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Alosetron

Medically reviewed by Drugs.com. Last updated on Apr 25, 2020.

Pronunciation

(a LOE se tron)

Index Terms

  • Alosetron HCl

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lotronex: 0.5 mg, 1 mg

Generic: 0.5 mg, 1 mg

Brand Names: U.S.

  • Lotronex

Pharmacologic Category

  • Selective 5-HT3 Receptor Antagonist

Pharmacology

Alosetron is a potent and selective antagonist of a subtype of the serotonin 5-HT3 receptor. 5-HT3 receptors are ligand-gated ion channels extensively distributed on enteric neurons in the human gastrointestinal tract, as well as other peripheral and central locations. Activation of these channels affect the regulation of visceral pain, colonic transit, and gastrointestinal secretions. In patients with irritable bowel syndrome, blockade of these channels may reduce pain, abdominal discomfort, urgency, and diarrhea.

Absorption

Rapid

Distribution

Vd: 65 to 95 L

Metabolism

Extensive hepatic metabolism via CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.

Excretion

Urine (74%, 13% of total dose as unchanged drug); feces (11%, 1% of total dose as unchanged drug)

Time to Peak

1 hour

Half-Life Elimination

1.5 hours

Protein Binding

82%

Special Populations: Hepatic Function Impairment

Exposure to alosetron is increased.

Special Populations: Elderly

Plasma levels are elevated by about 40% in patients 65 years and older.

Special Populations: Gender

Plasma concentrations are 30% to 50% lower and less variable in men.

Use: Labeled Indications

Irritable bowel syndrome: Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have chronic IBS symptoms (generally lasting 6 months or longer), have had anatomic or biochemical abnormalities of the GI tract excluded, and who have not responded adequately to conventional therapy.

Contraindications

Do not initiate in patients with constipation. History of chronic or severe constipation or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, GI perforation, adhesions, diverticulitis, Crohn disease, ulcerative colitis, history of severe hepatic impairment; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; coadministration with fluvoxamine.

Dosing: Adult

Irritable bowel syndrome (IBS): Females: Oral: Initial: 0.5 mg twice daily for 4 week; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily (maximum dose: 2 mg/day). If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing. Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.

Dosing: Adjustment for Toxicity

Constipation: Patients experiencing constipation with 0.5 mg twice daily should discontinue therapy until constipation resolves. Therapy may be reinitiated at 0.5 mg once daily. Discontinue immediately if constipation recurs at lower dose.

Ischemic colitis: Discontinue therapy immediately; do not restart

Administration

May be administered with or without food.

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Drug Interactions

Abametapir: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Avoid combination

Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Avoid combination

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Monitor therapy

Eluxadoline: Alosetron may enhance the constipating effect of Eluxadoline. Avoid combination

FluvoxaMINE: May decrease the metabolism of Alosetron. Avoid combination

Serotonergic Agents (High Risk): Alosetron may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: FluvoxaMINE; TraMADol. Monitor therapy

Tobacco (Smoked): May decrease the serum concentration of Alosetron. Monitor therapy

TraMADol: Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Adverse Reactions

>10%: Gastrointestinal: Constipation (9% to 29%; dose related)

1% to 10%:

Central nervous system: Fatigue (≥3%), headache (≥3%)

Gastrointestinal: Abdominal distress (≤1% to 7%), abdominal pain (≤1% to 7%), nausea (6%), gastrointestinal distress (≤5%), gastrointestinal pain (≤5%), gastroenteritis (≥3%), vomiting (≥3%), diarrhea (2% to 3%), flatulence (1% to 3%), hemorrhoids (1% to 3%), abdominal distention (2%), acid regurgitation (≤2%), gastroesophageal reflux disease (≤2%)

Genitourinary: Urinary tract infection (≥3%)

Neuromuscular & skeletal: Muscle spasm (≥3%)

Respiratory: Cough (≥3%), nasopharyngitis (≥3%), upper respiratory tract infection (≥3%)

<1%, postmarketing, and/or case reports: Abnormal bilirubin levels, abnormal erythrocytes, active gastrointestinal lesion, allergic skin reaction, alopecia, anxiety, cardiac arrhythmia, cholecystitis, cognitive dysfunction, colitis, confusion, cystitis, decreased gastrointestinal motility, depression, dermatitis, diaphoresis, disruption of body temperature regulation, disturbance in fluid balance, diverticulitis, drowsiness, dyspepsia, extrasystoles, fecal impaction, gastrointestinal obstruction, gastrointestinal perforation, gastrointestinal spasm, gastrointestinal ulcer, hematoma, hemoglobinopathy, hemorrhage, hepatitis, hyperacidity, hyperglycemia, hypertension, hypoesthesia, hypoglycemia, hypothalamic disease, intestinal obstruction, intussusception, ischemic colitis, memory impairment, mesenteric ischemia (small bowel), muscle cramps, muscle rigidity, myalgia, occult blood in stools, ostealgia, pain, pituitary insufficiency, proctitis, respiratory tract disease, sedation, sexual disorder, skeletal pain, skin rash, tachyarrhythmia, tremor, ulcerative colitis, urinary frequency, urticaria

ALERT: U.S. Boxed Warning

Serious GI adverse reactions:

Infrequent but serious GI adverse reactions have been reported with the use of alosetron. These reactions, including ischemic colitis and serious complications of constipation, have resulted in hospitalization, and, rarely, blood transfusion, surgery, and death.

Alosetron is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have not responded adequately to conventional therapy.

Alosetron 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 health care provider. Alosetron should not be resumed in patients who develop ischemic colitis. Patients who have constipation should immediately contact their health care provider if the constipation does not resolve after alosetron is discontinued. Patients with resolved constipation should resume alosetron only on the advice of their treating health care provider.

Warnings/Precautions

Concerns related to adverse effects:

• Constipation: [US Boxed Warning]: Discontinue immediately in patients who develop constipation; infrequent but serious complications of constipation, have resulted in hospitalization, and rarely, blood transfusion, surgery, or death have been reported (obstruction, ileus, perforation [rare], impaction, toxic megacolon, secondary bowel ischemia). Constipation is a frequent, dose-related side effect; risk for complications from constipation may be increased in elderly, debilitated patients, or with concurrent use of other medications which decrease GI motility. Nonsevere constipation may be managed by temporarily interrupting therapy and decreasing the dose. Do not initiate in patients with constipation.

• Ischemic colitis: [US Boxed Warning]: Ischemic colitis has been reported during treatment without warning. Discontinue and evaluate immediately in patients who experience rectal bleeding, bloody diarrhea, or a sudden worsening of abdominal pain, and do not restart therapy if ischemic colitis is diagnosed.

Disease-related concerns:

• Hepatic impairment: Use caution in mild to moderate hepatic impairment (Child-Pugh class A or B) (extensively metabolized); contraindicated in severe impairment (Child-Pugh class C).

Special populations:

• Debilitated patients: Use with caution in debilitated patients due to increased risk of complications from constipation.

• Elderly: Use with caution in the elderly due to increased risk of complications from constipation.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome who have not responded adequately to conventional therapy who have chronic IBS symptoms (lasting ≥6 months) and are without anatomic or biochemical abnormalities of the GI tract. Severe diarrhea-predominant IBS includes at least one of the following: frequent and severe abdominal pain/discomfort, frequent bowel urgency or fecal incontinence, and disability or restriction of daily activities due to IBS.

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat irritable bowel syndrome.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Abdominal pain

• Nausea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Gastrointestinal problems like constipation, new or severe abdominal pain, or blood in stools

• Bloating

• Mood changes

• Rectal bleeding

• Vomiting

• Fast heartbeat

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.