Alosetron Hydrochloride
Tablet, Film Coated · Oral
Uses
Alosetron tablets are indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and not responded adequately to conventional therapy. Diarrhea-predominant IBS is severe if it includes diarrhea and one or more of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or fecal incontinence, disability or restriction of daily activities due to IBS. Because of infrequent but serious gastrointestinal adverse reactions associated with alosetron tablets, the indication is restricted to those patients for whom the benefit-to-risk balance is most favorable. Clinical studies have not been performed to adequately confirm the benefits of alosetron tablets in men. Alosetron Tablets are a selective serotonin 5-HT3 antagonist indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and not responded adequately to conventional therapy. ( 1 ) Severe IBS includes diarrhea and 1 or more of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or fecal incontinence, disability or restriction of daily activities due to IBS. ( 1 )
Dosage and administration
Starting dose is 0.5 mg twice a day ( 2.1 ) May increase dose to 1 mg twice a day after 4 weeks if starting dosage is well tolerated but does not adequately control IBS symptoms ( 2.1 ) Discontinue alosetron tablets in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg twice a day. ( 2.1 ) 2.1 Adult Patients To lower the risk of constipation, alosetron tablets should be started at a dosage of 0.5 mg twice a day. Patients who become constipated at this dosage should stop taking alosetron tablets until the constipation resolves. They may be restarted at 0.5 mg once a day. If constipation recurs at the lower dose, alosetron tablets should be discontinued immediately. Patients well controlled on 0.5 mg once or twice a day may be maintained on this regimen. If after 4 weeks the dosage is well tolerated but does not adequately control IBS symptoms, then the dosage can be increased to up to 1 mg twice a day. Alosetron tablets should be discontinued in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg twice a day. Alosetron tablets can be taken with or without food [see Clinical Pharmacology ( 12.3 )]. Alosetron tablets should be discontinued immediately in patients who develop constipation or signs of ischemic colitis. Alosetron tablets should not be restarted in patients who develop ischemic colitis. Clinical trial and postmarketing experience suggest that debilitated patients or patients taking additional medications that decrease gastrointestinal motility may be at greater risk of serious complications of constipation. Therefore, appropriate caution and follow-up should be exercised if alosetron tablets are prescribed for these patients. Postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation; therefore, appropriate caution and follow-up should be exercised if alosetron tablets are prescribed for these patients [see Warnings and Precautions ( 5.1 )]. 2.2 Patients with Hepatic Impairment Alosetron tablets are extensively metabolized by the liver, and increased exposure to alosetron tablets are likely to occur in patients with hepatic impairment. Increased drug exposure may increase the risk of serious adverse reactions. Alosetron tablets should be used with caution in patients with mild or moderate hepatic impairment and is contraindicated in patients with severe hepatic impairment [see Contraindications (4), Use in Specific Populations ( 8.6 )].
Dosage forms and strengths
0.5 mg and 1 mg tablets Alosetron Tablets, USP 0.5 mg (0.562 mg alosetron hydrochloride, USP equivalent to 0.5 mg alosetron), are white, oval shaped tablet debossed with “E” on one side and “3” on the other side. Alosetron Tablets, USP 1 mg (1.124 mg alosetron hydrochloride, USP equivalent to 1 mg alosetron), are white, oval shaped tablet debossed with “E” on one side and “4” on the other side. Tablets: 0.5 and 1 mg
Contraindications
Do not initiate in patients with constipation ( 4.1 ) History of chronic or severe constipation or sequelae from constipation; intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions; ischemic colitis; impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; Crohn’s disease or ulcerative colitis; diverticulitis; severe hepatic impairment ( 4.2 ) Concomitant use of fluvoxamine ( 4.3 ) 4.1 Constipation Alosetron tablets should not be initiated in patients with constipation [see Warnings and Precautions ( 5.1 )]. 4.2 History of Severe Bowel or Hepatic Disorders Alosetron tables are contraindicated in patients with a history of the following: chronic or severe constipation or sequelae from constipation intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesions ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state Crohn’s disease or ulcerative colitis diverticulitis severe hepatic impairment 4.3 Concomitant Use of Fluvoxamine Concomitant administration of alosetron tablets with fluvoxamine is contraindicated. Fluvoxamine, a known strong inhibitor of CYP1A2, has been shown to increase mean alosetron plasma concentrations (AUC) approximately 6-fold and prolong the half-life by approximately 3-fold [see Drug Interactions ( 7.1 )].
