Alosetron Hcl

Drug overview for ALOSETRON HCL (alosetron hcl):

Generic name: ALOSETRON HCL (al-OH-se-tron)
Drug class: Irritable Bowel Syndrome Agents
Therapeutic class: Gastrointestinal Therapy Agents

Alosetron is a selective inhibitor of type 3 serotonergic (5-HT3) receptors, and thus may modulate serotonin-sensitive GI processes.

No enhanced Uses information available for this drug.

DRUG IMAGES

ALOSETRON HCL 0.5 MG TABLET
ALOSETRON HCL 1 MG TABLET

The following indications for ALOSETRON HCL (alosetron hcl) have been approved by the FDA:

Indications:
Diarrhea predominant irritable bowel syndrome

Professional Synonyms:
Diarrhea predominant IBS
Diarrhea predominant spastic colon

The following dosing information is available for ALOSETRON HCL (alosetron hcl):

Dosing
Administration
ALOSETRON HCL
ALOSETRON HCL

Dosage of alosetron hydrochloride is expressed in terms of alosetron.

For the treatment of severe diarrhea-predominant irritable bowel syndrome (IBS) in women, the recommended initial dosage of alosetron is 0.5 mg twice daily. Data from a dose-ranging study indicate that risk of constipation is reduced with this dosage compared with a dosage of 1 mg twice daily; however, efficacy of the 0.5-mg

twice-daily dosage in women with severe diarrhea-predominant IBS has not been adequately evaluated in clinical studies. If constipation occurs at a dosage of 0.5 mg twice daily, therapy should be withheld until constipation resolves; upon resolution, alosetron may be reinitiated at a reduced dosage of 0.5

mg once daily. If constipation recurs at a dosage of 0.5 mg once daily, treatment with alosetron should be immediately discontinued.

Patients may continue receiving an alosetron dosage of 0.5 mg once or twice daily as maintenance therapy if the dosage is well tolerated and symptoms of IBS are adequately controlled. If the patient tolerates but does not respond adequately to the dosage after 4 weeks, dosage may be increased up to 1 mg twice daily.

If adequate control of symptoms is not achieved after 4 weeks of treatment on a dosage of 1 mg twice daily, alosetron therapy should be discontinued.

Alosetron should be discontinued immediately and permanently in patients who develop ischemic colitis. (See Ischemic Colitis under Warnings/Precautions: Warnings, in Cautions.)

If a dose of alosetron is missed, the dose should be skipped and the next dose should be taken at the regularly scheduled time. A double dose should not be taken to make up for the missed dose.

No enhanced Administration information available for this drug.

Dosing information for ALOSETRON HCL
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
ALOSETRON HCL 0.5 MG TABLET	Maintenance	Adults take 1 tablet (0.5 mg) by oral route 2 times per day
ALOSETRON HCL 1 MG TABLET	Maintenance	Adults take 1 tablet (1 mg) by oral route once daily

Generic dosing information for ALOSETRON HCL
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
ALOSETRON HCL 0.5 MG TABLET	Maintenance	Adults take 1 tablet (0.5 mg) by oral route 2 times per day
ALOSETRON HCL 1 MG TABLET	Maintenance	Adults take 1 tablet (1 mg) by oral route once daily

The following drug interaction information is available for ALOSETRON HCL (alosetron hcl):

