Alosetron

Name: Alosetron

Why is this medication prescribed?

Alosetron is used to treat diarrhea, pain, cramps, and the feeling of an urgent need to have bowel movements caused by irritable bowel syndrome (IBS; a condition that causes stomach pain, bloating, constipation, and diarrhea) in women who have diarrhea as their main symptom and have not been helped by other treatments. Alosetron is in a class of medications called 5-HT3 receptor antagonists. Alosetron works by slowing the movement of stool (bowel movements) through the intestines.

Alosetron Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Serious or fatal side effects on the stomach and intestines have occurred in some people taking alosetron. In rare cases, alosetron has caused severe constipation, or ischemic colitis (caused by reduced blood flow to the intestines).

Stop taking alosetron and call your doctor right away if you develop:

  • new or worsening constipation;
  • stomach pain;
  • bright or dark red blood in your stools; or
  • bloody diarrhea.

You may need to permanently discontinue alosetron if you have these side effects.

Older adults and those who are ill or debilitated may be more likely to have serious complications from constipation.

Common side effects may include:

  • constipation;
  • nausea; or
  • pain or discomfort in your stomach or intestines.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What else should I know about alosetron?

What preparations of alosetron are available?

Tablet: 0.5 and 1 mg.

How should I keep alosetron stored?

Tablets should be stored at room temperature, 15 C to 30 C (59 F to 86 F).

Alosetron Brand Names

Alosetron may be found in some form under the following brand names:

  • Lotronex

Alosetron Interactions

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Alosetron and other medicines may affect each other. Always check with your doctor before starting or stopping any medicines. Especially tell your doctor if you take:

  • antihistamines
  • certain antidepressants ('mood elevators') called tricyclic antidepressants
  • certain medications to treat asthma, diarrhea, lung disease, mental illness, motion sickness, overactive bladder, pain, Parkinson's disease, stomach or intestinal cramps, ulcers and upset stomach

Also, be sure to mention to your doctor if you take:

  • amiodarone (Cordarone, Pacerone)
  • certain antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend)
  • aprepitant (Emend)
  • cimetidine (Tagamet)
  • clarithromycin (Biaxin, in Prevpac)
  • cyclosporine (Neoral, Sandimmune)
  • diltiazem (Cardizem, Dilacor, Tiazac, others)
  • erythromycin (E.E.S., E-Mycin, Erythrocin)
  • fluoroquinolone antibiotics including ciprofloxacin (Cipro), gatifloxacin (Tequin), levofloxacin (Levaquin), norfloxacin (Noroxin), ofloxacin (Floxin), others
  • fluoxetine (Prozac, Sarafem)
  • hormonal contraceptives (birth control pills, implants, injections, rings, and patches)
  • hydralazine
  • isoniazid (INH, Nydrazid)
  • lovastatin (Advicor, Altocor, Mevacor)
  • certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase, Invirase)
  • nefazodone
  • procainamide (Procanbid, Pronestyl)
  • sertraline (Zoloft)
  • telithromycin (Ketek)
  • ticlopidine (Ticlid)
  • troleandomycin (TAO)
  • verapamil (Calan, Covera, Isoptin, Verelan)
  • zafirlukast (Accolate)

Pregnancy & Lactation

Pregnancy Category: B

Lactation: Not known whether drug distributed into breast milk, use caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Proper Use of alosetron

Read the Medication Guide before starting alosetron for the first time and each time you refill your alosetron prescription.

Your doctor will ask you to sign a Patient-Physician Agreement after you have read the Medication Guide for the first time. Signing the agreement means that you understand the risks and benefits of alosetron therapy and that you have read and understand the Medication Guide.

Your doctor will tell you how much of alosetron to use and how often. Do not start taking alosetron if you are constipated. Do not use more medicine or use it more often than your doctor tells you to.

alosetron may be taken with or without food.

Dosing

The dose of alosetron will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of alosetron. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For irritable bowel syndrome (IBS):
      • Adults—At first, 0.5 milligram (mg) twice a day for 4 weeks. Your doctor may increase your dose to 1 mg twice a day for another 4 weeks.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of alosetron, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using alosetron

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Stop taking alosetron and check with your doctor right away if you become constipated or have symptoms of poor blood flow to your bowels (ischemic colitis). Some symptoms of poor blood flow are: new or worsening abdominal pain, bloody diarrhea, or blood in the stool.

Do not start taking alosetron again unless your doctor tells you to do so.

Do not take alosetron if you are also using fluvoxamine (Luvox®).

What are some things I need to know or do while I take Alosetron?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • It may take 1 month to see the full effect.
  • If you are 65 or older, use alosetron with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Alosetron) best taken?

Use alosetron as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • Take this medicine at the same time of day.

What do I do if I miss a dose?

  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

How do I store and/or throw out Alosetron?

  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Dosage Forms and Strengths

0.5 mg and 1 mg tablets

Alosetron hydrochloride tablets, 0.5 mg (0.562 mg Alosetron hydrochloride equivalent to 0.5 mg Alosetron), are white, oval shaped, film-coated tablets debossed with “AN248” on one side and plain on the other side.

Alosetron hydrochloride tablets, 1 mg (1.124 mg Alosetron hydrochloride equivalent to 1 mg Alosetron), are light blue, oval shaped, film-coated tablets debossed with “AN249” on one side and plain on the other side.

Nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In 2-year oral studies, Alosetron was not carcinogenic in mice at doses up to 30 mg/kg/day or in rats at doses up to 40 mg/kg/day. These doses are about 60 to 160 times, respectively, the recommended human dose of Alosetron of 2 mg/day (1 mg twice daily) based on body surface area. Alosetron was not genotoxic in the Ames tests, the mouse lymphoma cell (L5178Y/TK±) forward gene mutation test, the human lymphocyte chromosome aberration test, the ex vivo rat hepatocyte unscheduled DNA synthesis (UDS) test, or the in vivo rat micronucleus test for mutagenicity. Alosetron at oral doses up to 40 mg/kg/day (about 160 times the recommended daily human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male or female rats.

Brand Names U.S.

  • Lotronex

Pharmacologic Category

  • Selective 5-HT3 Receptor Antagonist

Special Populations Hepatic Function Impairment

Exposure to alosetron is increased.

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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 Risk Factor B Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Alosetron should be used in pregnant women only if clearly needed.

In Summary

Commonly reported side effects of alosetron include: constipation. See below for a comprehensive list of adverse effects.

Liver Dose Adjustments

-Mild or moderate hepatic impairment (Child-Pugh score 9 or less): Use with caution.
-Severe hepatic impairment (Child-Pugh score greater than 9): Contraindicated.

Precautions

US REMS: The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for this drug. It includes a medication guide, elements to assure safe use, and an implementation system. For additional information: www.fda.gov/REMS.

US BOXED WARNING:
SERIOUS GASTROINTESTINAL ADVERSE REACTIONS:
-Infrequent but serious gastrointestinal adverse reactions have been reported with the use of this drug. These events (including ischemic colitis and serious complications of constipation) have resulted in hospitalization, and rarely, blood transfusion, surgery, and death.
-Only healthcare providers who have enrolled in the REMS program should prescribe this drug.
-This drug is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have not responded adequately to conventional therapy.
-This drug should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Treatment should be permanently discontinued in patients with ischemic colitis, but it may be resumed in patients with resolved constipation on the advice of their prescriber.

Safety and efficacy have not been established in patients younger than 18 years. Use is not recommended in the pediatric population based upon the serious complications or constipation and ischemic colitis in adults.

Consult WARNINGS section for additional precautions.

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