|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(a LOE se tron)
Generic Available (U.S.)
No
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088624.pdf, must be dispensed with this medication.
REMS Components
Elements to Assure Safe Use; Implementation System; Medication Guide
Prescribing and Access Restrictions
As a requirement of the REMS program, access to the medication is restricted. Physicians must enroll in the Prometheus Prescribing Program for Lotronex® (www.lotronexppl.com or 1-888-423-5227) in order to prescribe this medication. Program stickers must be affixed to all prescriptions; no phone, fax, or computerized prescriptions are permitted with this program.
U.S. Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional therapy
Pregnancy Risk Factor
B
Pregnancy Considerations
There are no adequate and well-controlled studies in pregnant women. Alosetron should be used in pregnant women only if clearly needed.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Animal studies indicate that alosetron and/or metabolites are excreted in breast milk. It is not known if alosetron in excreted in human milk. Caution should be used in administering alosetron to a nursing woman.
Contraindications
Do not start treatment in patients who are constipated. Hypersensitivity to alosetron or any component of the formulation; history of severe or chronic constipation or sequelae from constipation; history of ischemic colitis, intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation and/or adhesions; diverticulitis, current or history of Crohn's disease, or ulcerative colitis; severe hepatic impairment; history of impaired intestinal circulation, thrombophlebitis, or hypercoagulable state; patients unable to understand or comply with “Patient-Physician” agreement; concomitant administration with fluvoxamine
Warnings/Precautions
Boxed warnings:
• Appropriate use: See “Other warnings/precautions” below.
• Constipation: See “Concerns related to adverse effects” below.
• Ischemic colitis: See “Concerns related to adverse effects” below.
• Patient-Physician agreement: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Constipation: [U.S. Boxed Warning]: Discontinue immediately in patients who develop constipation; serious complications of constipation have been infrequently reported (obstruction, ileus, perforation, impaction, toxic megacolon, secondary 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. Do not initiate in patients with constipation.
• Ischemic colitis: [U.S. Boxed Warning]: Acute ischemic colitis has been reported during treatment. Discontinue and evaluate immediately in patients who experience rectal bleeding 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 score ≤9); contraindicated in severe impairment (Child-Pugh score ≥10).
Special populations:
• Elderly: Use with caution in the elderly due to increased risk of complications from constipation.
• Males: Safety and efficacy have not been established in males.
• Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions:
• Appropriate use: [U.S. Boxed Warning]: Only indicated for women with severe diarrhea-predominant irritable bowel syndrome with inadequate response to conventional therapy.
• Patient-Physician agreement: [U.S. Boxed Warning]: Should only be prescribed by physicians enrolled in the Prometheus' Prescribing Program for Lotronex®. Patients must read and sign a “Patient-Physician” agreement before receiving the initial prescription.
Adverse Reactions
>10%: Gastrointestinal: Constipation (dose related; 29%)
2% to 10%: Gastrointestinal: Abdominal discomfort and pain (7%), nausea (6%), gastrointestinal discomfort and pain (5%), abdominal distention (2%), hemorrhoids (2%), regurgitation and reflux (2%)
≤1% (Limited to important or life-threatening): Allergic skin reactions, alopecia, anxiety, arrhythmia, bilirubin level changes, bladder inflammation, bone pain, breathing disorder, cholecystitis, cognitive function disorders, confusion, cramps, colitis, depression, dermatitis, diaphoresis, diverticulitis, dyspepsia, extrasystoles, fatigue, fluid disturbances, gastroenteritis, GI intussusception, GI lesions, GI motility decreased, GI obstructions, GI spasms, hematoma, hemorrhage, hyperacidity, hyper-/hypoglycemia, hypertension, hypnagogic effects, hypoesthesia, hypothalamus/pituitary dysfunction, ileus, ischemic colitis, memory effects, muscle pain/stiffness, occult stools, pain, proctitis, RBC/hemoglobin defects, sedation, sexual dysfunction, skeletal pain, tachyarrhythmia, temperature regulation impairment, tremor, ulcerative colitis, urinary frequency, urticaria
Postmarketing and/or case reports: GI impaction, GI perforation, GI ulceration, headache, hepatitis, rash, small bowel mesenteric ischemia
Metabolism/Transport Effects
Substrate of CYP1A2 (major), 2C9 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 2E1 (weak)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
FluvoxaMINE: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Antiemetics (5HT3 Antagonists). Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: When administered with food, absorption may be reduced by ~25%.
Storage
Store at controlled room temperature of 25°C (77°F).
Mechanism of Action
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.
Pharmacodynamics/Kinetics
Distribution: Vd: 65-95 L
Protein binding: 82%
Metabolism: Extensive hepatic metabolism. Alosetron is metabolized by CYP2C9, 3A4, and 1A2. Thirteen metabolites have been detected in the urine. Biological activity of these metabolites in unknown.
Bioavailability: Mean: 50% to 60% (range: 30% to >90%); decreased with food (25%)
Half-life elimination: 1.5 hours for alosetron
Time to peak: 1 hour after oral administration
Excretion: Urine (73%) and feces (24%); 7% as unchanged drug (1% feces, 6% urine)
Dosage
Oral:
Adults: Female: Initial: 0.5 mg twice daily for 4 weeks, with or without food; if tolerated, but response is inadequate, may be increased after 4 weeks to 1 mg twice daily. If response is inadequate after 4 weeks of 1 mg twice-daily dosing, discontinue treatment.
Note: Discontinue immediately if constipation or signs/symptoms of ischemic colitis occur. Do not reinitiate in patients who develop ischemic colitis.
Elderly: Dosage adjustment is not required; however, postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.
Dosage adjustment in renal impairment: The need for dosage adjustment has not been defined (due to limited information on activity of metabolites).
Dosage adjustment in hepatic impairment: In mild-to-moderate dysfunction (Child-Pugh score ≤9), use caution. Contraindicated in severe hepatic dysfunction (Child-Pugh score ≥10).
Administration: Oral
May be administered with or without food.
Dietary Considerations
May be taken with or without food.
Geriatric Considerations
Postmarketing experience suggests that elderly patients may be at greater risk for complications of constipation.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause depression or sleep abnormalities; may rarely cause anxiety or sedation
Mental Health: Effects on Psychiatric Treatment
Constipation is common; use caution with concurrent psychotropics possessing anticholinergic activity (eg, benztropine, clozapine, TCAs); may cause nausea; concurrent use with SSRIs, lithium, or valproate may produce additive effects
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Lotronex®: 0.5 mg, 1 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Lotronex)
1 mg (30): $428.32
References
Koch KM, Corrigan BW, Manzo J, et al, “Alosetron Repeat Dose Pharmacokinetics, Effects on Enzyme Activities, and Influence of Demographic Factors,” Aliment Pharmacol Ther, 2004, 20(2):223-30.
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
| 
