Alosetron

Alosetron comes as a tablet to take by mouth. It is usually taken twice a day with or without food. Take alosetron at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take alosetron exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor will probably start you on a low dose of alosetron. Your doctor will want to talk to you after you have taken the low dose for 4 weeks. If your symptoms are not controlled but you are not experiencing serious side effects of alosetron, your doctor may increase your dose. If you take the increased dose for 4 weeks and your symptoms are still not controlled, alosetron is not likely to help you. Stop taking alosetron and call your doctor.

Alosetron may control IBS but will not cure it. If alosetron helps you and you stop taking it, your IBS symptoms may return within 1 or 2 weeks.

Before taking alosetron,

• tell your doctor and pharmacist if you are allergic to alosetron, any other medications, or any of the ingredients in alosetron tablets. Ask your pharmacist for a list of the ingredients..
• tell your doctor if you are taking fluvoxamine (Luvox) or the medications listed in the IMPORTANT WARNING section, Your doctor will probably tell you not to take alosetron if you are taking one or more of these medications.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), and voriconazole (Vfend); cimetidine (Tagamet); clarithromycin (Biaxin, in Prevpac); fluoroquinolone antibiotics including ciprofloxacin (Cipro), gatifloxacin (Tequin), levofloxacin (Levaquin), norfloxacin (Noroxin), ofloxacin (Floxin), others; hydralazine (apresoline); isoniazid (INH, Nydrazid); certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), saquinavir (Fortovase, Invirase), and tipranavir (Aptivus); procainamide (Procanbid, Pronestyl); and telithromycin (Ketek). Many other medications may also interact with alosetron, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had the conditions listed in the IMPORTANT WARNING section or any stomach or bowel problems, surgery to your stomach or bowels, or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking alosetron, call your doctor.

Unless your doctor tells you otherwise, continue your normal diet.

Do not take a missed dose when you remember it. Skip the missed dose and take the next dose at the regularly scheduled time. Do not take a double dose to make up for a missed one.

Some patients have developed serious bowel side effects while taking alosetron. Serious bowel (intestine) side effects can happen suddenly, including the following.

Serious complications of constipation: About 1 out of every 1,000 women who take alosetron may get 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.
To lower your chances of getting serious complications of constipation, do the following:

• If you are constipated, do not start taking alosetron.
• If you get constipated while taking alosetron, stop taking it right away and call your doctor.
• If your constipation does not get better after stopping alosetron, call your doctor again.
• If you stopped taking alosetron, do not start taking alosetron again unless your doctor tells you to do so.

Ischemic colitis (reduced blood flow to the bowel): About 3 out of every 1,000 women who take alosetron over a 6-month period may get a serious problem where blood flow to parts of the large bowel is reduced. This is called ischemic colitis. The chance of getting ischemic colitis when you take alosetron 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.
To lower your chances of getting serious complications of ischemic colitis, stop taking alosetron and call your doctor right away if you get:

• new or worse pain in your stomach area (abdomen) or
• blood in your bowel movements.

Constipation is the most common side effect among women with IBS who take alosetron. 

If you take too much alosetron, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Dosage Forms & Strengths

tablet

• 0.5mg
• 1mg

Irritable Bowel Syndrome

Indicated only for women with severe diarrhea-predominant IBS who have: chronic IBS symptoms (generally lasting 6 months or longer), had anatomic or biochemical abnormalities of GI tract excluded, and not responded adequately to conventional therapy

Initial 0.5 mg PO q12hr for 4 weeks; if well tolerated, but inadequate control of IBS symptoms, increase up to 1 mg q12hr; discontinue if no improvement after 4 weeks

Renal Impairment

Dose adjustment not studied in the manufacturer's labeling

Hepatic Impairment

Moderate impairment (Child-Pugh score < 9): Use caution

Severe dysfunction (Child-Purgh score ≥ 10): Contraindicated

Not recommended

>10%

Constipation (29%)

1-10%

Abdominal pain (7%)

Nausea (6%)

Headache (≥3%)

GI discomfort and pain (5%)

Fatigue (≥3%)

Gastroenteritis (>3%)

Abdominal distention (2%)

Flatulence (1-3%)

Regurgitation and reflux (2%)

Abdominal distension (2%)

Hemorrhoids (2%)

Urinary tract infection (≥3%)

Muscle spasm (≥3%)

Cough (≥3%)

Nasopharyngitis (≥3%)

<1%

Ischemic colitis

Anxiety

Bone pain

Colitis

Diverticulitis

Cholecystitis

GI impaction

GI spasms

GI ulceration

Alosetron blocks the action of a chemical called serotonin in the intestines. This slows the movement of stools (bowel movements) through the intestines.

Alosetron is used to treat severe, chronic irritable bowel syndrome (IBS) in women who have had diarrhea as the main symptom for at least 6 months. Alosetron should be used only by women who have tried other IBS treatments without success. Alosetron has not been shown to be effective in men with IBS.

Alosetron is not a cure for irritable bowel syndrome. After you stop taking this medicine, your symptoms may return within 1 week.

Alosetron may also be used for purposes not listed in this medication guide.

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.

• It is used to treat irritable bowel syndrome.

• If you have an allergy to alosetron or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have hard stools (constipation).
• If you have ever had any of these health problems: Blood clots or blood-clotting problems, blood flow problems in the bowel, bowel block, Crohn's disease, diverticulitis, hole in the GI (gastrointestinal) tract, ischemic or ulcerative colitis, a large colon, liver problems, long-term or very hard stools (constipation), or narrowing or growths in the bowel.
• If you are taking fluvoxamine.
• If the patient is a child. Do not give alosetron to a child.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take alosetron with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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%

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.

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.

Applies to alosetron: oral tablet

Along with its needed effects, alosetron may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking alosetron:

• Constipation

• Bloody diarrhea
• new or worsening stomach pain or discomfort
• rectal bleeding

• Abdominal or stomach pain, cramping, or burning
• black, tarry stools
• diarrhea
• fever
• heartburn
• indigestion
• nausea
• vomiting with or without blood or material that looks like coffee grounds

Get emergency help immediately if any of the following symptoms of overdose occur while taking alosetron:

• Clumsiness, unsteadiness, trembling, or other problems with muscle control or coordination
• convulsions (seizures)
• difficulty breathing
• shakiness and unsteady walk
• withdrawn or socially detached behavior

Some side effects of alosetron may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bleeding after bowel movement
• full or bloated feeling
• pressure in the stomach
• swelling of abdominal or stomach area
• uncomfortable swelling around rectal area

• Headache
• skin rash