Alosetron
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]
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Black Box Warning
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WARNING
See full prescribing information for complete Boxed Warning.
SERIOUS GASTROINTESTINAL ADVERSE REACTIONS:
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Overview
Alosetron is a selective serotonin 5-HT3 antagonist that is FDA approved for the {{{indicationType}}} of severe diarrhea-predominant irritable bowel syndrome (IBS). There is a Black Box Warning for this drug as shown here. Common adverse reactions include constipation, abdominal discomfort and pain, nausea, and gastrointestinal discomfort and pain.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Diarrhea-Predominant Irritable Bowel Syndrome
- 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.
- Dosing Information
- 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.
- 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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
- Developed by:
- Class of Recommendation:
- Strength of Evidence:
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Alosetron in adult patients.
Non–Guideline-Supported Use
Condition1
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Alosetron in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
- Dosing Information
- Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Alosetron in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
- Developed by:
- Class of Recommendation:
- Strength of Evidence:
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Alosetron in pediatric patients.
Non–Guideline-Supported Use
Condition1
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Alosetron in pediatric patients.
Contraindications
- Constipation
- LOTRONEX should not be initiated in patients with constipation.
- 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
- LOTRONEX is contraindicated in patients with a history of the following:
- Lack of Understanding of Patient Acknowledgement Form
- LOTRONEX should not be used by patients who are unable to understand or comply with the Patient Acknowledgement Form for LOTRONEX.
- 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.
Warnings
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WARNING
See full prescribing information for complete Boxed Warning.
SERIOUS GASTROINTESTINAL ADVERSE REACTIONS:
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Precautions
- 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].
- 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.
- Prescribing Program for LOTRONEX
- To prescribe LOTRONEX, the prescriber must be enrolled in the Prescribing Program for LOTRONEX. To enroll, prescribers must understand the benefits and risks of treatment with LOTRONEX for severe diarrhea-predominant IBS, including the information in the Prescribing Information, Medication Guide, and Patient Acknowledgement Form for LOTRONEX.
- To enroll in the Prescribing Program for LOTRONEX, call 1-888-423-5227 or visit www.lotronexppl.com to complete the Prescriber Enrollment Form.
Adverse Reactions
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).
T1
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. In Studies 1 and 2, 9% of patients treated with LOTRONEX reported constipation and 4 consecutive days with no bowel movement. 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.
T2
- 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.
- 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 LOTRONEX 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 LOTRONEX 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 LOTRONEX: During its assessment in clinical trials, multiple and single doses of LOTRONEX were administered, resulting in 11,874 subject exposures in 86 completed clinical studies. The conditions, dosages, and duration of exposure to LOTRONEX 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 LOTRONEX, occurred in at least 2 patients, and occurred at a greater frequency during treatment with LOTRONEX 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 LOTRONEX and occurring at a greater frequency in patients treated with LOTRONEX 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 LOTRONEX, 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.
Postmarketing Experience
- In addition to events reported in clinical trials, the following events have been identified during use of LOTRONEX 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 LOTRONEX.
Gastrointestinal
Impaction, perforation, ulceration, small bowel mesenteric ischemia.
Neurological
Headache.
Skin
Rash.
Drug Interactions
- Drug
- Description
Use in Specific Populations
Pregnancy
- Pregnancy Category
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Alosetron in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Alosetron during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Alosetron with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Alosetron with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Alosetron with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Alosetron with respect to specific gender populations.
Race
There is no FDA guidance on the use of Alosetron with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Alosetron in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Alosetron in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Alosetron in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Alosetron in patients who are immunocompromised.
Administration and Monitoring
Administration
- Oral
- Intravenous
Monitoring
There is limited information regarding Monitoring of Alosetron in the drug label.
- Description
IV Compatibility
There is limited information regarding IV Compatibility of Alosetron in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
- Description
Management
- Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Alosetron in the drug label.
Pharmacology
There is limited information regarding Alosetron Pharmacology in the drug label.
Mechanism of Action
Structure
This image is provided by the National Library of Medicine.
Pharmacodynamics
There is limited information regarding Pharmacodynamics of Alosetron in the drug label.
Pharmacokinetics
There is limited information regarding Pharmacokinetics of Alosetron in the drug label.
Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Alosetron in the drug label.
Clinical Studies
There is limited information regarding Clinical Studies of Alosetron in the drug label.
How Supplied
Storage
There is limited information regarding Alosetron Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Patient Counseling Information of Alosetron in the drug label.
Precautions with Alcohol
- Alcohol-Alosetron interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
- ®[1]
Look-Alike Drug Names
- A® — B®[2]
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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