Alosetron hydrochloride

330.81

330.124725

1312995-182-4

2F5R1A46YW

DTXSID8044208

C47386

2933790002

53.9

3.14820

white to beige

1.34g/cm3

288-291 °C

648.1ºC at 760 mmHg

345.8ºC

H2O: ≥5mg/mL at warmed

Refrigerator

1.1E-16mmHg at 25°C

Mol wt: 294.35. /Alosetron/

UN 2811 6.1 / PGIII

3

25-36-52/53

26-45

T,Xi

P273-P301 + P310-P305 + P351 + P338

H301-H319-H411

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl alosetron hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P273, P280, P301+P310, P305+P351+P338, P321, P330, P337+P313, P405, and P501|Aggregated GHS information provided by 42 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

... /A study was conducted/ to examine the potential for alosetron to alter the pharmacokinetics of theophylline by inhibiting its metab, as suggested by in vitro & in vivo effects on CYP1A2 activity. ... Ten healthy female volunteers received theophylline 200 mg twice daily alone for 8 days & with alosetron 1 mg twice daily for 15 days in this randomized, placebo-controlled, two-way-crossover study. ... Alosetron had no significant effect on theophylline plasma concns (Cmax approx 9 microg/ml), AUC approx 90 microg/ml-hr) or oral formation clearance of 3 major metabolites produced via CYP1A2: 3-methylxanthine, 1-methylurate & 1,3-dimethylurate (5, 7 & 16 ml/min, respectively). Concomitant admin of alosetron & theophylline was well tolerated. ... The absence of a clinical drug interaction involving inhibition of theophylline metab by alosetron was not predicted by in vitro & in vivo metabolic probe data. /Salt not specified/|Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for the treatment of irritable bowel syndrome (IBS) in females whose predominant bowel habit is diarrhea. Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP2C9 & CYP3A4. Fluoxetine is an antidepressant that is administered as a racemic mixture of equipotent R- & S-enantiomers. Fluoxetine metab involves CYP2D6 & CYP2C9 in the formation of its major metabolite, norfluoxetine. This metabolite is also present as two enantiomers, of which only the S-enantiomer exhibits comparable antidepressant activity. This study was conducted to assess the potential for an effect of alosetron on the pharmacokinetics of fluoxetine. This was an open-label, two-period, nonrandomized, crossover study in 12 healthy female & male volunteers. The pharmacokinetics for both enantiomers of fluoxetine & norfluoxetine were examined following single oral doses of 20 mg fluoxetine, given alone & in combination with alosetron 1 mg twice daily for 15 days. The results showed small delays in peak concn but no clinically significant effect of alosetron on the pharmacokinetics of S- & R-fluoxetine or S- & R-norfluoxetine. Coadministration of alosetron & fluoxetine was well tolerated by all subjects.|Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for the treatment of irritable bowel syndrome (IBS) in females whose predominant bowel habit is diarrhea. Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP 2C9 & 3A4. Alprazolam is a short-acting benzodiazepine commonly prescribed for the treatment of anxiety disorders & a potential comedication in patients with IBS. Alprazolam is extensively metabolized by CYP3A4. This clinical study was conducted to assess the potential for a metabolic drug interaction between these two CYP3A4 substrates. This was an open-label, randomized, two-period, crossover study in 12 healthy female & male volunteers to determine the effect of concomitant admin of alosetron at the recommended dose of 1 mg /orally/ bid on the pharmacokinetics of alprazolam following a single oral 1 mg dose. The results showed no effect of alosetron on the pharmacokinetics of alprazolam. Mean alprazolam AUC was 210 & 202 ng/h/ml in the absence & the presence of alosetron, respectively. Therefore, alprazolam may be safely coadministered with alosetron without the need for dosage adjustment.

Alosetron, a selective 5-HT3-receptor antagonist, is indicated for the treatment of irritable bowel syndrome in female patients whose predominant symptom is diarrhea. /Salt not specified/|... Animal models have shown it to be active in anxiety, psychosis, cognitive impairment, emesis & drug withdrawal, though its application in humans has been almost entirely restricted to irritable bowel syndrome (IBS). ... Alosetron appears promising in the treatment of abdominal pain & discomfort & normalising of bowel function in patients with non-constipated IBS. It also improves quality of life, has a high degree of tolerability & has an excellent safety profile to date. /Salt not specified/

Plasma concentrations of alosetron are 30 to 50% lower in men than in women given the same oral dose. In patients with irritable bowel syndrome, concentrations of alosetron are influenced by gender. Efficacy has not been established in men at any dose. /Salt not specified/|/Alosetron/ should not be used in irritable bowel syndrome patients currently constipated or whose predominant bowel symptom in constipation because constipation is a frequent side effect of alosetron. /Salt not specified/|... Constipation is the most frequent adverse event, with a higher incidence of transient constipation in alosetron-treated patients, typically occurring in the first month of treatment. /Salt not specified/|Significant side effects have been noted with the use of alosetron including severe constipation, fecal impaction, & ischemic colitis. ...A case of ischemic colitis in a male patient with IBS who was briefly treated with alosetron /is described/. Clinical, endoscopic, & pathologic features of the focal colitis strongly suggested ischemia. Symptoms correlated temporally with alosetron use, & symptoms abated with discontinuation of the drug. Endoscopic & pathologic resolution of the colitis were documented. /salt not specified/

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. (See all compounds classified as Serotonin Antagonists.)|Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)

Absorption is rapid and ranges from 30 to > 90% after oral administration. /Salt not specified/|Alosetron ... is absorbed rapidly after oral admin & is widely distributed throughout tissues after oral or iv. dosing in animals. Its metab is rapid & extensive with N-demethylation, hydroxylation & oxidation. The drug, or its two principal metabolites, is equally excreted through the biliary tract & kidneys. Alosetron has proved safe in a range of toxicity studies; at high repeated dosing, clinical signs were transient & repeated admin produced no significant adverse effects on fertility, reproductive performance or fetal development. In pharmacokinetic studies, bioavailability of alosetron in healthy volunteers is approx 60% & the plasma half-life is about 1.5 hr. There are some gender differences in the pharmacokinetic profile, with 30-50% higher alosetron concns in females. No consistent differences in alosetron serum concns between the young & elderly were observed. The pharmacokinetics of single, oral doses of alosetron are linear up to 8 mg. ... /Salt not specified/

/Alosetron/ metab is rapid & extensive with N-demethylation, hydroxylation & oxidation. The drug, or its two principal metabolites, is equally excreted through the biliary tract & kidneys. Alosetron has proved safe in a range of toxicity studies; at high repeated dosing, clinical signs were transient & repeated admin produced no significant adverse effects on fertility, reproductive performance or fetal development. ... /Salt not specified/|Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP2C9 & CYP3A4.

Plasma half life is about 1.5 hours.

Serotonin 5HT3-receptor antagonist /Salt not specified/|... 5-HT3 antagonists delay colonic transit, incr colonic compliance, & incr small intestinal water absorption. ... /Salt not specified/|Alosetron (Lotronex) is a potent, highly selective 5-HT(3) antagonist. ... /Salt not specified/

2,3,4,5-tetrahydro-5-methyl-2-((5-methylimidazol-4-yl)methyl)-1H-pyrido(4,3-b)indol-1-one monohydrochloride

The main ingredient in the drug Lotronex ... (tablets)

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients