NDC 64980-454 Alosetron Hyochloride

Alosetron Hyochloride

NDC Product Code 64980-454

NDC Code: 64980-454

Proprietary Name: Alosetron Hyochloride Additional informationCallout TooltipWhat is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Alosetron Hyochloride Additional informationCallout TooltipWhat is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.


Product Characteristics
Color(s):
WHITE (C48325)
BLUE (C48333)
Shape: OVAL (C48345)
Size(s):
11 MM
Imprint(s):
CIPLA;198
CIPLA;199
Score: 1

Code Structure
  • 64980 - Rising Pharmaceuticals, Inc.
    • 64980-454 - Alosetron Hyochloride

NDC 64980-454-03

Package Description: 30 TABLET in 1 BOTTLE

NDC 64980-454-50

Package Description: 500 TABLET in 1 BOTTLE

NDC Product Information

Alosetron Hyochloride with NDC 64980-454 is a a human prescription drug product labeled by Rising Pharmaceuticals, Inc.. The generic name of Alosetron Hyochloride is alosetron hyochloride. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Rising Pharmaceuticals, Inc.

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug Additional informationCallout TooltipWhat kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.


Alosetron Hyochloride Active Ingredient(s)

Additional informationCallout TooltipWhat is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • ALOSETRON HYDROCHLORIDE 1 mg/1

Inactive Ingredient(s)

Additional informationCallout TooltipAbout the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • LACTOSE (UNII: J2B2A4N98G)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • HYPROMELLOSE 2910 (6 MPA.S) (UNII: 0WZ8WG20P6)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • TRIACETIN (UNII: XHX3C3X673)
  • LACTOSE (UNII: J2B2A4N98G)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • HYPROMELLOSE 2910 (6 MPA.S) (UNII: 0WZ8WG20P6)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • TRIACETIN (UNII: XHX3C3X673)
  • INDIGOTINDISULFONATE SODIUM (UNII: D3741U8K7L)

Administration Route(s)

Additional informationCallout TooltipWhat are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

Additional informationCallout TooltipWhat is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Serotonin 3 Receptor Antagonists - [MoA] (Mechanism of Action)
  • Serotonin-3 Receptor Antagonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

Additional informationCallout TooltipWhat is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Rising Pharmaceuticals, Inc.
Labeler Code: 64980
FDA Application Number: ANDA209180 Additional informationCallout TooltipWhat is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. Additional informationCallout TooltipWhat is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 01-14-2019 Additional informationCallout TooltipWhat is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 Additional informationCallout TooltipWhat is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N Additional informationCallout TooltipWhat is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Alosetron Hyochloride Product Label Images

Alosetron Hyochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Warning: Serious Gastrointestinal Adverse Reactions

  • Infrequent but serious gastrointestinal adverse reactions have been reported with the use of alosetron hydrochloride tablets. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalization, and rarely, blood transfusion, surgery, and death.Alosetron hydrochloride tablets are indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have not responded adequately to conventional therapy [see Indications and Usage (1)] .Alosetron hydrochloride tablets should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Patients should immediately report constipation or symptoms of ischemic colitis to their prescriber. Alosetron hydrochloride tablets should not be resumed in patients who develop ischemic colitis. Patients who have constipation should immediately contact their prescriber if the constipation does not resolve after alosetron hydrochloride tablets are discontinued. Patients with resolved constipation should resume alosetron hydrochloride tablets only on the advice of their treating prescriber [see Dosage and Administration (2.1), Warnings and Precautions (5.1), (5.2)].

1. Indications And Usage

  • Alosetron hydrochloride 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, andnot 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 hydrochloride 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 hydrochloride tablets in men.

2.1 Adult Patients

To lower the risk of constipation, alosetron hydrochloride 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 hydrochloride tablets until the constipation resolves. They may be restarted at 0.5 mg once a day. If constipation recurs at the lower dose, alosetron hydrochloride 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 hydrochloride 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 hydrochloride tablets can be taken with or without food [see Clinical Pharmacology (12.3)]. Alosetron hydrochloride tablets should be discontinued immediately in patients who develop constipation or signs of ischemic colitis. Alosetron hydrochloride 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 hydrochloride 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 hydrochloride tablets are prescribed for these patients [see Warnings and Precautions (5.1)].