Contraindicated
Severe
Moderate

There are 3 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Alosetron/Fluvoxamine SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Fluvoxamine may inhibit the metabolism of alosetron at CYP1A2 and CYP3A4.(1,2) CLINICAL EFFECTS: Concurrent administration with fluvoxamine may result in 6-fold increases in alosetron levels and toxicity.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturers of alosetron(1) and fluvoxamine(2) state that concurrent use is contraindicated. DISCUSSION: In a study in 40 healthy females, pretreatment with fluvoxamine (escalating doses from 50 mg to 200 mg daily for 16 days) increased the area-under-curve (AUC) and half-life of alosetron by 6-fold and 3-fold, respectively.(1,2)	FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER
Apomorphine/Selected 5-HT3 Antagonists SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The mechanism for risk of profound hypotension or loss of consciousness is not known. CLINICAL EFFECTS: Concurrent use of apomorphine with a 5-HT3 antagonist may result in profound hypotension and loss of consciousness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of apomorphine states that concurrent use with 5-HT3 antagonists is contraindicated. Alternative agents, such as trimethobenzamide, are recommended for prevention of nausea and vomiting caused by apomorphine.(3) DISCUSSION: Profound hypotension and loss of consciousness have been reported with the concurrent use of apomorphine and ondansetron.(1,2) Selected 5-HT3 Antagonists linked to this monograph include: alosetron, azasetron, and ramosetron.	APOKYN, APOMORPHINE HCL, ONAPGO
Selected CYP1A2 Substrates/Viloxazine SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Viloxazine is a strong inhibitor of CYP1A2 and may increase the total exposure of sensitive CYP1A2 substrates.(1) The FDA defines strong inhibition as an increase in drug area-under-curve (AUC) greater than 5-fold.(2) CLINICAL EFFECTS: Concurrent use of viloxazine with drugs primarily metabolized by CYP1A2 may lead to elevated drug levels and increase the risk of adverse reactions associated with the CYP1A2 substrate.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Drugs linked to this monograph have a narrow therapeutic window or are sensitive to CYP1A2 inhibition. Coadministration of viloxazine with sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic window is contraindicated.(1) DISCUSSION: Concomitant use of viloxazine significantly increases the total exposure, but not peak exposure, of sensitive CYP1A2 substrates, which may increase the risk of adverse reactions associated with these CYP1A2 substrates. In a study, viloxazine increased the AUC of caffeine by almost 6-fold.(1) CYP1A2 substrates linked to this monograph include: agomelatine, alosetron, aminophylline, duloxetine, ramelteon, tasimelteon, and theophylline.(2,3)	QELBREE

There are 0 severe interactions.

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Tramadol/5-HT3 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The interaction may involve a reduction in the binding involving 5-HT3 receptors.(1) CLINICAL EFFECTS: Concurrent use of 5-HT3 antagonists may decrease the effectiveness of tramadol, resulting in increased use of tramadol.(1-3) 5-HT3 antagonists may not be effective in reducing tramadol-induced nausea.(4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider the use of alternative anti-emetics in patients receiving tramadol, or the use of other opioids in patients receiving 5-HT3 antagonists. DISCUSSION: In a randomized study in 59 post-surgical patients in recovery, compared to tramadol alone, patients receiving concurrent ondansetron required significantly larger doses of tramadol at four hours (223 mg versus 71 mg), at 8 hours (285 mg versus 128 mg), and at 12 hours (406 mg versus 190 mg). Vomiting rates at 4 hours and 8 hours were significantly higher with tramadol and concurrent ondansetron compared to tramadol alone.(1) In a randomized, double-blind study in 40 surgical patients undergoing lumbar laminectomy, compared to tramadol alone, cumulative tramadol consumption with concurrent ondansetron during the first 24 hours was significantly increased (between 26% and 35%) as well as thereafter (22% to 25%).(2) In another randomized study in 120 post-surgical patients, it was discovered that tramadol consumption was increased in those patients receiving concurrent ondansetron compared to tramadol alone.(3) In a prospective, randomized, double-blinded study in dental patients, patients received one of four treatments: fentanyl and metoclopramide, tramadol and metoclopramide, fentanyl and ondansetron, or tramadol and ondansetron. The patients who received tramadol and ondansetron had the highest nausea scores among the treatment groups. There were no significant differences in the incidences of pain or nausea in the 24 hours following the procedure.(4) In a randomized, controlled trial in 40 surgical patients undergoing hernioplasty or thyroidectomy, compared to tramadol alone, cumulative tramadol consumption was higher at the 2-hour time point with concurrent ondansetron (0.24 +/- 0.1 vs. 0.17 +/- 0.16; p = 0.01).(5) A systematic review and meta-analysis of randomized controlled trials in the postoperative setting comparing tramadol alone and in combination with ondansetron were included. At 4-hours, 8-hours, 12-hours, and 24-hours post-procedure, patients had increased tramadol requirements when administered with concurrent ondansetron compared to tramadol alone.(6) 5-HT3 antagonists linked to this monograph include: alosetron, azasetron, dolasetron, granisetron, ondansetron, palonosetron, ramosetron, and tropisetron.	CONZIP, QDOLO, TRAMADOL HCL, TRAMADOL HCL ER, TRAMADOL HCL-ACETAMINOPHEN

