Version May 2024
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.
Irritable bowel syndrome with diarrhea, severe (alternative agent):
Note: Safety: Due to risk of serious adverse effects (eg, ischemic colitis), reserve for female patients with severe diarrhea-predominant irritable bowel syndrome symptoms for >6 months who have had an inadequate response to conventional treatments (Ref). Patient should be under the care of a clinician experienced with use of alosetron.
Standard dose: Oral: Initial: 0.5 mg twice daily; if patient becomes constipated at 0.5 mg twice daily, discontinue therapy until constipation resolves. May restart at 0.5 mg once daily. If constipation recurs at 0.5 mg once daily, permanently discontinue (Ref).
Dosage titration : If 0.5 mg twice daily is tolerated but response is inadequate after 4 weeks, may increase to 1 mg twice daily (maximum dose: 2 mg/day). If response is inadequate after 4 weeks at 1 mg twice-daily dosing, discontinue treatment (Ref).
Low dose: Oral: Due to safety concerns with standard dosing, some experts recommend initiating at 0.5 mg once daily (Ref).
Dosage titration : After 4 weeks, increase dose only if needed to 0.5 mg twice daily; if response is inadequate after 4 weeks at 0.5 mg twice-daily dosing and patient is tolerating, may increase to 1 mg twice daily (maximum: 2 mg/day) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
Mild to moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer's labeling; use with caution due to extensive metabolism and increased drug exposure.
Severe impairment (Child-Pugh class C): Use is contraindicated.
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
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%: Gastrointestinal: Constipation (9% to 29%; dose related)
1% to 10%:
Cardiovascular: Tachyarrhythmia (≤1%)
Dermatologic: Diaphoresis (≤1%), urticaria (≤1%)
Gastrointestinal: Abdominal distention (2%), abdominal distress (≤7%), abdominal pain (5% to 7%; upper abdominal pain: 3%), active gastrointestinal lesion (≤1%), dyspepsia (≤1%), flatulence (3%), gastrointestinal distress (≤5%), gastrointestinal pain (≤5%), gastrointestinal spasm (≤1%), hemorrhoidal bleeding (3%), hemorrhoids (2% to 3%), ischemic colitis (≤1%), nausea (6%), viral gastroenteritis (≥3%), vomiting (≥3%), xerostomia (≤1%)
Genitourinary: Urinary frequency (≤1%), urinary tract infection (≥3%)
Nervous system: Anxiety (≤1%), disruption of body temperature regulation (≤1%), drowsiness (≤1%), fatigue (≥3%), headache (≥3%), malaise (≤1%), pain (≤1%)
Neuromuscular & skeletal: Muscle cramps (≤1%), muscle spasm (≥3%)
Respiratory: Cough (≥3%), nasopharyngitis (≥3%), sinusitis (≥3%), upper respiratory tract infection (≥3%)
<1%:
Cardiovascular: Cardiac arrhythmia, extrasystoles, increased blood pressure
Dermatologic: Acne vulgaris, allergic skin reaction, alopecia, dermatitis, eczema, folliculitis, nail disease, seborrheic dermatitis, skin infection, sweat gland disease
Endocrine & metabolic: Abnormal serum calcium, fluid volume disorder, HPA-axis suppression, hyperglycemia, hypoglycemia, phosphate imbalance, pituitary insufficiency
Gastrointestinal: Abdominal tenderness, cholecystitis, colitis, decreased gastrointestinal motility, diverticulitis of the gastrointestinal tract, duodenitis, dysgeusia, gastric hyperacidity, gastritis, gastroenteritis, gastrointestinal obstruction, intestinal intussusception, intestinal obstruction, occult blood in stools, oral changes, proctitis, ulcerative colitis
Genitourinary: Cystitis, diuresis, gynecological bleeding, sexual disorder, urinary tract hemorrhage
Hematologic & oncologic: Abnormal erythrocytes, bruise, hematoma, hemoglobinopathy, hemorrhage
Hepatic: Abnormal bilirubin levels, hepatitis
Infection: Infection (fungal infection, reproductive infection, and fungal reproductive infection)
Nervous system: Balance impairment, burning sensation, cognitive dysfunction, confusion, depressed mood, feeling hot, hypertonia, hypoesthesia, increased dream activity, memory impairment, sedated state, sensation of cold, tremor
Neuromuscular & skeletal: Muscle rigidity, myalgia, ostealgia, skeletal pain
Ophthalmic: Photophobia
Renal: Polyuria
Respiratory: ENT infection (including viral ENT infection), laryngitis
Postmarketing:
Dermatologic: Skin rash
Gastrointestinal: Fecal impaction (Krause 2007), gastrointestinal perforation, gastrointestinal ulcer, mesenteric ischemia (small bowel)
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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
• Older adult: 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.
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
Yes
Tablets (Alosetron HCl Oral)
0.5 mg (per each): $29.45 - $34.45
1 mg (per each): $58.90 - $68.91
Tablets (Lotronex Oral)
0.5 mg (per each): $50.86
1 mg (per each): $101.73
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: May be administered with or without food.
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.
Irritable bowel syndrome, with diarrhea, severe: Treatment of females with severe diarrhea-predominant irritable bowel syndrome (IBS-D) 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.
Lotronex may be confused with Lovenox, Protonix
Substrate of CYP1A2 (major), CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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. Risk D: Consider therapy modification
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Alosetron. Risk C: Monitor therapy
Eluxadoline: Alosetron may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
FluvoxaMINE: May decrease the metabolism of Alosetron. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: 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. Risk C: Monitor therapy
Tobacco (Smoked): May decrease the serum concentration of Alosetron. Risk C: 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. Risk C: Monitor therapy
When administered with food, absorption may be reduced by ~25%. Management: May administer without regard to meals.
Adverse events have not been observed in animal reproduction studies.
It is not known if alosetron is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; monitor infants for severe constipation or blood in stools.
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
Protein binding: 82%
Metabolism: Extensive hepatic metabolism via 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
Time to peak: 1 hour
Excretion: Urine (74%, 13% of total dose as unchanged drug); feces (11%, 1% of total dose as unchanged drug)
Hepatic function impairment: Exposure to alosetron is increased.
Older adult: Plasma levels are elevated by about 40% in patients 65 years and older.
Sex: Plasma concentrations are 30% to 50% lower and less variable in men
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