Warnings and precautions
Serious Complications of Constipation: May occur in some patients without warning. Includes obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia and in rare cases perforation and death have been reported. Risk is increased in patients who are elderly, debilitated, or taking medications that decrease bowel motility. ( 5.1 ) Discontinue alosetron tablets immediately if constipation occurs. ( 5.1 ) Ischemic colitis: May occur in some patients without warning. Promptly evaluate patients with signs of ischemic colitis (e.g., rectal bleeding, bloody diarrhea, new or worsening abdominal pain). ( 5.2 ) Discontinue alosetron tablets immediately if signs of ischemic colitis occur, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain. ( 5.2 ) 5.1 Serious Complications of Constipation Some patients have experienced serious complications of constipation without warning. Serious complications of constipation, including obstruction, ileus, impaction, toxic megacolon, and secondary bowel ischemia, have been reported with use of alosetron tablets during clinical trials. Complications of constipation have been reported with use of 1 mg twice daily and with lower doses. A dose response relationship has not been established for serious complications of constipation. The incidence of serious complications of constipation was approximately 0.1% (1 per 1,000 patients) in women receiving either alosetron tablets or placebo. In addition, rare cases of perforation and death have been 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. Alosetron tablets should be discontinued immediately in patients who develop constipation [see Boxed Warning ]. 5.2 Ischemic Colitis Some patients have experienced ischemic colitis without warning. Ischemic colitis has been reported in patients receiving alosetron tablets in clinical trials as well as during marketed use of the drug. In IBS clinical trials, the cumulative incidence of ischemic colitis in women receiving alosetron tablets was 0.2% (2 per 1,000 patients, 95% confidence interval 1 to 3) through 3 months and was 0.3% (3 per 1,000 patients, 95% confidence interval 1 to 4) through 6 months. Ischemic colitis has been 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 the incidence of ischemic colitis in patients taking alosetron tablets for longer than 6 months. Alosetron tablets should be discontinued immediately in patients with signs of ischemic colitis such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain. Because ischemic colitis can be life-threatening, patients with signs or symptoms of ischemic colitis should be evaluated promptly and have appropriate diagnostic testing performed. Treatment with alosetron tablets should not be resumed in patients who develop ischemic colitis.
Side effects
The following adverse reactions are described in more detail in other sections of the label: Complications of constipation [see Boxed Warning , Warnings and Precautions ( 5.1 )] Ischemic colitis [see Boxed Warning , Warnings and Precautions ( 5.2 )] Most common adverse reactions (incidence >2% and >placebo) in clinical studies were constipation, abdominal discomfort and pain, nausea, and gastrointestinal discomfort and pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hibrow Healthcare Private Limited at 1-888-400-7422 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients with Irritable Bowel Syndrome: Table 1 summarizes adverse reactions from 22 repeat-dose studies in patients with IBS who were treated with 1 mg of alosetron tablets twice daily for 8 to 24 weeks. The adverse reactions in Table 1 were reported in 1% or more of patients who received alosetron tablets and occurred more frequently on alosetron tablets than on placebo. A statistically significant difference was observed for constipation in patients treated with alosetron tablets compared to placebo (p<0.0001). Table 1 . Adverse Reactions Reported in ≥1% of Patients with Irritable Bowel Syndrome and More Frequently on Alosetron tablets 1 mg Twice Daily Than Placebo Body System Adverse Reaction Placebo (n = 2,363) Alosetron Tablets 1 mg twice daily (n = 8,328) Gastrointestinal Constipation Abdominal