Lotronex
alosetron hydrochloride · Tablet · Oral
Uses
1 INDICATIONS AND USAGE LOTRONEX is 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 LOTRONEX, 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 LOTRONEX in men. LOTRONEX is a selective serotonin 5-HT 3 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 LOTRONEX 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, LOTRONEX should be started at a dosage of 0.5 mg twice a day. Patients who become constipated at this dosage should stop taking LOTRONEX until the constipation resolves. They may be restarted at 0.5 mg once a day. If constipation recurs at the lower dose, LOTRONEX 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 . LOTRONEX 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. LOTRONEX can be taken with or without food [see Clinical Pharmacology ( 12.3 )] . LOTRONEX should be discontinued immediately in patients who develop constipation or signs of ischemic colitis. LOTRONEX 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 LOTRONEX is 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 LOTRONEX is prescribed for these patients [see Warnings and Precautions ( 5.1 )] . 2.2 Patients with Hepatic Impairment LOTRONEX is extensively metabolized by the liver, and increased exposure to LOTRONEX is likely to occur in patients with hepatic impairment. Increased drug exposure may increase the risk of serious adverse reactions. LOTRONEX 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 LOTRONEX Tablets, 0.5 mg (0.562 mg alosetron HCl equivalent to 0.5 mg alosetron), are white, oval, film-coated tablets debossed with GX EX1 on one face. LOTRONEX Tablets, 1 mg (1.124 mg alosetron HCl equivalent to 1 mg alosetron), are blue, oval, film-coated tablets debossed with GX CT1 on one face. Tablets: 0.5 and 1 mg ( 3 )
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 LOTRONEX should not be initiated in patients with constipation [see Warnings and Precautions ( 5.1 )] . 4.2 History of Severe Bowel or Hepatic Disorders LOTRONEX is 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX 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. LOTRONEX 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX for longer than 6 months. LOTRONEX 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 LOTRONEX 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 Sebela at 1-844-732-3521 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 LOTRONEX twice daily for 8 to 24 weeks. The adverse reactions in Table 1 were reported in 1% or more of patients who received LOTRONEX and occurred more frequently on LOTRONEX than on placebo. A statistically significant difference was observed for constipation in patients treated with LOTRONEX compared to placebo (p<0.0001). Table 1. Adverse Reactions Reported in ≥1% of Patients with Irritable Bowel Syndrome and More Frequently on LOTRONEX 1 mg Twice Daily Than Placebo LOTRONEX Body System Placebo 1 mg twice daily Adverse Reaction (n = 2,363) (n = 8,328) Gastrointestinal Constipation 6% 29% Abdominal discomfort and pain 4% 7% Nausea 5% 6% Gastrointestinal discomfort and pain 3% 5% Abdominal distention 1% 2% Regurgitation and reflux 2% 2% Hemorrhoids 1% 2% Gastrointestinal: Constipation is a frequent and dose-related side effect of treatment with LOTRONEX [see Warnings and Precautions ( 5.1 )] . In clinical studies constipation was reported in approximately 29% of patients with IBS treated with LOTRONEX 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 LOTRONEX 1 mg twice daily withdrew from the studies due to constipation. Although the number of patients with IBS treated with LOTRONEX 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX. Hepatic : A similar incidence in elevation of ALT (>2-fold) was seen in patients receiving LOTRONEX 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 LOTRONEX was reported in a 12-week study. A causal association with LOTRONEX 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 LOTRONEX 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 LOTRONEX and occurred more frequently with LOTRONEX than with placebo. Other events reported in 3% or more of patients who received LOTRONEX and occurring more frequently with LOTRONEX 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 LOTRONEX Than Placebo. LOTRONEX LOTRONEX LOTRONEX Adverse Reaction Placebo 0.5 mg once daily 1 mg once daily 1 mg twice daily (n = 176) (n = 175) (n = 172) (n = 176) Constipation 5% 9% 16% 19% Abdominal pain 3% 5% 6% 7% Diarrhea 2% 3% 2% 2% Hemorrhoidal hemorrhage 2% 3% 2% 2% Flatulance 2% 2% 1% 3% Hemorrhoids 2% 1% 1% 3% Abdominal pain upper 1% 3% 1% 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 LOTRONEX and occurring more frequently with LOTRONEX than with placebo included constipation (14% and 10% of patients taking LOTRONEX 1 mg twice daily or 0.5 mg as needed, respectively, compared with 2% taking placebo), abdominal pain, nausea, vomiting, and flatulence. Other events reported in 3% or more of patients who received LOTRONEX and occurring more frequently with LOTRONEX than with placebo included nasopharyngitis, sinusitis, upper respiratory tract infection, urinary tract infection, viral gastroenteritis, and cough.
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 LOTRONEX 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 Alosetron and/or metabolites of alosetron are excreted in the breast milk of lactating rats. It is not known whether alosetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LOTRONEX is administered to a nursing woman. 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 LOTRONEX and any potential adverse effects on the breastfed infant from LOTRONEX or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to LOTRONEX 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 LOTRONEX 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 LOTRONEX is 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX is prescribed for these patients [see Warnings and Precautions ( 5.1 )] .