2.2 Patients With Hepatic Impairment

Alosetron is extensively metabolized by the liver, and increased exposure to alosetron is likely to occur in patients with hepatic impairment. Increased drug exposure may increase the risk of serious adverse reactions. Alosetron hydrochloride 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)].

3. Dosage Forms And Strengths

Alosetron HCl Tablet, 0.5 mgWhite to off white colored, oval, biconvex, film coated tablet debossed with "Cipla" on one side and "198" on the other side.Alosetron HCl Tablet, 1 mgBlue colored, oval, biconvex, film coated tablet debossed with "Cipla" on one side and "199" on the other side.

4.1 Constipation

Alosetron hydrochloride 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 hydrochloride tablets are contraindicated in patients with a history of the following: chronic or severe constipation or sequelae from constipationintestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and/or adhesionsischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable stateCrohn's disease or ulcerative colitisdiverticulitissevere hepatic impairment

4.3 Concomitant Use Of Fluvoxamine

Concomitant administration of alosetron hydrochloride 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)].

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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride tablets for longer than 6 months. Alosetron hydrochloride 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 hydrochloride tablets should not be resumed in patients who develop ischemic colitis.

6. Adverse Reactions

  • 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)]

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 hydrochloride 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 hydrochloride tablets and occurred more frequently on alosetron hydrochloride tablets than on placebo. A statistically significant difference was observed for constipation in patients treated with alosetron hydrochloride 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 Hydrochloride Tablets 1 mg Twice Daily Than Placebo
Body System Adverse Reaction Placebo (n = 2,363) Alosetron Hydrochloride 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 hydrochloride tablets [see Warnings and Precautions (5.1)]. In clinical studies constipation was reported in approximately 29% of patients with IBS treated with alosetron hydrochloride 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 hydrochloride tablets 1 mg twice daily withdrew from the studies due to constipation. Although the number of patients with IBS treated with alosetron hydrochloride 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 hydrochloride 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 hydrochloride 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 hydrochloride tablets. Hepatic: A similar incidence in elevation of ALT (>2-fold) was seen in patients receiving alosetron hydrochloride 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 hydrochloride tablets was reported in a 12-week study. A causal association with alosetron hydrochloride tablets have 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 hydrochloride 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 hydrochloride tablets and occurred more frequently with alosetron hydrochloride tablets than with placebo. Other events reported in 3% or more of patients who received alosetron hydrochloride tablets and occurring more frequently with alosetron hydrochloride 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 Hydrochloride Tablets Than Placebo .
Adverse Reaction Placebo Alosetron Hydrochloride Tablets 0.5 mg once daily Alosetron Hydrochloride Tablets 1 mg once daily Alosetron Hydrochloride Tablets 1 mg twice daily (n = 176) (n = 175) (n = 172) (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 hydrochloride tablets and occurring more frequently with alosetron hydrochloride tablets than with placebo included constipation (14% and 10% of patients taking alosetron hydrochloride tablets 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 alosetron hydrochloride tablets and occurring more frequently with alosetron hydrochloride tablets than with placebo included nasopharyngitis, sinusitis, upper respiratory tract infection, urinary tract infection, viral gastroenteritis, and cough. Constipation: Constipation was the most frequent adverse reaction among women with severe diarrhea-predominant IBS represented in Table 2. There was a dose response in the groups treated with alosetron hydrochloride tablets in the number of patients withdrawn due to constipation (2% on placebo, 5% on 0.5 mg once daily, 8% on 1 mg once daily, and 11% on 1 mg twice daily). Among these patients with severe diarrhea-predominant