Alosetron hydrochloride (Lotronex) for irritable bowel syndrome
- Michael Camilleri, MD
Michael Camilleri, MD
- Professor of Medicine, Pharmacology, and Physiology
- Mayo Clinic College of Medicine
Alosetron hydrochloride is a selective 5-HT3 antagonist that has been approved for the treatment of women with severe diarrhea-predominant irritable bowel syndrome (IBS) who failed to respond to conventional treatment. The drug has been reintroduced to the market after being withdrawn due to adverse effects including severe constipation and ischemic colitis. Communications from the US Food and Drug Administration (FDA) suggest that fewer than 5 percent of patients with IBS are considered to have severe disease, have symptoms that last more than six months and curtail daily activities, and that only a fraction of these have diarrhea-predominant symptoms. Thus, the proportion of IBS patients who will be eligible for alosetron is small.
Physicians who wish to prescribe alosetron are required to:
●Self-attest to their qualifications
●Agree to educate patients on the risks and benefits of treatment and provide patients a copy of the FDA-approved medication guide
●Obtain a written agreement from patients before their initial prescription
- Mayer EA, Berman S, Derbyshire SW, et al. The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients. Aliment Pharmacol Ther 2002; 16:1357.
- Berman SM, Chang L, Suyenobu B, et al. Condition-specific deactivation of brain regions by 5-HT3 receptor antagonist Alosetron. Gastroenterology 2002; 123:969.
- Kozlowski CM, Green A, Grundy D, et al. The 5-HT(3) receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinal c-fos expression in the anaesthetised rat. Gut 2000; 46:474.
- Jarcho JM, Chang L, Berman M, et al. Neural and psychological predictors of treatment response in irritable bowel syndrome patients with a 5-HT3 receptor antagonist: a pilot study. Aliment Pharmacol Ther 2008; 28:344.
- Clemens CH, Samsom M, Van Berge Henegouwen GP, et al. Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers. Aliment Pharmacol Ther 2002; 16:993.
- Viramontes BE, Camilleri M, McKinzie S, et al. Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2001; 96:2671.
- Camilleri M, Atanasova E, Carlson PJ, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology 2002; 123:425.
- Hirata T, Keto Y, Nakata M, et al. Effects of serotonin 5-HT(3) receptor antagonists on CRF-induced abnormal colonic water transport and defecation in rats. Eur J Pharmacol 2008; 587:281.
- D'Souza DL, Dimmitt DC, Robbins DK, et al. Effect of alosetron on the pharmacokinetics of fluoxetine. J Clin Pharmacol 2001; 41:455.
- D'Souza DL, Levasseur LM, Nezamis J, et al. Effect of alosetron on the pharmacokinetics of alprazolam. J Clin Pharmacol 2001; 41:452.
- Koch K, Campanella C, Baidoo CA, et al. Pharmacodynamics and pharmacokinetics of oral contraceptives co-administered with alosetron (Lotronex). Dig Dis Sci 2004; 49:1244.
- Bardhan KD, Bodemar G, Geldof H, et al. A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2000; 14:23.
- Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999; 13:1149.
- Camilleri M, Northcutt AR, Kong S, et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000; 355:1035.
- Camilleri M, Chey WY, Mayer EA, et al. A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome. Arch Intern Med 2001; 161:1733.
- Jones RH, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999; 13:1419.
- Cremonini F, Nicandro JP, Atkinson V, et al. Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea-predominant IBS. Aliment Pharmacol Ther 2012; 36:437.
- Camilleri M, Choi MG. Review article: irritable bowel syndrome. Aliment Pharmacol Ther 1997; 11:3.
- Klein KB. Controlled treatment trials in the irritable bowel syndrome: a critique. Gastroenterology 1988; 95:232.
- Ladabaum U. Safety, efficacy and costs of pharmacotherapy for functional gastrointestinal disorders: the case of alosetron and its implications. Aliment Pharmacol Ther 2003; 17:1021.
- Lembo T, Wright RA, Bagby B, et al. Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2001; 96:2662.
- Wolfe SG, Chey WY, Washington MK, et al. Tolerability and safety of alosetron during long-term administration in female and male irritable bowel syndrome patients. Am J Gastroenterol 2001; 96:803.
- Watson ME, Lacey L, Kong S, et al. Alosetron improves quality of life in women with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2001; 96:455.
- Lembo AJ, Olden KW, Ameen VZ, et al. Effect of alosetron on bowel urgency and global symptoms in women with severe, diarrhea-predominant irritable bowel syndrome: analysis of two controlled trials. Clin Gastroenterol Hepatol 2004; 2:675.
- Krause R, Ameen V, Gordon SH, et al. A randomized, double-blind, placebo-controlled study to assess efficacy and safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant IBS. Am J Gastroenterol 2007; 102:1709.
- Andresen V, Montori VM, Keller J, et al. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol 2008; 6:545.
- Chey WD, Chey WY, Heath AT, et al. Long-term safety and efficacy of alosetron in women with severe diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2004; 99:2195.
- Ford AC, Brandt LJ, Young C, et al. Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol 2009; 104:1831.
- Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials. Clin Ther 2008; 30:884.
- Chang L, Ameen VZ, Dukes GE, et al. A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS. Am J Gastroenterol 2005; 100:115.
- Chang L, Chey WD, Harris L, et al. Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post-marketing surveillance data. Am J Gastroenterol 2006; 101:1069.
- Tong K, Nicandro JP, Shringarpure R, et al. A 9-year evaluation of temporal trends in alosetron postmarketing safety under the risk management program. Therap Adv Gastroenterol 2013; 6:344.
- Chey WD, Cash BD. Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. Expert Opin Investig Drugs 2005; 14:185.
- Higgins PD, Davis KJ, Laine L. Systematic review: the epidemiology of ischaemic colitis. Aliment Pharmacol Ther 2004; 19:729.
- Greenson JK, Stern RA, Carpenter SL, Barnett JL. The clinical significance of focal active colitis. Hum Pathol 1997; 28:729.
- Reed DE, Vanner SJ. Long vasodilator reflexes projecting through the myenteric plexus in guinea-pig ileum. J Physiol 2003; 553:911.
- Painsipp E, Shahbazian A, Holzer P. Alosetron, cilansetron and tegaserod modify mesenteric but not colonic blood flow in rats. Br J Pharmacol 2009; 158:1210.
- Emmanuel AV, Kamm MA. Laser Doppler flowmetry as a measure of extrinsic colonic innervation in functional bowel disease. Gut 2000; 46:212.
- Kvietys PR, Miller T, Granger DN. Intrinsic control of colonic blood flow and oxygenation. Am J Physiol 1980; 238:G478.
- Kvietys PR, Barrowman JA, Harper SL, Granger DN. Relations among canine intestinal motility, blood flow, and oxygenation. Am J Physiol 1986; 251:G25.
- Bampton PA, Dinning PG, Kennedy ML, et al. Spatial and temporal organization of pressure patterns throughout the unprepared colon during spontaneous defecation. Am J Gastroenterol 2000; 95:1027.
- Dinning PG, Bampton PA, Andre J, et al. Abnormal predefecatory colonic motor patterns define constipation in obstructed defecation. Gastroenterology 2004; 127:49.
- Camilleri M. Is there an experimental basis for the development of ischaemic colitis as a result of 5-HT3 antagonist treatment? Neurogastroenterol Motil 2007; 19:77.
- Grundy D, McLean P, Stead R. Impact of 5-HT3 receptor blockade on colonic haemodynamic responses to ischaemia and reperfusion in the rat. Neurogastroenterol Motil 2007; 19:607.