Alosetron

Irritable Bowel Syndrome

Irritable Bowel Syndrome Indicated only for women with severe diarrhea-predominant IBS who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of GI tract excluded, and not responded adequately to conventional therapy Initial 0.5 mg PO q12hr for 4 weeks; if well tolerated, but inadequate control of IBS symptoms, increase up to 1 mg q12hr; discontinue if no improvement after 4 weeks

Renal Impairment Dose adjustment not studied in the manufacturer's labeling

Hepatic Impairment Moderate impairment (Child-Pugh score < 9): Use caution Severe dysfunction (Child-Purgh score > 10): Contraindicated

Hypersensitivity Rectal bleeding, history of chronic or severe current constipation History of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, GI perforation or adhesion, thrombophlebitis, history of or current Crohn's disease or ulcerative colitis Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness Inability to comply with the Patient-Physician Agreement for Lotronex Severe hepatic impairment Impaired intestinal circulation Concomitant administration with fluvoxamine Thrombocytopenia

Infrequent but serious GI adverse reactions (eg, ischemic colitis, serious complications of constipation) reported; some have resulted in hospitalization and, rarely, blood transfusion, surgery, or death. In order to prescribe, physicians must be enrolled in Prescribing Program for Alosetron. Indicated only for women with severe diarrhea-predominant irritable bowel syndrome that has not responded adequately to conventional therapy. Discontinue immediately in patients who develop constipation or symptoms of ischemic colitis; do not resume in those who develop ischemic colitis. Patients who have constipation should immediately contact their prescriber if constipation does not resolve after therapy is discontinued; patients with resolved constipa­tion should resume only on the advice of their treating prescriber. Discontinue if inadequate control after 4 weeks of q12hr dosing Use with caution in breast-feeding women Use caution in mild-to-moderate hepatic impairment Constipation Serious complications of constipation, including obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia, reported with use Complications of constipation reported with use of 1 mg twice daily and with lower doses Rare cases of perforation and death reported from postmarketing clinical practice; in some cases, complications of constipation required intestinal surgery, including colectomy Patients who are elderly, debilitated, or taking additional medications that decrease gastrointestinal motility may be at greater risk for complications of constipation; discontinue therapy immediately in patients who develop constipation Ischemic colitis Ischemic colitis reported with use of 1 mg twice daily and with lower doses; a dose-response relationship has not been established; ischemic colitis was reported in one patient receiving placebo; the patient experience in controlled clinical trials is insufficient to estimate incidence of ischemic colitis in patients taking this medicat

Not Classi Pregnancy The available data with use in pregnant women are insufficient to draw conclusions about any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes Animal data In animal reproduction studies, no adverse developmental effects were observed with oral administration of alosetron in rats and rabbits during organogenesis at doses 160 to 240 times, respectively, the recommended human dosage Lactation There are no data regarding presence of drug in human milk, effects on breastfed infant, or on milk production; the drug and/or metabolites of the drug are present in 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; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from therapy or from the underlying maternal condition Monitor infants exposed to drug through breast milk for severe constipation and blood in stools

Contraindicated (3) apomorphine fluvoxamine viloxazine Serious - Use Alternative (24) amobarbital armodafinil butabarbital butalbital carbamazepine cigarette smoking cimetidine ciprofloxacin eluxadoline enasidenib givosiran leniolisib mexiletine pefloxacin peginterferon alfa 2a pentobarbital phenobarbital pipemidic acid primidone secobarbital smoking tobacco use verapamil zileuton

>10% Constipation (29%) 1-10% Abdominal pain (7%) Nausea (6%) Headache (≥3%) GI discomfort and pain (5%) Fatigue (≥3%) Gastroenteritis (>3%) Abdominal distention (2%) Flatulence (1-3%) Regurgitation and reflux (2%) Abdominal distension (2%) Hemorrhoids (2%) Urinary tract infection (≥3%) Muscle spasm (≥3%) Cough (≥3%) Nasopharyngitis (≥3%) <1% Ischemic colitis Anxiety Bone pain Colitis Diverticulitis Cholecystitis GI impaction GI spasms GI ulceration

5-HT3 receptor antagonist; modulates enteric nervous system