discomfort and pain Nausea Gastrointestinal discomfort and pain Abdominal distention Regurgitation and reflux Hemorrhoids 6% 4% 5% 3% 1% 2% 1% 29% 7% 6% 5% 2% 2% 2% Gastrointestinal: Constipation is a frequent and dose-related side effect of treatment with alosetron tablets [see Warnings and Precautions ( 5.1 )]. In clinical studies constipation was reported in approximately 29% of patients with IBS treated with alosetron tablets 1 mg twice daily (n = 9,316). This effect was statistically significant compared to placebo (p<0.0001). Eleven percent (11%) of patients treated with alosetron tablets1 mg twice daily withdrew from the studies due to constipation. Although the number of patients with IBS treated with alosetron tablets 0.5 mg twice daily is relatively small (n = 243), only 11% of those patients reported constipation and 4% withdrew from clinical studies due to constipation. Among the patients treated with alosetron tablets 1 mg twice daily who reported constipation, 75% reported a single episode and most reports of constipation (70%) occurred during the first month of treatment, with the median time to first report of constipation onset of 8 days. Occurrences of constipation in clinical trials were generally mild to moderate in intensity, transient in nature, and resolved either spontaneously with continued treatment or with an interruption of treatment. However, serious complications of constipation have been reported in clinical studies and in postmarketing experience [see Boxed Warning and Warnings and Precautions ( 5.1 )]. In Studies 1 and 2, 9% of patients treated with alosetron tablets reported constipation and 4 consecutive days with no bowel movement [see Clinical Studies ( 14.2 )]. Following interruption of treatment, 78% of the affected patients resumed bowel movements within a 2-day period and were able to re-initiate treatment with alosetron tablets. Hepatic: A similar incidence in elevation of ALT (>2-fold) was seen in patients receiving alosetron tablets or placebo (1.0% vs. 1.2%). A single case of hepatitis (elevated ALT, AST, alkaline phosphatase, and bilirubin) without jaundice in a patient receiving alosetron tablets was reported in a 12-week study. A causal association with alosetron tablets has not been established. Long-Term Safety: Patient experience in controlled clinical trials is insufficient to estimate the incidence of ischemic colitis in patients taking alosetron tablets for longer than 6 months. Women with Severe Diarrhea-Predominant Irritable Bowel Syndrome: Table 2 summarizes the gastrointestinal adverse reactions from 1 repeat-dose study in female patients with severe diarrhea-predominant IBS who were treated for 12 weeks. The adverse reactions in Table 2 were reported in 3% or more of patients who received alosetron tablets and occurred more frequently with alosetron tablets than with placebo. Other events reported in 3% or more of patients who received alosetron tablets and occurring more frequently with alosetron tablets than with placebo included upper respiratory tract infection, viral gastroenteritis, muscle spasms, headaches, and fatigue. Table 2. Gastrointestinal Adverse Reactions Reported in ≥ 3% of Women with Severe Diarrhea-Predominant Irritable Bowel Syndrome and More Frequently on Alosetron Tablets Than Placebo. Adverse Reaction Placebo (n = 176) Alosetron tablets 0.5 mg once daily (n = 175) Alosetron tablets 1 mg once daily (n = 172) Alosetron tablets 1 mg twice daily (n = 176) Constipation Abdominal pain Diarrhea Hemorrhoidal hemorrhage Flatulence Hemorrhoids Abdominal pain upper 5% 3% 2% 2% 2% 2% 1% 9% 5% 3% 3% 2% 1% 3% 16% 6% 2% 2% 1% 1% 1% 19% 7% 2% 2% 3% 3% 1% Adverse reactions reported in another study of 701 women with severe diarrhea-predominant IBS were similar to those shown in Table 2 . Gastrointestinal adverse reactions reported in 3% or more of patients who received alosetron tablets and occurring more frequently with alosetron tablets than with placebo included constipation (14% and 10% of patients taking alosetron tablets 1 mg twice daily or 0.5 mg as needed, respectively, compared with 2% taking placebo), abdominal pain, nausea, vomiting, and flatulence.
