trospium
Sources réglementaires consultées
Indications approuvées
- Vessie hyperactive avec incontinence par impériosité, urgence et fréquence urinaires.
Contre-indications
Absolues
- Rétention urinaire ou gastrique, glaucome à angle fermé non contrôlé ou hypersensibilité.
Mises en garde cliniques
- Mise en garde majeure · Surveiller la rétention urinaire ou gastrique, le glaucome contrôlé, la somnolence et l’angio-œdème potentiellement mortel. — FDA/DailyMed, set_id 048b4bc7-c77e-40fc-9bfb-bb35c6a3f871
- Mise en garde majeure · L’exposition augmente en cas d’insuffisance rénale ; utiliser le schéma réduit en cas d’atteinte sévère et surveiller les réactions anticholinergiques même en cas d’atteinte modérée. — FDA/DailyMed, set_id 048b4bc7-c77e-40fc-9bfb-bb35c6a3f871
- Mise en garde majeure · Utiliser avec prudence en cas d’insuffisance hépatique modérée ou sévère ; l’exposition en cas d’atteinte hépatique sévère n’a pas été caractérisée. — FDA/DailyMed, set_id 048b4bc7-c77e-40fc-9bfb-bb35c6a3f871
Interactions médicamenteuses
- ModéréeMédicaments éliminés par sécrétion tubulaire active
Mécanisme: La compétition rénale peut augmenter le trospium ou le médicament associé.
Recommandation: Surveiller étroitement les concentrations ou la toxicité.
FDA/DailyMed, set_id 048b4bc7-c77e-40fc-9bfb-bb35c6a3f871https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=048b4bc7-c77e-40fc-9bfb-bb35c6a3f871
- ModéréeAutres antimuscariniques
Mécanisme: Ils augmentent les effets anticholinergiques.
Recommandation: Éviter la charge cumulative et surveiller.
FDA/DailyMed, set_id 048b4bc7-c77e-40fc-9bfb-bb35c6a3f871https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=048b4bc7-c77e-40fc-9bfb-bb35c6a3f871
Effets indésirables
Communs (≥1%)
Sécheresse buccale · Constipation · Céphalées · Dyspepsie
Rares mais graves
Rétention urinaire · Angio-œdème ou anaphylaxie · Confusion ou hallucinations
Grossesse et allaitement
Utiliser pendant la grossesse uniquement si le bénéfice justifie le risque. L’allaitement nécessite une évaluation clinique.
Bibliographie récente (PubMed)
A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. To evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia. EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significa
New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at we
Up to 40% of men older than 50 years have lower urinary tract symptoms, including urinary urgency, nocturia, and weak urinary stream, due to disorders of the bladder and prostate. These symptoms negatively affect quality of life and may be associated with urinary retention, which can cause kidney insufficiency, bladder calculi, hematuria, and urinary tract infections. In men, lower urinary tract symptoms can be caused by bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), an overactive bladder detrusor (a syndrome of urinary urgency and frequency), or both. Behavioral therapy, including pelvic floor physical therapy, timed voiding (voiding at specific intervals), and fluid restriction, can improve symptoms. Medications including α-blockers (such as tamsulosin), 5α-reductase inhibitors (such as finasteride), and phosphodiesterase 5 inhibitors (such as tadalafil) improve lower urinary tract symptoms (mean improvement, 3-10 points on the International Prostate Symptom Score [IPSS], which ranges from 0-35, with higher scores indicating greater severity) and can prevent symptom worsening measured by increased IPSS greater than or equal to 4 points or development of secondary sequelae, such as urinary retention. Combination therapies are more effective than monotherapy. For example, α-blockade (eg, tamsulosin) combined with 5α-reductase inhibition (eg, finasteride) lowers progression risk to less than 10% compared with 10% to 15% with monotherapy. Treatment for overactive bladder detrusor muscle, including anticholinergics (eg, trospium) and β3 agonists (eg, mirabegron), reduces voiding frequency by 2 to 4 times per day and reduces episodes of urinary incontinence by 10 to 20 times per week. Surgery (eg, transurethral resection of the prostate, holmium laser enucleation of the prostate) and minimally invasive surgery are highly effective for refractory or complicated cases of BPH, defined as persistent symptoms despite behavioral and pharmacologic
Schizophrenia is a chronic and severe mental illness associated with substantial morbidity and mortality. Antipsychotics primarily rely on direct dopamine blockade, leading to potential life-interfering adverse events. The purpose of this review is to describe the safety and efficacy of xanomeline-trospium (CobenfyTM), a Food and Drug Administration approved treatment for schizophrenia in adults. Xanomeline has a novel mechanism of action for the treatment of schizophrenia acting as a dual muscarinic-1 and muscarinic-4 preferring receptor agonist. Two phase 3 trials with a xanomeline- trospium up to 125 mg/30 mg 2 times daily for patients with schizophrenia saw significant reductions in PANSS positive and negative subscales, PANSS Marder negative factors, and CGI-S scale scores compared to placebo. The Cohen's d effect for the primary endpoint was around 0.60 in both trials. The medication was well-tolerated in all clinical trials with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with xanomeline-trospium showed that after 52 weeks of treatment more than 75% of participants achieved a > 30% improvement on PANSS total score with a mean decrease in score by 33.3 points. Other improvements were reductions in PANSS positive and negative subscales, PANSS Marder negative factor score, and CGI-S score. In both long-term studies, patients previously in the placebo groups during either phase 2 or phase 3 trials achieved a statistically significant improvement on all efficacy measures starting at week 2. These data suggest that xanomeline-trospium is an effective and well tolerated treatment for schizophrenia with a novel mechanism of action.