Alosetron
Sources réglementaires consultées
Indications approuvées
- Uniquement chez les femmes atteintes d'un syndrome de l'intestin irritable sévère à prédominance diarrhéique, avec symptômes chroniques, évaluation gastro-intestinale appropriée et réponse insuffisante au traitement conventionnel.
Contre-indications
Absolues
- Constipation actuelle ou antécédent de constipation chronique ou sévère et de ses séquelles.
- Antécédent de colite ischémique, obstruction ou perforation intestinale, mégacôlon toxique, maladie de Crohn, rectocolite hémorragique ou diverticulite.
- Circulation intestinale altérée, thrombophlébite ou état d'hypercoagulabilité.
- Insuffisance hépatique sévère.
- Utilisation concomitante de fluvoxamine.
Mises en garde cliniques
- Mise en garde encadrée · Il peut provoquer une colite ischémique et des complications graves de la constipation, pouvant nécessiter une hospitalisation ou une chirurgie, voire entraîner le décès. La notice indique un arrêt immédiat par l'équipe soignante en cas de constipation ou de signes de colite ischémique; il ne doit pas être repris après une colite ischémique. — FDA label
Interactions médicamenteuses
- SévèreFluvoxamineN06AB08
Mécanisme: L'inhibition puissante du CYP1A2 augmente d'environ 6 fois l'exposition à l'alosétron et prolonge sa demi-vie.
Recommandation: L'utilisation concomitante est contre-indiquée selon la notice.
FDA label
Effets indésirables
Communs (≥1%)
Constipation
Rares mais graves
Colite ischémique · Obstruction ou perforation intestinale
Bibliographie récente (PubMed)
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with significant disease burden. This American Gastroenterological Association Guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS with predominant diarrhea (IBS-D) and is an update of a prior technical review and guideline. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: eluxadoline, rifaximin, alosetron, loperamide, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The guideline panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. The panel agreed on 8 recommendations for the management of patients with IBS-D. The panel made conditional recommendations for eluxadoline, rifaximin, alosetron, (moderate certainty), loperamide (very low certainty), tricyclic antidepressants, and anstispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).
Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr.
Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction, characterized by recurrent abdominal pain in association with more frequent, loose stools. The pathophysiology of irritable bowel syndrome (IBS) includes disordered gut motility, alterations in gut microbiota, neural-hormonal system abnormalities, immune reactivity, and visceral hypersensitivity. Timely diagnosis of IBS-D can be achieved easily using clinical criteria. Formal IBS diagnosis is important for optimizing treatment and patient outcomes and facilitating patient access to appropriate educational resources. Yet, given the symptom overlap with other gastrointestinal conditions, diagnosis of IBS-D often is perceived to be challenging. Treatment of IBS includes both nonpharmacologic and pharmacologic options. Rifaximin, alosetron, and eluxadoline are effective treatments indicated for IBS-D, but have limited availability internationally. Dietary approaches may also be indicated for certain patients with IBS-D. Psychological interventions may be effective in treating abdominal pain alone and global symptoms in IBS. We describe use of these diverse therapies and provide an overview to facilitate the primary care provider's approach to distinguishing IBS-D from other conditions with symptom overlap.
Understanding the safety of pharmacotherapy for irritable bowel syndrome (IBS) enables individuals to make informed treatment decisions. While many studies include the number needed to treat to highlight therapeutic benefits, adding the number needed to harm (NNH), a measure we evaluate herein, could enable more comprehensive risk-benefit assessments. PubMed, Web of Science, and Cochrane databases were searched through October 2024. Clinical trials investigating IBS pharmacotherapies including discontinuation rates because of adverse events (AEs) were included. Data were pooled using a random-effects model. The primary outcome was NNH for each pharmacotherapy, defined as the reciprocal of the absolute difference in risk of AEs leading to treatment discontinuation between the experimental and placebo groups. Secondary outcomes included the relative risk of withdrawing because of an AE and the most common AEs for each drug. Fifty-four trials met inclusion criteria. For constipation-predominant IBS pharmacotherapies, the NNH for linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor was 35 ( P < 0.01), 53 ( P = 0.59), 59 ( P < 0.01), 58 ( P = 0.03), and 16 ( P < 0.01), respectively. For diarrhea-predominant IBS pharmacotherapies, the NNH for alosetron and eluxadoline was 14 ( P < 0.01) and 32 ( P < 0.01) whereas the NNH for both rifaximin and ramosetron was a negative, although statistically insignificant, value. For IBS global symptom pharmacotherapies, the tricyclics, the NNH was 24 ( P < 0.01). Many AEs were transient without long-term sequela. Among pharmacotherapies for IBS, tricyclics (especially at elevated doses), tenapanor, and alosetron have the highest absolute risk of discontinuation because of an AE when compared with rifaximin, the safest pharmacotherapy studied.
Irritable bowel syndrome (IBS), which presents a significant healthcare and socioeconomic burden, is one of the main issues in the field of therapy. Hence, it is imperative to tackle this matter by evaluating the safety and efficacy of the available treatments and determining the ideal approach for each patient. We reviewed the pharmacokinetics and safety of pharmacologic interventions administered in diarrhea-predominant IBS (IBS-D) patients. PubMed, Google Scholar and the USFDA databases were searched up to November 2023 to include all updated information on eluxadoline, alosetron, and rifaximin. The most effective way to treat IBS-D is to focus on managing the most common symptoms. However, healthcare providers face a challenge when it comes to identifying the right treatment for each patient, and the root cause of this is the diversity of IBS-D population. Studies have shown that there are differences in how men and women metabolize drugs, which may lead to gender-specific adverse reactions. Women tend to have higher drug concentrations in their bloodstream and take longer to eliminate them. Therefore, healthcare providers may need to reduce the dosage for female patients. Integrating IBS care into sustainable development efforts can indirectly contribute to achieving SDGs and promote health and well-being for all.