ALOSETRON tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ALOSETRON HYDROCHLORIDE (UNII: 2F5R1A46YW) (ALOSETRON - UNII:13Z9HTH115)

Available from:

Bryant Ranch Prepack

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Alosetron 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, 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 alosetron 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 tablets in men. Alosetron tablets should not be initiated in patients with constipation [see Warnings and Precautions (5.1)] . Alosetron tablets are 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 Concomitant administration of alosetron 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)] . Risk Summary The available data with alosetron tablets use in pregnant women are insufficient to draw conclusions about any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of alosetron in rats and rabbits during organogenesis at doses 160 to 240 times, respectively, the recommended human dosage (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and miscarriage is 15 to 20%, respectively. Data Animal Data No adverse developmental effects were observed with oral administration of alosetron during the period of organogenesis to pregnant rats at doses up to 40 mg/kg/day (about 160 times the recommended human dose based on body surface area) or to pregnant rabbits at doses up to 30 mg/kg/day (about 240 times the recommended daily human dose based on body surface area). Risk Summary There are no data regarding the presence of alosetron in human milk, the effects on the breastfed infant, or the effects on milk production. Alosetron and/or metabolites of alosetron are present in the breast milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk.  The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for alosetron tablets and any potential adverse effects on the breastfed infant from alosetron or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to alosetron through breast milk for severe constipation and blood in stools. Safety and effectiveness in pediatric patients have not been established. Use of alosetron tablets are not recommended in the pediatric population, based upon the risk of serious complications of constipation and ischemic colitis in adults. In some studies, in healthy men or women, plasma concentrations were elevated by approximately 40% in individuals 65 years and older   compared to young adults [see Warnings and Precautions (5.1)] . However, this effect was not consistently observed in men. 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 tablets are prescribed for these patients [see Warnings and Precautions (5.1)] . Due to the extensive hepatic metabolism of alosetron, increased exposure to alosetron and/or its metabolites is likely to occur in patients with hepatic impairment. Alosetron should not be used in patients with severe hepatic impairment and should be used with caution in patients with mild or moderate hepatic impairment. A single 1 mg oral dose of alosetron was administered to 1 female and 5 male patients with moderate hepatic impairment (Child-Pugh score of 7 to 9) and to 1 female and 2 male patients with severe hepatic impairment (Child-Pugh score of >9). In comparison with historical data from healthy subjects, patients with severe hepatic impairment displayed higher systemic exposure to alosetron. The female with severe hepatic impairment displayed approximately 14-fold higher exposure, while the female with moderate hepatic impairment displayed approximately 1.6-fold higher exposure, than healthy females. Due to the small number of subjects and high intersubject variability in the pharmacokinetic findings, no definitive quantitative conclusions can be made. However, due to the greater exposure to alosetron in the female with severe hepatic impairment, alosetron should not be used in females with severe hepatic impairment [see Dosage and Administration (2.2), Contraindications (4)] . Renal impairment (creatinine clearance 4 to 56 mL/min) has no effect on the renal elimination of alosetron due to the minor contribution of this pathway to elimination. The effect of renal impairment on metabolite pharmacokinetics and the effect of end-stage renal disease have not been assessed.

Product summary:

Alosetron Tablets USP, 1 mg (1.124 mg alosetron HCl equivalent to 1 mg alosetron), are round, film coated, blue colored biconvex tablets debossed with "LS 701" on one side and plain on other side. Bottles of 30 (NDC 63629-2518-1) with child-resistant closures. Store at 20-25°C (68-77°F) (See USP Controlled Room Temperature). Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Bryant Ranch Prepack
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MEDICATION GUIDE
Alosetron (a-LOE-se-tron) Tablets, USP
Read the Medication Guide you get with each refill for alosetron
tablets. There may be new information.
This Medication Guide does not take the place of talking with your
doctor.
What is the most important information I should know about alosetron
tablets?
Alosetron tablets are medicine only for some women with severe chronic
irritable bowel syndrome (IBS)
whose:
● main problem is diarrhea and
● IBS symptoms have not been helped enough by other treatments.
Some people have developed serious bowel side effects while taking
alosetron tablets. Serious bowel
(intestine) side effects can happen suddenly, including the following:
● Serious complications of constipation:
These complications may lead to a hospital stay and, in rare cases,
blood transfusions, surgery, and death.
People who are older, who are weak from illness, or who take other
constipating medicines may be more
likely to have serious complications of constipation with alosetron
tablets.
● To lower your chances of getting serious complications of
constipation, do the following:
○ If you are constipated, do not start taking alosetron tablets
○ If you get constipated while taking alosetron tablets, stop taking
it right away and call your
doctor.
○ If your constipation does not get better after stopping alosetron
tablets, call your doctor
again.
○ If you stopped taking alosetron tablets, do not start taking
alosetron tablets again unless
your doctor tells you to do so.
● Inflammation and injury of the intestines caused by reduced blood
flow (ischemic colitis: Ischemic
colitis is caused by reduced blood flow to parts of the large bowel.
The chance of getting ischemic colitis
when you take alosetron tablets for more than 6 months is not known.
Ischemic colitis may lead to a
hospital stay and, in rare cases, blood transfusions, surgery, and
death.
Stop taking alosetron tablets and call your doctor or get medical help
if you have symptoms of ischemic
colitis

Summary of Product characteristics

ALOSETRON- ALOSETRON TABLET
BRYANT RANCH PREPACK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ALOSETRON TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ALOSETRON
TABLETS.
ALOSETRON TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2000
WARNING: SERIOUS GASTROINTESTINAL ADVERSE REACTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INFREQUENT BUT SERIOUS GASTROINTESTINAL ADVERSE REACTIONS HAVE BEEN
REPORTED WITH THE
USE OF ALOSETRON TABLETS. THESE EVENTS, INCLUDING ISCHEMIC COLITIS AND
SERIOUS
COMPLICATIONS OF CONSTIPATION, HAVE RESULTED IN HOSPITALIZATION AND,
RARELY, BLOOD
TRANSFUSION, SURGERY, AND DEATH.
ALOSETRON TABLETS ARE INDICATED ONLY FOR WOMEN WITH SEVERE
DIARRHEA-PREDOMINANT
IRRITABLE BOWEL SYNDROME (IBS) WHO HAVE NOT RESPONDED ADEQUATELY TO
CONVENTIONAL
THERAPY. (1)
DISCONTINUE ALOSETRON TABLETS IMMEDIATELY IN PATIENTS WHO DEVELOP
CONSTIPATION OR
SYMPTOMS OF ISCHEMIC COLITIS. DO NOT RESUME ALOSETRON TABLETS IN
PATIENTS WHO
DEVELOP ISCHEMIC COLITIS. (2.1, 5.1, 5.2)
INDICATIONS AND USAGE
Alosetron tablets are selective serotonin 5-HT antagonist 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. (1)
Severe IBS includes diarrhea and 1 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. (1)
DOSAGE AND ADMINISTRATION
Starting dose is 0.5 mg twice a day (2.1)
May increase dose to 1 mg twice a day after 4 weeks if starting dosage
is well tolerated but does not
adequately control IBS symptoms (2.1)
Discontinue alosetron tablets in patients who have not had adequate
control of IBS symptoms after 4
weeks of treatment with 1 mg twice a day. (2.1)
DO