Drug Interaction

Drug Names

Tramadol/5-HT3 Antagonists

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The interaction may involve a reduction in the binding involving 5-HT3 receptors.(1)

CLINICAL EFFECTS: Concurrent use of 5-HT3 antagonists may decrease the effectiveness of tramadol, resulting in increased use of tramadol.(1-3) 5-HT3 antagonists may not be effective in reducing tramadol-induced nausea.(4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Consider the use of alternative anti-emetics in patients receiving tramadol, or the use of other opioids in patients receiving 5-HT3 antagonists.

DISCUSSION: In a randomized study in 59 post-surgical patients in recovery, compared to tramadol alone, patients receiving concurrent ondansetron required significantly larger doses of tramadol at four hours (223 mg versus 71 mg), at 8 hours (285 mg versus 128 mg), and at 12 hours (406 mg versus 190 mg). Vomiting rates at 4 hours and 8 hours were significantly higher with tramadol and concurrent ondansetron compared to tramadol alone.(1) In a randomized, double-blind study in 40 surgical patients undergoing lumbar laminectomy, compared to tramadol alone, cumulative tramadol consumption with concurrent ondansetron during the first 24 hours was significantly increased (between 26% and 35%) as well as thereafter (22% to 25%).(2)

In another randomized study in 120 post-surgical patients, it was discovered that tramadol consumption was increased in those patients receiving concurrent ondansetron compared to tramadol alone.(3) In a prospective, randomized, double-blinded study in dental patients, patients received one of four treatments: fentanyl and metoclopramide, tramadol and metoclopramide, fentanyl and ondansetron, or tramadol and ondansetron. The patients who received tramadol and ondansetron had the highest nausea scores among the treatment groups.

There were no significant differences in the incidences of pain or nausea in the 24 hours following the procedure.(4) In a randomized, controlled trial in 40 surgical patients undergoing hernioplasty or thyroidectomy, compared to tramadol alone, cumulative tramadol consumption was higher at the 2-hour time point with concurrent ondansetron (0.24 +/- 0.1 vs. 0.17 +/- 0.16; p = 0.01).(5) A systematic review and meta-analysis of randomized controlled trials in the postoperative setting comparing tramadol alone and in combination with ondansetron were included.

At 4-hours, 8-hours, 12-hours, and 24-hours post-procedure, patients had increased tramadol requirements when administered with concurrent ondansetron compared to tramadol alone.(6) 5-HT3 antagonists linked to this monograph include: alosetron, azasetron, dolasetron, granisetron, ondansetron, palonosetron, ramosetron, and tropisetron.

CONZIP, QDOLO, TRAMADOL HCL, TRAMADOL HCL ER, TRAMADOL HCL-ACETAMINOPHEN

The following contraindication information is available for ALOSETRON HCL (alosetron hcl):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Current constipation, history of chronic or severe constipation, or history of complications related to constipation. History of intestinal obstruction, stricture, toxic megacolon, GI perforation, and/or adhesions. History of ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state.

History of Crohn's disease, ulcerative colitis, or diverticulitis. History of severe hepatic impairment. Concomitant use of fluvoxamine. (See Drug Interactions: Fluvoxamine.)

There are 12 contraindications. Absolute contraindication.