Drug interactions
In vivo data suggest that alosetron is primarily metabolized by cytochrome P450 (CYP) 1A2, with minor contributions from CYP3A4 and CYP2C9. Therefore, inducers or inhibitors of these enzymes may change the clearance of alosetron. CYP1A2 inhibitors: Avoid concomitant uses because of increased exposure and half-life of alosetron. Use with fluvoxamine is contraindicated. ( 4.3 , 7.1 ) CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. ( 7.2 ) 7.1 CYP1A2 Inhibitors Fluvoxamine is a known strong inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. In a pharmacokinetic study, 40 healthy female subjects received fluvoxamine in escalating doses from 50 to 200 mg/ day for 16 days, with coadministration of alosetron 1 mg on the last day. Fluvoxamine increased mean alosetron plasma concentrations (AUC) approximately 6-fold and prolonged the half-life by approximately 3-fold. Concomitant administration of alosetron and fluvoxamine is contraindicated [see Contraindications ( 4.3 )]. Concomitant administration of alosetron and moderate CYP1A2 inhibitors, including quinolone antibiotics and cimetidine, has not been evaluated, but should be avoided unless clinically necessary because of similar potential drug interactions. 7.2 CYP3A4 Inhibitors Ketoconazole is a known strong inhibitor of CYP3A4. In a pharmacokinetic study, 38 healthy female subjects received ketoconazole 200 mg twice daily for 7 days, with coadministration of alosetron 1 mg on the last day. Ketoconazole increased mean alosetron plasma concentrations (AUC) by 29%. Caution should be used when alosetron and ketoconazole are administered concomitantly. Coadministration of alosetron and strong CYP3A4 inhibitors such as clarithromycin, telithromycin, protease inhibitors, voriconazole, and itraconazole has not been evaluated but should be undertaken with caution because of similar potential drug interactions. The effect of induction or inhibition of other pathways on exposure to alosetron and its metabolites is not known. 7.3 Other CYP Enzymes In vitro human liver microsome studies and an in vivo metabolic probe study demonstrated that alosetron did not inhibit CYP enzymes 3A4, 2C9, or 2C19. In vitro at total drug concentrations 27-fold higher than peak plasma concentrations observed with the 1 mg dose, alosetron inhibited CYP enzymes 1A2 (60%) and 2E1 (50%). In an in vivo metabolic probe study, alosetron did not inhibit CYP2E1 but did produce 30% inhibition of both CYP1A2 and N-acetyltransferase. Although not studied with alosetron, inhibition of N-acetyltransferase may have clinically relevant consequences for drugs such as isoniazid, procainamide, and hydralazine. The effect on CYP1A2 was explored further in a clinical interaction study with theophylline and no effect on metabolism was observed. Another study showed that alosetron had no clinically significant effect on plasma concentrations of the oral contraceptive agents ethinyl estradiol and levonorgestrel (CYP3A4 substrates). A clinical interaction study was also conducted with alosetron and the CYP3A4 substrate cisapride. No significant effects on cisapride metabolism or QT interval were noted. The effects of alosetron on monoamine oxidases and on intestinal first pass secondary to high intraluminal concentrations have not been examined. Based on the above data from in vitro and in vivo studies, it is unlikely that alosetron will inhibit the hepatic metabolic clearance of drugs metabolized by the CYP enzymes 2C9, 2C19, or 2E1. Alosetron does not appear to induce the major cytochrome P450 drug-metabolizing enzyme 3A. Alosetron also does not appear to induce CYP enzymes 2E1 or 2C19. It is not known whether alosetron might induce other enzymes.
