarbital: (Minor) Alosetron is metabolized by CYP1A2 and CYP3A4. Phenobarbital (the major metabolite of mephobarbital) can induce the activity of these enzymes and increase the metabolism of alosetron. Concomitant administration of phenobarbital and alosetron has not been evaluated.
    Mesoridazine: (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.
    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.
    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.
    Norfloxacin: (Moderate) Alosetron is metabolized by CYP1A2. Norfloxacin inhibits CYP1A2 isoenzymes and may decrease the metabolism of alosetron resulting in increased alosetron plasma concentrations.
    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.
    Obeticholic Acid: (Major) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as alosetron. Therapeutic monitoring is recommended with coadministration. Elevated alosetron concentrations may cause severe constipation.
    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.
    Ombitasvir; Paritaprevir; 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.
    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.
    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.
    Phenylephrine; 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.
    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.
    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.
    Propoxyphene: (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.
    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.
    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%.
    Rifamycins: (Minor) Alosetron is metabolized by hepatic cytochrome P450 enzymes CYP2C9 (30%), CYP3A4 (18%) and CYP1A2 (10%). Inducers of CYP1A2, CYP2C9, and CYP3A4, such as rifamycins, can reduce the systemic exposure to alosetron by increasing the metabolism of the drug. Rifampin induces both CYP3A4 and CYP1A2, rifapentine induces CYP3A4 and CYP2C89, and rifabutin induces CYP3A4. Appropriate clinical monitoring is recommended if these drugs must be used concomitantly.
    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.
    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.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering alosetron with telaprevir due to an increased potential for alosetron-related adverse events. If alosetron dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of alosetron. Alosetron is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated alosetron plasma concentrations.
    Telithromycin: (Moderate) Concomitant use of alosetron with telithromycin 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; telithromycin is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
    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.
    Thiabendazole: (Moderate) Thiabendazole may inhibit CYP1A2. Since alosetron is metabolized by CYP1A2, thiabendazole may decrease the metabolism of alosetron resulting in increased alosetron plasma concentrations. Coadministration of alosetron with thiabendazole has not been studied.
    Thiethylperazine: (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.
    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.
    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.
    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.
    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.
    Zileuton: (Major) Concomitant use of alosetron with zileuton should be avoided due to the risk for increased alosetron serum concentrations and serious adverse reactions. Alosetron is metabolized by CYP1A2; zileuton is a moderate inhibitor of this enzyme.

    PREGNANCY AND LACTATION

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.