Overdosage
There is no specific antidote for overdose of LOTRONEX. 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 LOTRONEX [see Drug Interactions ( 7 )].
Description
The active ingredient in LOTRONEX Tablets is alosetron hydrochloride (HCl), a potent and selective antagonist of the serotonin 5-HT 3 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 beige solid that has a solubility of 61 mg/mL in water, 42 mg/mL in 0.1M hydrochloric acid, 0.3 mg/mL in pH 6 phosphate buffer, and <0.1 mg/mL in pH 8 phosphate buffer. The chemical structure of alosetron is: LOTRONEX Tablets are supplied for oral administration as 0.5 mg (white) and 1 mg (blue) tablets. The 0.5 mg tablet contains 0.562 mg alosetron HCl equivalent to 0.5 mg alosetron, and the 1 mg tablet contains 1.124 mg alosetron HCl 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, and triacetin. The blue film coat for the 1 mg tablet contains hypromellose, titanium dioxide, triacetin, and indigo carmine. Chemical Structure
Mechanism of action
12.1 Mechanism of Action Alosetron is a potent and selective 5-HT 3 receptor antagonist. 5-HT 3 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-HT 3 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-HT 3 receptors.
How supplied
Tablets, 0.5 mg (0.562 mg alosetron HCl equivalent to 0.5 mg alosetron) are white, oval, film-coated tablets debossed with GX EX1 on one face. Bottles of 30 (NDC 65483-894-03) with child-resistant closures. LOTRONEX Tablets, 1 mg (1.124 mg alosetron HCl equivalent to 1 mg alosetron), are blue, oval, film-coated tablets debossed with GX CT1 on one face. Bottles of 30 (NDC 65483-895-03) with child-resistant closures. Store at 20-25°C (68-77°F) (USP Controlled Room Temperature). Protect from light and moisture.
Patient information
Advise the patient to read the FDA-approved labeling (Medication Guide). Prescriber and Patient Responsibilities Patients should be fully counseled on and understand the risks and benefits of LOTRONEX before an initial prescription is written. The patient may be educated by the prescriber or a healthcare provider under a prescriber's direction. Patients should be fully counseled on and understand the risks and benefits of LOTRONEX 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 LOTRONEX is appropriate about the benefits and risks of LOTRONEX and discuss the impact of IBS symptoms on the patient's life.counsel patients for whom LOTRONEX is appropriate about the benefits and risks of LOTRONEX and discuss the impact of IBS symptoms on the patient's life. review the Medication Guide, which outlines the benefits and risks of LOTRONEX, and instruct the patient to read it carefully. Answer all questions the patient may have about LOTRONEX. The complete text of the Medication Guide is printed at the end of this document.review the Medication Guide, which outlines the benefits and risks of LOTRONEX, and instruct the patient to read it carefully. Answer all questions the patient may have about LOTRONEX. The complete text of the Medication Guide is printed at the end of this document. provide each patient with appropriate instructions for taking LOTRONEX.provide each patient with appropriate instructions for taking LOTRONEX. Additional copies of the Medication Guide are available by contacting Sebela at 1-844-732-3521 or visiting wwwlotronex.com. Patients who are prescribed LOTRONEX should be instructed to: read the Medication Guide before starting LOTRONEX and each time they refill their prescription.read the Medication Guide before starting LOTRONEX and each time they refill their prescription. not start taking LOTRONEX if they are constipated.not start taking LOTRONEX if they are constipated. immediately discontinue LOTRONEX 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 LOTRONEX. Resume LOTRONEX only if their constipation has resolved and after discussion with and the agreement of their treating prescriber.immediately discontinue LOTRONEX 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 LOTRONEX. Resume LOTRONEX only if their constipation has resolved and after discussion with and the agreement of their treating prescriber. stop taking LOTRONEX and contact their prescriber if LOTRONEX does not adequately control IBS symptoms after 4 weeks of taking 1 mg twice a day.stop taking LOTRONEX and contact their prescriber if LOTRONEX does not adequately control IBS symptoms after 4 weeks of taking 1 mg twice a day. Medication Guide
Label text from the FDA structured product label by Sebela Pharmaceuticals Inc. (revised Jun 30, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Alosetron Hydrochloride in 4 products
Lotronex NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 83107-012 | Alosetron Hydrochloride 1 mg/1 Tablet | Legacy Pharma USA Inc. | NDA |
| 83107-013 | Alosetron Hydrochloride .5 mg/1 Tablet | Legacy Pharma USA Inc. | NDA |
| 54766-894 | Alosetron Hydrochloride .5 mg/1 Tablet | Sebela Pharmaceuticals Inc. | NDA |
| 54766-895 | Alosetron Hydrochloride 1 mg/1 Tablet | Sebela Pharmaceuticals Inc. | NDA |
Frequently asked questions
What is Lotronex used for?
1 INDICATIONS AND USAGE LOTRONEX is 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…
What are the side effects of Lotronex?
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 Lotronex?
Lotronex is listed by 2 labelers in the FDA NDC directory, including Legacy Pharma USA Inc., Sebela Pharmaceuticals Inc..