Use in specific populations
Hepatic impairment: Contraindicated in severe hepatic impairment. Use with caution in patients with mild or moderate hepatic impairment. ( 4.2 , 8.6 ) Geriatric use: Elderly patients may be at greater risk for complications of constipation. ( 8.5 ) 8.1 Pregnancy Risk Summary The available data with alosetron tablets 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. 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 (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and miscarriage is 15 to 20%, respectively. Data Animal Data 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). 8.2 Lactation Risk Summary 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 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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for alosetron tablets and any potential adverse effects on the breastfed infant from alosetron tablet or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to alosetron tablets through breast milk for severe constipation and blood in stools. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Use of alosetron tablets is not recommended in the pediatric population, based upon the risk of serious complications of constipation and ischemic colitis in adults. 8.5 Geriatric Use In some studies in healthy men or women, plasma concentrations were elevated by approximately 40% in individuals 65 years and older compared to young adults [see Warnings and Precautions ( 5.1 )] . However, this effect was not consistently observed in men. Postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation therefore, appropriate caution and follow-up should be exercised if alosetron tablets are prescribed for these patients [see Warnings and Precautions ( 5.1 )] . 8.6 Hepatic Impairment Due to the extensive hepatic metabolism of alosetron, increased exposure to alosetron and/or its metabolites is likely to occur in patients with hepatic impairment. Alosetron should not be used in patients with severe hepatic impairment and should be used with caution in patients with mild or moderate hepatic impairment. A single 1 mg oral dose of alosetron was administered to 1 female and 5 male patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) and to 1 female and 2 male patients with severe hepatic impairment (Child-Pugh score of >9). In comparison with historical data from healthy subjects, patients with severe hepatic impairment displayed higher systemic exposure to alosetron. The female with severe hepatic impairment displayed approximately 14-fold higher exposure, while the female with moderate hepatic impairment displayed approximately 1.6-fold higher exposure, than healthy females. Due to the small number of subjects and high intersubject variability in the pharmacokinetic findings, no definitive quantitative conclusions can be made. However, due to the greater exposure to alosetron in the female with severe hepatic impairment, alosetron should not be used in females with severe hepatic impairment [see Dosage and Administration ( 2.2 ), Contraindications ( 4 )] . 8.7 Renal Impairment Renal impairment (creatinine clearance 4 to 56 mL/min) has no effect on the renal elimination of alosetron due to the minor contribution of this pathway to elimination. The effect of renal impairment on metabolite pharmacokinetics and the effect of end-stage renal disease have not been assessed.
Pregnancy
8.1 Pregnancy Risk Summary The available data with alosetron tablets 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. 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 (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and miscarriage is 15 to 20%, respectively. Data Animal Data 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).
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Use of alosetron tablets is not recommended in the pediatric population, based upon the risk of serious complications of constipation and ischemic colitis in adults.
Geriatric use
8.5 Geriatric Use In some studies in healthy men or women, plasma concentrations were elevated by approximately 40% in individuals 65 years and older compared to young adults [see Warnings and Precautions ( 5.1 )] . However, this effect was not consistently observed in men. Postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation therefore, appropriate caution and follow-up should be exercised if alosetron tablets are prescribed for these patients [see Warnings and Precautions ( 5.1 )] .
Overdosage
There is no specific antidote for overdose of alosetron tablets. Patients should be managed with appropriate supportive therapy. Individual oral doses as large as 16 mg have been administered in clinical studies without significant adverse reactions. This dose is 8 times higher than the recommended total daily dose. Inhibition of the metabolic elimination and reduced first pass of other drugs might occur with overdoses of alosetron tablets [see Drug Interactions ( 7 )].
Description
The active ingredient in alosetron tablets, USP is alosetron hydrochloride (HCl), USP a potent and selective antagonist of the serotonin 5-HT3 receptor type. Chemically, alosetron is designated as 2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl-1H-imidazol-4 yl)methyl]-1H-pyrido[4,3-b]indol-1-one, monohydrochloride. Alosetron is achiral and has the empirical formula C 17 H 18 N 4 O
• HCl, representing a molecular weight of 330.8. Alosetron is a white to pale brown colored powder that has a solubility of 66.82 mg/mL in water, 83.34 mg/mL in 0.1N hydrochloric acid, 74.65 mg/mL in pH 6.8 phosphate buffer, and 60.79 mg/mL in pH 8.0 phosphate buffer. The chemical structure of alosetron is: Alosetron Tablets USP are supplied for oral administration as 0.5 mg (white) and 1 mg (white) tablets. The 0.5 mg tablet contains 0.562 mg alosetron hydrochloride, USP equivalent to 0.5 mg alosetron, and the 1 mg tablet contains 1.124 mg alosetron hydrochloride, USP equivalent to 1 mg of alosetron. Each tablet also contains the inactive ingredients lactose (anhydrous), magnesium stearate, microcrystalline cellulose, and pregelatinized starch. The white film coat for the 0.5 mg tablet contains hypromellose, titanium dioxide, macrogol and triacetin. The white film coat for the 1 mg tablet contains hypromellose, titanium dioxide, macrogol and triacetin. alo-str.jpg
Mechanism of action
12.1 Mechanism of Action Alosetron is a potent and selective 5-HT3 receptor antagonist. 5-HT3 receptors are ligand-gated cation channels that are extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels and the resulting neuronal depolarization affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions, processes that relate to the pathophysiology of IBS. 5-HT3 receptor antagonists such as alosetron inhibit activation of non-selective cation channels, which results in the modulation of the enteric nervous system. The cause of IBS is unknown. IBS is characterized by visceral hypersensitivity and hyperactivity of the gastrointestinal 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 healthy volunteers. Following such distention, alosetron reduced pain and exaggerated motor responses, possibly due to blockade of 5-HT3 receptors.