Contraindication List
Adhesion of gastrointestinal tract
Child-pugh class C hepatic impairment
Constipation
Crohn's disease
Diverticulitis of gastrointestinal tract
Gastrointestinal obstruction
Gastrointestinal perforation
Ischemic bowel disease
Thrombophilia
Thrombophlebitis
Toxic megacolon
Ulcerative colitis

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Disease of liver

There are 0 moderate contraindications.

The following adverse reaction information is available for ALOSETRON HCL (alosetron hcl):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects occurring in 2% or more of patients with IBS receiving alosetron in clinical studies include constipation, abdominal discomfort or pain, nausea, GI discomfort or pain, abdominal distention, regurgitation and reflux, and hemorrhoids. In women with severe diarrhea-predominant IBS, diarrhea, hemorrhoidal hemorrhage, and flatulence also were reported in addition to the adverse effects observed in the general IBS population.

There are 21 severe adverse reactions.

More Frequent	Less Frequent
None.	Bleeding hemorrhoids Severe constipation

Rare/Very Rare
Abnormal hepatic function tests Bacterial infection Cardiac arrhythmia Extrasystoles Fecal impaction Gastrointestinal obstruction Gastrointestinal perforation Gastrointestinal ulcer Hyperbilirubinemia Hypertension Hypothalamic-pituitary insufficiency Ileus Intussusception of intestine Ischemic bowel disease Ischemic colitis Tachyarrhythmia Toxic megacolon Ulcerative colitis Urticaria

There are 43 less severe adverse reactions.

More Frequent	Less Frequent
Constipation	Acute abdominal pain Diarrhea Flatulence Upper respiratory infection Urinary tract infection

Rare/Very Rare
Abdominal distension Abnormal sexual function Abnormal vaginal bleeding Acne vulgaris Allergic rhinitis Cough Depression Dysgeusia Dyspepsia Dyspnea Fatigue Folliculitis Gastritis Gastroesophageal reflux disease Headache disorder Hematoma Hemorrhoids Hyperhidrosis Hypnagogic hallucination Hypoesthesia Increased urinary frequency Insomnia Irregular menstrual periods Malaise Nausea Parosmia Pharyngitis Photophobia Polyuria Proctitis Sedation Sinusitis Skin rash Sore throat Symptoms of anxiety Viral infection Xerostomia

Rare/Very Rare

Abdominal distension
Abnormal sexual function
Abnormal vaginal bleeding
Acne vulgaris
Allergic rhinitis
Cough
Depression
Dysgeusia
Dyspepsia
Dyspnea
Fatigue
Folliculitis
Gastritis
Gastroesophageal reflux disease
Headache disorder
Hematoma
Hemorrhoids
Hyperhidrosis
Hypnagogic hallucination
Hypoesthesia
Increased urinary frequency
Insomnia
Irregular menstrual periods
Malaise
Nausea
Parosmia
Pharyngitis
Photophobia
Polyuria
Proctitis
Sedation
Sinusitis
Skin rash
Sore throat
Symptoms of anxiety
Viral infection
Xerostomia

The following precautions are available for ALOSETRON HCL (alosetron hcl):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of alosetron have not been established in pediatric patients younger than 18 years of age. The drug is not recommended for use in the pediatric population because of the risk of serious GI complications.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Category B. (See Users Guide.) There are no adequate and well-controlled studies of alosetron in pregnant women; animal reproduction studies using alosetron doses up to 160-240 times the recommended human dose have not demonstrated any evidence of fetal harm. Alosetron should be used during pregnancy only if clearly needed.

Alosetron and/or its metabolites are distributed into milk in rats; it is not known whether alosetron is distributed into milk in humans. Caution is advised if the drug is administered in nursing women.

In some studies in healthy individuals, plasma concentrations of alosetron were increased by approximately 40% in those 65 years of age or older compared with younger adults. Because of evidence suggesting that geriatric patients may be at greater risk for complications of constipation, alosetron should be used with caution and appropriate follow-up in such patients.

Diarrhea predominant irritable bowel syndrome
K58.0	Irritable bowel syndrome with diarrhea