IBS treated with alosetron hydrochloride tablets who reported constipation most (75%) reported one episode which occurred within the first 15 days of treatment and persisted for 4 to 5 days. Other Events Observed During Clinical Evaluation of Alosetron Hydrochloride Tablets: During its assessment in clinical trials, multiple and single doses of alosetron hydrochloride tablets were administered, resulting in 11,874 subject exposures in 86 completed clinical studies. The conditions, dosages, and duration of exposure to alosetron hydrochloride tablets varied between trials, and the studies included healthy male and female volunteers as well as male and female patients with IBS and other indications. In the listing that follows, reported adverse reactions were classified using a standardized coding dictionary. Only those events that an investigator believed were possibly related to alosetron hydrochloride tablets, occurred in at least 2 patients, and occurred at a greater frequency during treatment with alosetron hydrochloride tablets than during placebo administration are presented. Serious adverse reactions occurring in at least 1 patient for whom an investigator believed there was reasonable possibility that the event was related to treatment with alosetron hydrochloride tablets and occurring at a greater frequency in patients treated with alosetron hydrochloride tablets than placebo-treated patients are also presented. In the following listing, events are categorized by body system. Within each body system, events are presented in descending order of frequency. The following definitions are used: infrequent adverse reactions are those occurring on one or more occasion in 1/100 to 1/1,000 patients; rare adverse reactions are those occurring on one or more occasion in fewer than 1/1,000 patients. Although the events reported occurred during treatment with alosetron hydrochloride tablets, they were not necessarily caused by it. Blood and Lymphatic: Rare: Quantitative red cell or hemoglobin defects, and hemorrhage. Cardiovascular: Infrequent: Tachyarrhythmias. Rare: Arrhythmias, increased blood pressure, and extrasystoles. Drug Interaction, Overdose, and Trauma: Rare: Contusions and hematomas. Ear, Nose, and Throat: Rare: Ear, nose, and throat infections; viral ear, nose, and throat infections; and laryngitis. Endocrine and Metabolic: Rare: Disorders of calcium and phosphate metabolism, hyperglycemia, hypothalamus/pituitary hypofunction, hypoglycemia, and fluid disturbances. Eye: Rare: Light sensitivity of eyes. Gastrointestinal: Infrequent: Hyposalivation, dyspeptic symptoms, gastrointestinal spasms, ischemic colitis [see Warnings and Precautions (5.2)], and gastrointestinal lesions. Rare: Abnormal tenderness, colitis, gastrointestinal signs and symptoms, proctitis, diverticulitis, positive fecal occult blood, hyperacidity, decreased gastrointestinal motility and ileus, gastrointestinal obstructions, oral symptoms, gastrointestinal intussusception, gastritis, gastroduodenitis, gastroenteritis, and ulcerative colitis. Hepatobiliary Tract and Pancreas: Rare: Abnormal bilirubin levels and cholecystitis. Lower Respiratory: Infrequent: Breathing disorders. Musculoskeletal: Rare: Muscle pain; muscle stiffness, tightness and rigidity; and bone and skeletal pain. Neurological: Infrequent: Hypnagogic effects. Rare: Memory effects, tremors, dreams, cognitive function disorders, disturbances of sense of taste, disorders of equilibrium, confusion, sedation, and hypoesthesia.Non-Site Specific: Infrequent: Malaise and fatigue, cramps, pain, temperature regulation disturbances. Rare: Burning sensations, hot and cold sensations, cold sensations, and fungal infections. Psychiatry: Infrequent: Anxiety. Rare: Depressive moods. Reproduction: Rare: Sexual function disorders, female reproductive tract bleeding and hemorrhage, reproductive infections, and fungal reproductive infections. Skin: Infrequent: Sweating and urticaria. Rare: Hair loss and alopecia; acne and folliculitis; disorders of sweat and sebum; allergic skin reaction; eczema; skin infections; dermatitis and dermatosis; and nail disorders. Urology: Infrequent: Urinary frequency. Rare: Bladder inflammation; polyuria and diuresis; and urinary tract hemorrhage.

6.2 Postmarketing Experience

In addition to events reported in clinical trials, the following events have been identified during use of alosetron hydrochloride tablets in clinical practice. Because they were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to alosetron hydrochloride tablets. Gastrointestinal: Impaction, perforation, ulceration, small bowel mesenteric ischemia. Neurological: Headache. Skin: Rash.

7. 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.

7.1 Cyp1a2 Inhibitors