How supplied
Alosetron Tablets, USP 0.5 mg (0.562 mg alosetron hydrochloride, USP equivalent to 0.5 mg alosetron) are white, oval shaped tablet, debossed “E” on one side and “3” on the other side. Bottles of 30 (NDC 71930-010-30) with child-resistant closures. Alosetron Tablets, USP 1 mg (1.124 mg alosetron hydrochloride, USP equivalent to 1 mg alosetron), are white, oval shaped tablet, debossed “E” on one side and “4” on the other side. Bottles of 30 (NDC 71930-011-30) with child-resistant closures. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.
Patient information
17 PATIENT COUNSELING INFORMATION and Medication Guide Advise the patient to read the FDA-approved patient labelling (Medication Guide). Prescriber and Patient Responsibilities Patients should be fully counseled on and understand the risks and benefits of alosetron tablets before an initial prescription is written. The patient may be educated by the prescriber or a healthcare provider under a prescriber’s direction. Prescribers must : counsel patients for whom alosetron tablets are appropriate about the benefits and risks of alosetron tablets and discuss the impact of IBS symptoms on the patient’s life. review the Medication Guide, which outlines the benefits and risks of alosetron tablets, and instruct the patient to read it carefully. Answer all questions the patient may have about alosetron tablets. The complete text of the Medication Guide is printed at the end of this document. provide each patient with appropriate instructions for taking alosetron tablets. Additional copies of the Medication Guide are available by contacting Hibrow Healthcare Private Limited at 1 888-400-7422. Patients who are prescribed alosetron tablets should be instructed to : read the Medication Guide before starting alosetron tablets and each time they refill their prescription. not start taking alosetron tablets if they are constipated. immediately discontinue alosetron tablets and contact their prescriber if they become constipated, or have symptoms of ischemic colitis such as new or worsening abdominal pain, bloody diarrhea, or blood in the stool. Contact their prescriber again if their constipation does not resolve after discontinuation of alosetron tablets. Resume alosetron tablets only if their constipation has resolved and after discussion with and the agreement of their treating prescriber. stop taking alosetron tablets and contact their prescriber if alosetron tablets does not adequately control IBS symptoms after 4 weeks of taking 1 mg twice a day. MEDICATION GUIDE Alosetron Tablets, USP ( al oh’ se tron' ) Read the Medication Guide you get with each refill for alosetron tablets. There may be new information. This Medication Guide does not take the place of talking with your doctor. What is the most important information I should know about alosetron tablets? Alosetron tablets is a medicine only for some women with severe chronic irritable bowel syndrome (IBS) whose: main problem is diarrhea and IBS symptoms have not been helped enough by other treatments. Some people have developed serious bowel side effects while taking alosetron tablets. Serious bowel (intestine) side effects can happen suddenly, including the following: Serious complications of constipation: These complications may lead to a hospital stay and, in rare cases, blood transfusions, surgery, and death. People who are older, who are weak from illness, or who take other constipating medicines may be more likely to have serious complications of constipation with alosetron tablets. To lower your chances of getting serious complications of constipation, do the following: If you are constipated , do not start taking alosetron tablets. If you get constipated while taking alosetron tablets , stop taking it right away and call your doctor. If your constipation does not get better after stopping alosetron tablets , call your doctor again. If you stopped taking alosetron tablets, do not start taking alosetron tablets again unless your doctor tells you to do so. Inflammation and injury of the intestines caused by reduced blood flow (ischemic colitis: Ischemic colitis is caused by reduced blood flow to parts of the large bowel. The chance of getting ischemic colitis when you take alosetron tablets for more than 6 months is not known. Ischemic colitis may lead to a hospital stay and, in rare cases, blood transfusions, surgery, and death. Stop taking alosetron tablets and call your doctor or get medical help if you have symptoms of ischemic colitis such as new or worsening stomach-area (abdominal) pain, bloody diarrhea or blood in the stool. What is Alosetron Tablets? Alosetron Tablets are prescription medicine used only for some women with severe chronic IBS whose: main problem is diarrhea and IBS symptoms have not been helped enough by other treatments. Alosetron Tablets does not cure IBS, and it may not help every person who takes it. For those who are helped, alosetron tablets reduces lower stomach area (abdominal) pain and discomfort, the sudden need to have a bowel movement (bowel urgency), and diarrhea from IBS. If you stop taking alosetron Tablets, your IBS symptoms may return within 1 or 2 weeks to what they were before you started taking alosetron tablets. It is not known if alosetron tablets is safe and effective in men with IBS. It is not known if alosetron tablets is safe and effective in children. Who should not take Alosetron Tablets? Do not take alosetron tablets if you: have constipation or you are constipated most of the time. have had a serious problem from constipation. If you are constipated now, do not start taking alosetron tablets. have had serious bowel blockages. have had blood flow problems to your bowels, such as ischemic colitis. have had blood clots. have had Crohn’s disease, ulcerative colitis, diverticulitis, or severe liver disease. are taking fluvoxamine (LUVOX). What should I talk about with my doctor before taking Alosetron tablets? Talk with your doctor: about the possible benefits and risks of Alosetron tablets. about how much of a problem IBS is in your life and what treatments you have tried. about any other illnesses you have and medicines you take or plan to take. These include prescription and non-prescription medicines, supplements, and herbal remedies. Certain illnesses and medicines can increase your chance of getting serious side effects while taking Alosetron tablets. Other medicines may interact with how the body handles Alosetron tablets. any allergies that you have.
Label text from the FDA structured product label by Eywa Pharma Inc (revised Oct 3, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Alosetron Hydrochloride in 8 products
Alosetron Hydrochloride NDC products (8)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 65162-248 | Alosetron Hydrochloride .5 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals LLC | ANDA |
| 65162-249 | Alosetron Hydrochloride 1 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals LLC | ANDA |
| 53746-248 | Alosetron Hydrochloride .5 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals of New York LLC | ANDA |
| 53746-249 | Alosetron Hydrochloride 1 mg/1 Tablet, Film Coated | Amneal Pharmaceuticals of New York LLC | ANDA |
| 73190-035 | Alosetron Hydrochloride .5 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 73190-036 | Alosetron Hydrochloride 1 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 71930-010 | Alosetron Hydrochloride .5 mg/1 Tablet | Eywa Pharma Inc | ANDA |
| 71930-011 | Alosetron Hydrochloride 1 mg/1 Tablet | Eywa Pharma Inc | ANDA |
Frequently asked questions
What is Alosetron Hydrochloride used for?
Alosetron tablets are indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of the gastrointestinal tract excluded, and not responded adequately to conventional therapy. Diarrhea-predominant IBS is severe if it includes diarrhea and one or more of the…
What are the side effects of Alosetron Hydrochloride?
The following adverse reactions are described in more detail in other sections of the label: Complications of constipation [see Boxed Warning , Warnings and Precautions ( 5.1 )] Ischemic colitis [see Boxed Warning , Warnings and Precautions ( 5.2 )] Most common adverse reactions (incidence >2% and >placebo) in clinical studies were constipation, abdominal discomfort and pain, nausea, and… See the full label for the complete list.
Who makes Alosetron Hydrochloride?
Alosetron Hydrochloride is listed by 4 labelers in the FDA NDC directory, including Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals of New York LLC, AvKARE, Eywa Pharma Inc.